Are the UK systems of innovation and evaluation of medical devices compatible? The role of NICE's Medical Technologies Evaluation Programme (MTEP).

The economic evaluation of medical products and services is increasingly prioritised by healthcare decision makers and plays a key role in informing funding allocation decisions. It is well known that there are a number of methodological difficulties in the health technology assessment of medical devices, particularly in the provision of efficacy evidence. By contrasting devices with pharmaceuticals, the way in which the differing systems of innovation mould the UK's industry landscape is described and substantiated with market statistics. In recognition of the challenges faced by industry, as well as the growing need for cost-effective allocation of National Health Service (NHS) resources, the National Institute for Health and Care Excellence (NICE) led the development of the Medical Technologies Evaluation Programme (MTEP), which launched in 2009/2010. The review of the UK's medical devices market supports the programme's three principal aims: to simplify access to evaluation, speed up the process, and increase evaluative capacity for devices within NICE. However, an analysis of the output of MTEP's first 3 years suggests that it has some way to go to meet each of these aims.

Cognitive dysfunction in older subjects with diabetes mellitus: impact on diabetes self-management and use of care services. All Wales Research into Elderly (AWARE) Study.

OBJECTIVE: To determine whether cognitive impairment is associated with changes in self-care behaviour and use of health and social services in older subjects with diabetes mellitus. RESEARCH DESIGN AND METHODS: This was a community based, case-control study of subjects registered with general practices participating in the All Wales Research into Elderly (AWARE) Diabetes Study. The 396 patients aged 65 years or older with known diabetes mellitus were compared with 393 age- and sex-matched, non-diabetic controls. Adjusted odds ratio estimates of normal performance on Mini-Mental State Examination (MMSE) and Clock Drawing Test (numbers and hands) were determined. Information on self-care behaviours and use of services was obtained. RESULTS: A total of 283 (71%) diabetic subjects scored 24 or more on MMSE, compared with 323 (88%) of controls (OR 0.54, P<0.0005). The mean (S.D.) scores were 24.5 (5.1) and 25.7 (4.3), respectively (difference between means 1.22; 95% CI 0.56, 1.88; P<0. 001). Clock testing demonstrated that 257 (65%) and 286 (72%) diabetic subjects correctly placed the numbers and hands, respectively, compared with 299 (76%) and 329 (84%) of controls (OR 0.59, P<0.001 and P<0.52, P<0.0005, respectively). Both test scores declined with increasing age, earlier school leaving age and deteriorating visual acuity. Of other variables examined, only need for oral hypoglycaemic drugs or insulin, history of stroke, dementia or Parkinson's disease and symptoms of autonomic neuropathy significantly impaired one or more cognitive test scores. The odds ratios (95% CI) for normal cognitive test results in subjects with diabetes after adjusting for all significant variables was 0.74 (0. 56, 0.97), P=0.029 for MMSE scores and 0.63 (0.44, 0.93), P=0.019, and 0.58 (0.38, 0.89), P=0.013, for the numbers and hands parts of the clock test, respectively. In comparison with diabetic subjects with no evidence of cognitive impairment, diabetic subjects with an MMSE score <23 were significantly less likely to be involved in diabetes self-care (P<0.001) and diabetes monitoring (P<0.001). A low MMSE score was also significantly associated with higher hospitalisation in the previous year (P=0.001), reduced ADL (activities of daily living) ability (P<0.001) and increased need for assistance in personal care (P=0.001). CONCLUSIONS: Elderly subjects with predominantly Type 2 diabetes mellitus display significant excess of cognitive dysfunction, associated with poorer ability in diabetes self-care and greater dependency. Routine screening of cognition in older subjects with diabetes is recommended.

Older adults, diabetes mellitus and visual acuity: a community-based case-control study.

