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J Potter

Publications and source records attributed to J Potter.

At least 19 recordsLinked to original sources

Variants in Apaf-1 segregating with major depression promote apoptosome function.

APAF1, encoding the protein apoptosis protease activating factor 1 (Apaf-1), has recently been established as a chromosome 12 gene conferring predisposition to major depression in humans. The molecular phenotypes of Apaf-1 variants were determined by in vitro reconstruction of the apoptosome complex in which Apaf-1 activates caspase 9 and thus initiates a cascade of proteolytic events leading to apoptotic destruction of the cell. Cellular phenotypes were measured using a yeast heterologous expression assay in which human Apaf-1 and other proteins necessary to constitute a functional apoptotic pathway were overexpressed. Apaf-1 variants encoded by APAF1 alleles that segregate with major depression in families linked to chromosome 12 shared a common gain-of-function phenotype in both assay systems. In contrast, other Apaf-1 variants showed neutral or loss-of-function phenotypes. The depression-associated alleles thus have a common phenotype that is distinct from that of non-associated variants. This result suggests an etiologic role for enhanced apoptosis in major depression.

Alleles↗

Vitamin D deficiency in outpatients:--a Scottish perspective.

UNLABELLED: Vitamin D deficiency is common in older people and increases risk of falls, osteoporosis and fracture. This may be reduced with supplements. Recent Scottish guidelines recommend routine use of vitamin D and calcium for all older housebound, sunlight deprived or institutionalised people. Whilst many outpatients will undoubtedly meet these criteria, others who would benefit may not. We have determined the extent of vitamin D deficiency in older outpatients in our geographical area, to clarify further whether those found to be deficient, would receive supplementation under current guidelines. METHODOLOGY: 102 new patient referrals to outpatient clinics and day hospital were questioned over their social circumstances and activity levels, and had serum 25-Hydroxy Vitamin D (25(OH)D) levels measured in wintertime. RESULTS: Mean age was 79.6 (SD 7.3), 31.4% were housebound and 51.0% exposed their skin to sunlight. 72.6% had insufficient vitamin D levels [25(OH)D < 50 nmol/l], 27.5% of whom levels were frankly deficient [25(OH)D < 25 nmol/l]. Deficiency was significantly more common in females (p = 0.002), those attending the falls clinic or day hospital (p = 0.021), the housebound (p = 0.012) or patients who never exposed their skin to sunlight (p = 0.007). However, even in those patients who were outdoors frequently or who did expose their skin to the sun, the mean vitamin D levels remained insufficient [mean 25(OH)D = 45.6 (SD 26.2) nmol/l and 47.9 (SD 26.3) nmol/l respectively]. CONCLUSIONS: The prevalence of vitamin D deficiency is high in older outpatients in this geographical area. These patients may benefit from routine vitamin D and calcium, but currently many would not be targeted in recent Scottish Executive recommendations because they are not housebound and sunlight deprived.

Aged↗

Protein and energy supplementation in elderly people at risk from malnutrition.

BACKGROUND: Evidence for the effectiveness of nutritional supplements containing protein and energy, which are often prescribed for older people, is limited. Furthermore malnutrition is more common in this age group and deterioration of nutritional status can occur during illness. It is important to establish whether supplementing the diet is an effective way of improving outcomes for older people at risk from malnutrition. OBJECTIVES: This review examined the evidence from trials for improvement in nutritional status and clinical outcomes when extra protein and energy were provided, usually in the form of commercial 'sip-feeds'. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Healthstar, CINAHL, BIOSIS, CAB abstracts. We also hand searched nutrition journals and reference lists and contacted 'sip-feed' manufacturers. Date of most recent search: March 2004. SELECTION CRITERIA: Randomised controlled trials and quasi-randomised controlled trials of oral protein and energy supplementation in older people with the exception of groups recovering from cancer treatment or in critical care. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trials prior to inclusion and independently extracted data and assessed trial quality. Authors of trials were contacted for further information as necessary. MAIN RESULTS: Forty-nine trials with 4790 randomised participants have been included in the review. Most included trials had poor study quality. The pooled weighted mean difference [WMD] for percentage weight change showed a benefit of supplementation of 2.3% (95% confidence interval (CI) 1.9 to 2.7) from 34 trials. There was a reduced mortality in the supplemented compared with control groups (relative risk (RR) 0.74, CI 0.59 to 0.92) from 32 trials. The risk of complications from 14 trials showed no significant difference (RR 0.95, 95% CI 0.81 to 1.11). Few trials were able to suggest any functional benefit from supplementation. The pooled weighted mean difference (WMD) for length of stay from 10 trials also showed no statistically significant effect (WMD -1.98 days, 95% CI -5.20 to 1.24). AUTHORS' CONCLUSIONS: Supplementation produces a small but consistent weight gain in older people. There may also be a beneficial effect on mortality. However, there was no evidence of improvement in clinical outcome, functional benefit or reduction in length of hospital stay with supplements. Additional data from large-scale multi-centre trials are still required.

Aged↗

CHHIPS (Controlling Hypertension and Hypotension Immediately Post-Stroke) Pilot Trial: rationale and design.

RATIONALE: High and low blood pressure (BP) levels are common following acute stroke, with up to 60% of patients being hypertensive (SBP > 160 mmHg) and nearly 20% having relative hypotension (SBP < or = 140 mmHg), within the first few hours of ictus, both conditions being associated with an adverse prognosis. At present, the optimum management of blood pressure in the immediate post-stroke period is unclear. OBJECTIVE: The primary aim of the Controlling Hypertension and Hypotension Immediately Post-Stroke (CHHIPS) Pilot Trial is to assess whether hypertension and relative hypotension, manipulated therapeutically in the first 24 h following acute stroke, affects short-term outcome measures. DESIGN: The CHHIPS Pilot Trial is a UK based multi-centre, randomized, double-blind, placebo-controlled, titrated dose trial. SETTING: Acute stroke and medical units in teaching and district general hospitals, in the UK. PATIENTS: The CHHIPS Pilot Study aims to recruit 2050 patients, with clinically suspected stroke, confirmed by brain imaging, who have no compelling indication or contraindication for BP manipulation. STUDY OUTCOMES: The primary outcome measure will be the effects of acute pressor therapy (initiated < or = 12 h from stroke onset) or depressor therapy (started < or = 24 h post-ictus) on death and dependency at 14 days post-stroke. Secondary outcome measures will include the influence of therapy on early neurological deterioration, the effectiveness of treatment in manipulating BP levels, the influence of time to treatment and stroke type on response and a cost-effectiveness analysis.

Acute Disease↗

Supra-maximal effort and reaction and movement times in a non-compatible response time task.

AIM: The primary purpose of this study was to examine the effect of attempting to exercise supra-maximally on reaction time and movement time in a non-compatible response time task. METHODS: Subjects (n=9) undertook a 4-choice non-compatible response time test at rest, while cycling at 70 rpm with a resistance of 35 W (low intensity exercise), cycling at 70% of their maximum power output (MPO), cycling at 100% MPO and attempting to cycle at 70 rpm, with a resistance that was 28 W greater than the resistance required to elicit MPO (supra-maximal effort). RESULTS: Reaction time, movement time, intra-individual variations in reaction time and movement time at each exercise intensity were compared by a series of repeated measures analyses of variance. A significant effect of exercise was shown for movement time, F(4,32)=6.05, p<0.001, eta2=0.44, Power=0.97 and intra-individual variation in reaction time, F(4,32)=4.98, p<0.005, eta2=0.38, Power=0.93. For movement time, Tukey post-hoc tests showed that performance at rest was significantly slower than that during exercise at 70%, 100% MPO and supra-maximal effort. Performance at low intensity exercise was significantly slower than that at MPO. For intra-individual variations in reaction time, Tukey tests found that variations under supra-maximal effort and MPO were significantly greater than those at low intensity and 70% MPO. CONCLUSIONS: It was concluded that exercise facilitates speed of movement when the limbs used for the motor task are not the ones that are being exercised. Reaction time during maximal and supra-maximal exercise demonstrates large intra-individual variations.