MAIN OBJECTIVES: to screen for impaired distance visual acuity in older adults living at home, both with and without diabetes mellitus to determine whether diabetes increases the likelihood of visual impairment and to identify associated factors. DESIGN: case-control study. SETTINGS: three districts of Wales: North Clwyd, Powys and South Glamorgan, with assessments in subjects' homes. SUBJECTS: 385 with diabetes mellitus and 385 age- and sex-matched controls. MAIN OUTCOME MEASURES: visual acuity measures, short form (SF)-36 quality of life scores RESULTS: we observed impairment of visual acuity in 40% of those with diabetes mellitus and 31% of controls. Diabetes was associated with an increased risk of visual impairment [odds ratio 1.50 (95% confidence interval 1.09-2.05), P = 0.013]. The pinhole test identified uncorrected refractive error in 11% of the 63 patients with diabetes and 12% of the 49 controls who wore glasses, and in 51% of the 91 patients and 84% of the 69 controls who did not wear glasses (P < 0.001). Increasing age (P < 0.001) and female sex (P = 0.014) were significantly associated with visual impairment in both groups, whilst history of foot ulceration (P = 0.001), duration of diabetes (P = 0.018) and treatment with insulin (P < 0.001) were significantly associated with visual impairment in subjects with diabetes. We observed a significant association between impaired visual acuity and five domains of the SF-36 (physical and social functioning, mental health, vitality, and health perceptions; P < 0.01 in each case). CONCLUSION: older adults living at home have a high prevalence of uncorrected visual impairment. Diabetes mellitus is associated with significantly increased risk of visual loss. This impairment is associated with detriments in health-related quality of life. We recommend earlier use of optometry services and assessment of visual acuity by clinicians.

Low plasma ascorbate levels in patients with type 2 diabetes mellitus consuming adequate dietary vitamin C.

Low ascorbate concentrations in diabetes may be secondary to inadequate dietary vitamin C intake or may relate to the varied metabolic roles of the vitamin. To determine whether inadequate dietary intake is a factor we calculated daily vitamin C intakes using both a vitamin C questionnaire and a 4-day food diary in a group of 30 patients with Type 2 diabetes (mean age 68.8 +/- 6.9 yr, 17M/13F) and in 30 community controls (mean age 68.0 +/- 5.5 yr, 12M/18F)). Measures of plasma glucose, serum fructosamine, and plasma ascorbic and dehydroascorbic acid were obtained from 20 subjects in each group. There was no significant difference in daily vitamin C intake between the two groups using both methods: food diary, 61.4 +/- 28.3 (patients) vs 69.5 +/- 33.4 (controls) mg; questionnaire, 54.0 +/- 28.9 (patients) vs 65.0 +/- 30.9 (controls) mg. Vitamin C intake derived from both methods was significantly correlated (p < 0.001). Plasma ascorbate (30.4 +/- 19.1 mumol l-1) and dehydroascorbate (27.6 +/- 6.4 mumol l-1) levels were significantly lower in patients vs in controls (68.8 +/- 36.0 and 31.8 +/- 4.8 mumol l-1, respectively), p < 0.0001 and p < 0.01. Plasma ascorbate levels were significantly correlated with vitamin C intake derived from the food diary (p < 0.01) and questionnaire (p < 0.01) methods in the diabetic group only. Low ascorbate levels in diabetes appears to be a consequence of the disease itself and not due to inadequate dietary intake of vitamin C. A short vitamin C questionnaire is a convenient and reliable estimate of vitamin C intake.(ABSTRACT TRUNCATED AT 250 WORDS)

A double-blind, placebo-controlled parallel trial of vitamin C treatment in elderly patients with hypertension.