Adult↗

The effectiveness of a modified version of the Wilkinson questionnaire in screening for TIA and minor stroke in the United Kingdom.

BACKGROUND: Transient ischaemic attacks (TIAs) and minor strokes are important to diagnose as there are effective secondary preventive interventions. Significant under-reporting by patients occurs, but general practitioners tend to over-diagnose the condition, contributing in part to long clinic waiting lists. An accurate screening test could address both these problems. METHODS: A modified version of a questionnaire designed to detect TIA was tested against the gold standard of specialist diagnosis in two vascular outpatient clinics in Leicester, UK. RESULTS: The questionnaire was sent by post with the clinic appointment and completed by 136 participants. In 99 cases the same questionnaire was administered by a clinic nurse. Overall levels of agreement (kappa, 95% CI) with specialist diagnosis of TIA, stroke or neither were 0.32 (0.15, 0.48) and 0.31 (0.12, 0.50) for postal and administered questionnaires, respectively. When the diagnoses of TIA and stroke were combined, agreement rose to 0.38 (0.23, 0.53) for postal and 0.38 (0.20, 0.57) for administered versions. For this outcome, the postal version had a sensitivity of 0.56 (0.43, 0.68) and specificity of 0.81 (0.71, 0.90). Equivalent figures for administered questionnaires were 0.61 (0.46, 0.76) and 0.76 (0.63, 0.87). CONCLUSION: The questionnaire has potential in prioritising outpatient referrals but is not sufficiently specific to be used for research or population screening.

Aged↗

Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomised controlled trial.

BACKGROUND: Among patients with substantial carotid artery narrowing but no recent neurological symptom (stroke or transient ischaemia), the balance of surgical risks and long-term benefits from carotid endarterectomy (CEA) was unclear. METHODS: During 1993-2003, 3120 asymptomatic patients with substantial carotid narrowing were randomised equally between immediate CEA (half got CEA by 1 month, 88% by 1 year) and indefinite deferral of any CEA (only 4% per year got CEA) and were followed for up to 5 years (mean 3.4 years). Kaplan-Meier analyses of 5-year risks are by allocated treatment. FINDINGS: The risk of stroke or death within 30 days of CEA was 3.1% (95% CI 2.3-4.1). Comparing all patients allocated immediate CEA versus all allocated deferral, but excluding such perioperative events, the 5-year stroke risks were 3.8% versus 11% (gain 7.2% [95% CI 5.0-9.4], p<0.0001). This gain chiefly involved carotid territory ischaemic strokes (2.7% vs 9.5%; gain 6.8% [4.8-8.8], p<0.0001), of which half were disabling or fatal (1.6% vs 5.3%; gain 3.7% [2.1-5.2], p<0.0001), as were half the perioperative strokes. Combining the perioperative events and the non-perioperative strokes, net 5-year risks were 6.4% versus 11.8% for all strokes (net gain 5.4% [3.0-7.8], p<0.0001), 3.5% versus 6.1% for fatal or disabling strokes (net gain 2.5% [0.8-4.3], p=0.004), and 2.1% versus 4.2% just for fatal strokes (net gain 2.1% [0.6-3.6], p=0.006). Subgroup-specific analyses found no significant heterogeneity in the perioperative hazards or (apart from the importance of cholesterol) in the long-term postoperative benefits. These benefits were separately significant for males and females; for those with about 70%, 80%, and 90% carotid artery narrowing on ultrasound; and for those younger than 65 and 65-74 years of age (though not for older patients, half of whom die within 5 years from unrelated causes). Full compliance with allocation to immediate CEA or deferral would, in expectation, have produced slightly bigger differences in the numbers operated on, and hence in the net 5-year benefits. The 10-year benefits are not yet known. INTERPRETATION: In asymptomatic patients younger than 75 years of age with carotid diameter reduction about 70% or more on ultrasound (many of whom were on aspirin, antihypertensive, and, in recent years, statin therapy), immediate CEA halved the net 5-year stroke risk from about 12% to about 6% (including the 3% perioperative hazard). Half this 5-year benefit involved disabling or fatal strokes. But, outside trials, inappropriate selection of patients or poor surgery could obviate such benefits.

Aged↗

Assessing stroke patients' prospective memory using virtual reality.

There is a dearth of empirical evidence about prospective memory (remembering to perform actions in the future) in stroke patients. A probable reason for this is that it is difficult to perform a realistic and controlled assessment of prospective memory ability in a rehabilitation setting. Virtual reality may provide a solution to this difficulty by allowing prospective memory to be tested in a simulation of a real-life situation whilst retaining a laboratory level of scientific control. This exploratory study assessed the performance of stroke patients and age-matched control participants on event-, time- and activity-based prospective memory retrieval tasks in a personal computer-based virtual environment. Stroke patients were severely impaired at the event- and activity-based tasks compared with age-matched controls, but only marginally impaired at the time-based task. The additional knowledge gained from this form of assessment could direct rehabilitation more effectively towards specific impairments of individual patients.

Aged↗

TYRP1 is associated with dun coat colour in Dexter cattle or how now brown cow?

Tyrosinase related protein 1 (TYRP1), which is involved in the coat colour pathway, was mapped to BTA8 between microsatellites BL1080 and BM4006, using a microsatellite in intron 5 of TYRP1. The complete coding sequence of bovine TYRP1 was determined from cDNA derived from skin biopsies of cattle with various colours. Sequence data from exons 2-8 from cattle with diluted phenotypes was compared with that from non-diluted phenotypes. In addition, full-sib families of beef cattle generated by embryo transfer and half-sib families from traditional matings in which coat colour was segregating were used to correlate TYRP1 sequence variants with dilute coat colours. Two non-conservative amino acid changes were detected in Simmental, Charolais and Galloway cattle but these polymorphisms were not associated with diluted shades of black or red, nor with the dun coat colour of Galloway cattle or the taupe brown colour of Braunvieh and Brown Swiss cattle. However, in Dexter cattle all 25 cattle with a dun brown coat colour were homozygous for a H424Y change. One Dexter that was also homozygous Y434 was red because of an "E+/E+" genotype at MC1R which lead to the production of only phaeomelanin. None of the 70 remaining black or red Dexter cattle were homozygous for Y434. This tyrosine mutation was not found in any of the 121 cattle of other breeds that were examined.

Animals↗

The pathogenesis and management of painful diabetic neuropathy: a review.

Painful diabetic neuropathy has always been a challenging complication of diabetes mellitus. Emerging theories suggest that early dysaesthesia associated with painful neuropathy may act as a marker for the development of the 'at risk' foot, allowing preventative clinical strategies to be undertaken. The mechanisms of neuropathic pain are complex. The authors' intentions are to help members of the diabetes care team better understand and appreciate the diverse symptoms reported by patients. The various treatments available for painful neuropathy are discussed in detail. Robust comparative studies on such treatments are, however, unavailable and the authors have designed a logical approach to management based on best current evidence and their own clinical experience.

Anti-Arrhythmia Agents↗

A systematic review of exercise trials post stroke.