We have investigated the effect on blood pressure of treatment with vitamin C (an antioxidant and free radical scavenger) in patients with both systolic and essential hypertension. Following a 2-week run-in phase, two age- and sex-matched groups of untreated hypertensive subjects were randomised in a double-blind study to receive 6 weeks' oral treatment with either vitamin C, 250 mg twice daily (n = 22; 8M/14F, mean age 73.7 +/- 4.9 years) or placebo, one capsule twice daily (n = 26; 10M/16F, mean age 73.8 +/- 5.3 years). Blood pressure was measured in the sitting position using a random zero sphygmomanometer on three occasions during the run-in phase, and again at 2, 4 and 6 weeks after commencing treatment. Venous blood samples for measurement of plasma ascorbic acid (AA) and lipid peroxides (LP) were measured in all subjects at baseline and at 4 and 6 weeks after the start of vitamin C or placebo treatment. During the study period, significant falls in both systolic (vitamin C group, mean change -10.3 (95% CI 0.7-20.0) mm Hg, p = 0.05) and diastolic (vitamin C group, mean change -5.9 (95% CI 0.2-11.5) mm Hg, p = 0.03; placebo group, mean change -4.7 (95% CI 0.3-9.1) mm Hg, p = 0.05) blood pressure occurred. However, no statistical difference between the effects of either treatment on blood pressure was observed. At baseline, AA concentrations were lower in the vitamin C-treated group compared with the placebo group (44.6 +/- 2.4 vs. 57.7 +/- 4.2 mumol/l, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

The IC50: an exactly defined measure of antibiotic sensitivity.

The concentration of gentamicin that inhibits the growth of half of an inoculum of Pseudomonas aeruginosa (IC50) was estimated by doing viable bacterial counts with varying concentrations of gentamicin and fitting a probit inhibition curve to the results. This is a more precisely defined measure than the MIC and its standard error is readily calculable.

Modulators of free radical activity in diabetes mellitus: role of ascorbic acid.

Free radical mechanisms are increasingly being implicated in the pathogenesis of tissue damage in diabetes. Various sources of free radicals may modulate oxidative stress in diabetes, including non-enzymatic glycosylation of proteins and monosaccharide autooxidation, polyol pathway activity, indirect production of free radicals through cell damage from other causes, and reduced antioxidant reserve. Ascorbic acid, which may be a principal modulator of free radical activity in diabetes, is shown to be consumed, presumably through free radical scavenging, thus preserving levels of other antioxidants such as glutathione.

An investigation of the relationship between free radical activity and vitamin C metabolism in elderly diabetic subjects with retinopathy.

Abnormalities of both free radical activity and ascorbic acid metabolism have been documented in diabetes, but their biological basis is unclear and their relationship unstudied in any detail. This study was designed to compare changes in antioxidant status and free radical reactions in a group of elderly diabetic patients (with and without retinopathy) with those in a group of age-matched control subjects. No significant differences in thiobarbituric acid (TBA) reactivity, red cell glutathione (GSH) concentrations or diene conjugates (DC) between patients and controls were seen despite significant depletion of ascorbic acid in patients with diabetes, especially in those with retinopathy. The results emphasise the present-day difficulties of measuring free radical activity and demonstrate a marked abnormality in ascorbic acid metabolism in diabetes.

Disturbed handling of ascorbic acid in diabetic patients with and without microangiopathy during high dose ascorbate supplementation.

Abnormalities of ascorbic acid metabolism have been reported in experimentally-induced diabetes and in diabetic patients. Ascorbate is a powerful antioxidant, a cofactor in collagen biosynthesis, and affects platelet activation, prostaglandin synthesis and the polyol pathway. This suggests a possible close interrelationship between ascorbic acid metabolism and pathways known to be influenced by diabetes. We determined serum ascorbic acid and its metabolite, dehydroascorbic acid, as indices of antioxidant status, and the ratio, dehydroascorbate/ascorbate, as an index of oxidative stress, in 20 matched diabetic patients with and 20 without microangiopathy and in 22 age-matched control subjects. Each study subject then took ascorbic acid, 1 g daily orally, for six weeks with repeat measurements taken at three and six weeks. At baseline, patients with microangiopathy had lower ascorbic acid concentrations than those without microangiopathy and control subjects (42.1 +/- 19.3 vs 55.6 +/- 20.0, p less than 0.01, vs 82.9 +/- 30.9 mumol/l, p less than 0.001) and elevated dehydroascorbate/ascorbate ratios (0.87 +/- 0.46 vs 0.61 +/- 0.26, p less than 0.01, vs 0.38 +/- 0.14, p less than 0.001). At three weeks, ascorbate concentrations rose in all groups (p less than 0.0001) and was maintained in control subjects (151.5 +/- 56.3 mumol/l), but fell in both diabetic groups by six weeks (p less than 0.01). Dehydroascorbate/ascorbate ratios fell in all groups at three weeks (p less than 0.0001) but rose again in the diabetic groups by six weeks (p less than 0.001) and was unchanged in the control subjects. Dehydroascorbate concentrations rose significantly from baseline in all groups by six weeks of ascorbic acid supplementation (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

The value of the Claybury Selection Battery in predicting benefit from group psychotherapy.