OBJECTIVE: To perform a systematic review of exercise trials post stroke. DESIGN: A systematic review of controlled clinical trials. SEARCH STRATEGY: MEDLINE, EMBASE, CINAHL, Amed, Sports Discus, Cochrane controlled trials register and PEDro were searched for relevant trials. INCLUSION CRITERIA: Studies--randomized or quasi-randomized controlled clinical trials. Participants--Adults of any age with a clinical diagnosis of stroke. Interventions--Any cardiovascular exercise intervention aimed at improving cardiovascular fitness and/or function. OUTCOMES: Impairment: gait speed, strength, endurance, balance, flexibility, tonus and exercise capacity. Disability: global dependency, functional independence. Extended activities of daily living. Quality of life. Death. DATA COLLECTION AND ANALYSIS: Two independent reviewers categorized selected trials, documented the methodological quality and extracted the relevant data. Comparisons of cardiovascular exercise interventions versus no cardiovascular intervention were made. Statistical comparisons were carried out using a random effects model to calculate standardized mean differences. RESULTS: We identified three eligible trials. Small numbers and heterogeneous outcomes limited the analyses and comparisons. Based on the limited data available, we found that cardiovascular exercise post stroke was no better than no exercise with respect to disability, impairment, extended activities of daily living, quality of life and death. CONCLUSION: Insufficient evidence was identified to establish if cardiovascular exercise has a positive effect on disability, impairment, extended activities of daily living, quality of life and case fatality post stroke.

Activities of Daily Living↗

Protein and energy supplementation in elderly people at risk from malnutrition.

BACKGROUND: This review was carried out because evidence for the effectiveness of nutritional supplements containing protein and energy which are often prescribed for elderly people is limited. Furthermore malnutrition is more common in this age group and deterioration of nutritional status can occur during a stay in hospital. It is important to establish whether supplementing the diet with protein and energy is an effective way of improving outcomes for older people at risk from malnutrition. OBJECTIVES: This review examines the evidence from trials for improvement in nutritional status and clinical outcomes when extra protein and energy food were provided, usually in the form of commercial 'sip-feeds'. SEARCH STRATEGY: We searched The Cochrane Library (issue 1, 2001), MEDLINE (1966 to February 2001), EMBASE (1980 to March 2001), Health star (1975 to March 2001), CINAHL (1982 to Jan 2001), BIOSIS (1985 to March 2001) and CAB abstracts (1973 to March 2001). We also hand searched nutrition journals and reference lists and contacted 'sip-feed' manufacturers. Date of most recent search: March 2001. SELECTION CRITERIA: Randomised controlled trials and quasi-randomised controlled trials of oral protein and energy supplementation in older people with the exception of groups recovering from cancer treatment or in critical care. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trials prior to inclusion and independently extracted data and assessed trial quality; any differences were resolved by reaching consensus. Authors of trials were contacted for further information as necessary. MAIN RESULTS: Thirty-one trials with 2464 randomised participants have been included in the review. Most included trials had poor study quality. Mortality data were combined for meta-analysis from twenty-two trials (1755 participants). The Relative Risk (RR) indicated a lower mortality in the supplemented group compared with the control group (0.67; 95% confidence interval (CI) 0.52 to 0.87). The risk of complications (total complications if available, otherwise for example the number of infections by the end of follow-up) from nine trials (608 participants) showed no significant difference (RR 0.93, 95% CI 0.77 to 1.13). We were unable to combine trials for meta-analyses of functional outcome, for example grip strength, walking distance and Barthel Index, however there was little evidence of benefit to functional outcomes from individual studies. Data describing length of stay were available from seven trials (658 participants). There was some indication that mean length of stay was shorter for the supplemented groups (-3.4 days, 95% CI -6.12 to -0.69). REVIEWER'S CONCLUSIONS: Supplementation appears to produce a small but consistent weight gain. There was a statistically significant beneficial effect on mortality and a shorter length of hospital stay. Additional data from large-scale multi-centre trials are still required to provide clear evidence of benefit from protein and energy supplements on mortality and length of hospital stay. Too few data were reported and the time scale of most studies was too short to have a realistic chance of detecting differences in morbidity, functional status and quality of life. Furthermore, most trials do not address the organisational and practical challenges faced by practitioners trying to meet the individual needs and preferences of those at risk from malnutrition.

Aged↗

An assessment of the release of inorganic cyanide from the fragrance materials benzyl cyanide, geranyl nitrile and citronellyl nitrile applied dermally to the rat.

Organonitriles are widely used as components of fragrances that are incorporated into consumer products, many of which are for human topical use. Some organontriles are readily broken down metabolically to potentially toxic inorganic cyanide. Studies were therefore undertaken to assess whether this occurs with three representative fragrance nitriles, namely, benzyl cyanide, geranyl nitrile and citronellyl nitrile when applied dermally to the rat. The nitriles (benzyl cyanide, 150 mg/kg; geranyl and citronellyl nitriles, 400 mg/kg) were applied to the shaved backs of rats and maintained under occlusion for 24 h. Urine samples were collected for 0-24 h, 24-48 h and 48-72 h from the time of first application. These samples were analysed for thiocyanate, a biomarker for cyanide formation in vivo, as described previously (Potter, J., Smith, R.L., Api, A.M., 2000. Urinary thiocyanate levels as a biomarker for the generation of inorganic cyanide from benzyl cyanide in the rat. Food and Chemical Toxicology 39, 141-146). In the case of benzyl cyanide, there was a marked increase in urinary thiocyanate levels attributable to the release of cyanide in vivo. The amount of thiocyanate recovered was equivalent to 37% of the dose for males and 32% for females. For geranyl nitrile there was no significant increase in urinary thiocyanate excretion and there was only a marginal increase in the case of citronellyl nitrile that was equivalent to 0.40% of the applied dose for males and 0.29% for females.

Acetonitriles↗

Urinary thiocyanate levels as a biomarker for the generation of inorganic cyanide from benzyl cyanide in the rat.

A colorimetric procedure was developed and validated for the determination of thiocyanate in rat urine over the concentration range of 7-7000 microg/ml. It was applied to the determination of thiocyanate following its oral administration to male and female rats. The mean percentage urinary recoveries of sodium thiocyanate given by oral gavage at 10 and 100 mg/kg were 60 and 39%, respectively, for male rats and 89 and 73% for females over a period of 3 days. Most of the elimination occurred in the 0-48-h period post-dosing but significant amounts were still being excreted in the 48-72-h period. It was concluded from these results that the recoveries of urinary thiocyanate were such that this anion was suitable for use as a biomarker for the release of cyanide from organonitriles such as benzyl cyanide. Benzyl cyanide (150 mg/kg) administered orally to rats led to markedly increased urinary thiocyanate levels; for male rats this was equivalent to 54% of the dose and for females this was 65% over a period of 3 days. When adjusted for incomplete recoveries of the marker, thiocyanate, these values equated to 61 and 89%, respectively. It was concluded that this validated assay could be used to assess cyanide release from topically applied fragrance organonitriles (Potter, J., Smith, R.L., Api, A.M., 2000. An assessment of the release of inorganic cyanide from the fragrance materials, benzyl cyanide, geranyl nitrile and citronellyl nitrile applied dermally to the rat. Food and Chemical Toxicology 39, 147-151).

Acetonitriles↗

WSX-1 is required for the initiation of Th1 responses and resistance to L. major infection.

WSX-1 is a class I cytokine receptor with homology to the IL-12 receptors. The physiological role of WSX-1, which is expressed mainly in T cells, was investigated in gene-targeted WSX-1-deficient mice. IFN-gamma production was reduced in isolated WSX-1(-/-) T cells subjected to primary stimulation in vitro to induce Th1 differentiation but was normal in fully differentiated and activated WSX-1(-/-) Th1 cells that had received secondary stimulation. WSX-1(-/-) mice were remarkably susceptible to Leishmania major infection, showing impaired IFN-gamma production early in the infection. However, IFN-gamma production during the later phases of the infection was not impaired in the knockout. WSX-1(-/-) mice also showed poorly differentiated granulomas with dispersed accumulations of mononuclear cells when infected with bacillus Calmette-Guerin (BCG). Thus, WSX-1 is essential for the initial mounting of Th1 responses but dispensable for their maintenance.

Animals↗

Measuring the quality of urinary continence care in long-term care facilities: an analysis of outcome indicators.

BACKGROUND: the National Centre for Health Outcomes Development has produced outcome indicators for the assessment of quality of care in the management of urinary incontinence. Three measures relate to the management of older people in long-term care: the prevalence of incontinence, the use of indwelling catheters and clinical assessment rates. OBJECTIVE: to evaluate the recommended outcome measures in clinical practice. METHOD: participating centres included residential homes, nursing homes and long-stay wards. We sent a structured questionnaire to each centre for qualitative assessment of the acceptability of the outcome indicators. We analysed data collected by nurses and other staff who used the urinary incontinence section of the Royal College of Physicians Continuous Assessment Review and Evaluation scheme audit tool for long-term care. RESULTS: there were 1125 residents in 17 residential homes, 14 nursing homes and five long-stay wards. The overall prevalence of urinary incontinence was 34% in residential homes (range 2-86%), 70% in nursing homes (38-100%) and 71% in long-stay wards (4-97%). Catheterization rates were 5% in residential homes (0-20%), 10% in nursing homes (0-44%) and 6% in long-stay wards (0-20%). Rates of full clinical assessment were 48, 24 and 36% respectively. CONCLUSION: there is great variability in these outcome measures within and between settings. Interpretation of outcome results requires more precise details on case-mix and the definition of outcome measures. Individual units found the audit tool helpful, but we advise caution with interpretation of outcomes between units.

Aged↗

Hypertension in the Very Elderly Trial (HYVET): protocol for the main trial.

A number of trials and meta-analyses have demonstrated clear benefits of blood pressure (BP) reduction in patients aged <80 years with regard to the reduction in stroke and cardiovascular events. However, a variety of studies have suggested that the positive relationship between BP and cardiovascular mortality is weakened or indeed reversed in the very elderly. Most intervention trials to date have either excluded or not recruited sufficient patients aged > or =80 years to determine whether there is a significant benefit from treatment in this age group. A meta-analysis of intervention trials that recruited patients aged > or =80 years has suggested a benefit in terms of stroke reduction but has also raised the possibility of an increase in total mortality. The benefit to risk ratio therefore needs to be clearly established before recommendations can be made for treating very elderly patients with hypertension. The Hypertension in the Very Elderly Trial (HYVET) pilot recruited 1283 patients aged > or =80 years and showed the feasibility of performing such a trial in this age group. It was a Prospective Randomised Open Blinded End-Points (PROBE) design but the main trial has additional pharmaceutical sponsorship to run a double-blind trial. Therefore, the main trial is a randomised, double-blind, placebo-controlled trial designed to assess the benefits of treating very elderly patients with hypertension. It compares placebo with a low dose diuretic (indapamide sustained release 1.5mg daily) and additional ACE inhibitor (perindopril) therapy if required. As in the pilot trial, the primary end-point is stroke events (fatal and non-fatal) and the trial is designed to determine whether or not a 35% difference occurs between placebo and active treatment. The main objective will be achieved with 90% power at the 1% level of significance. Secondary outcome measures will include total mortality, cardiovascular mortality, cardiac mortality, stroke mortality and skeletal fracture. 2100 patients aged > or =80 years are to be recruited and followed up for an average of 5 years. Entry BP criteria after 2 months of a single-blind placebo run-in period are a sustained sitting systolic BP (SBP) of 160 to 199mm Hg and a diastolic BP of 90 to 109mm Hg. The standing SBP must be >140mm Hg. The trial will be carried out in accordance with the principles of Good Clinical Practice. We describe in detail the protocol for the main trial and discuss the reasons for the changes from the pilot, the use of the drug regimen, and the BP criteria to be used in the trial.

Age Factors↗