Before receiving psychodynamic group psychotherapy at the Uffculme Clinic four groups of out-patients were assessed on the Claybury Selection Battery and the SCL 90, and therapists were asked to predict their progress. Outcome was assessed at about three months and one year by patients' self-reports of symptom change on the SCL 90 and therapists' ratings of progress. Only one of the three Claybury questionnaires, the TEQ, which measures attitudes to treatment, was significantly correlated with outcome, along with therapists' predictions. This result is different to that of a previous study which also found that outcome correlated with direction of interest (DIQ) and conservatism (C). The C and DIQ scales may provide useful predictive information only in a small proportion of cases.

Gentamicin and low dose piperacillin in febrile neutropenic patients.

One hundred and twenty-seven febrile neutropenic patients were randomized to receive empirical antibiotic therapy with intravenous gentamicin and 12 g/day or 8 g/day piperacillin. Despite a high incidence of Hickman catheter infections by antibiotic-resistant bacteria, there was an overall response in 56% of patients and no difference in the numbers responding to each antibiotic regimen. In addition, the duration of fever was not significantly different in the two groups of patients. The majority of the unresponsive patients responded to the addition of further antibiotics and there were only two infection related deaths. The results suggest that high dose antibiotics are not essential for the initial empirical therapy in febrile neutropenic patients.

A simple method for assessment of glomerular size and its use in the study of kidneys in acromegaly and compensatory renal enlargement.

As measurement of absolute glomerular size is difficult we developed a method of assessing glomerular size that was simple and practical and could be used to compare the kidneys in different groups of patients. Using a semi-automatic image analyser, the cross-sectional area of 100 randomly-selected glomeruli, outlined by Bowman's capsule, was measured on sections of kidneys taken at necropsy. The mean of the logarithms of the largest 25 areas was calculated. The method was applied to compare control kidneys (53) with the kidneys in acromegalics (20), in patients with one kidney (10) and in patients with asymmetrical kidneys (12). Kidneys were heavier in the three test groups than in controls. Glomerular sizes were similar in controls and in acromegalics but were larger in single and disparate kidneys. There was a relationship between glomerular size and kidney weight within the control group and across the four groups taken together. This only partly accounted for the observed differences in glomerular size between the groups. Histological comparison of the acromegalic and single kidneys showed more global glomerulosclerosis in single kidneys and also segmental lesions, mainly at the glomerular hilum, only in the single kidneys. These findings show that renal enlargement occurs in acromegaly and in single and disparate kidneys but is accompanied by markedly different glomerular features. This implies different mechanisms for the renal enlargement. The method of assessing glomerular size is useful in the study of these and other conditions affecting the kidney.

Effect of polymerization tendency on haematological, rheological and clinical parameters in sickle cell anaemia.

The polymerization tendency of sickle haemoglobin was estimated as a function of oxygen saturation in 30 patients with homozygous sickle cell anaemia. The deformability of their erythrocytes was also measured, by initial-flow-rate filtration at 37 degrees C through pores of 5 microns diameter, and clinical severity was assessed using a visual analogue scale. By means of partial correlation analysis, it was found that correlations between haematological, rheological, and clinical parameters in sickle cell anaemia could be explained on the basis of an association of each variable with polymerization tendency. Patients with the greatest tendency to form polymer had the least deformable erythrocytes and perceived their disease to be more severe as judged by the visual analogue scale. Polymer formation also appeared to be a determinant of the number of dense cells which, in turn, determine haemolytic rate and erythrocyte deformability.

Vascular innervation in human skeletal muscle with and without neuromuscular disease. A quantitative ultrastructural study with references to the effects of age and different blood pressure.

A quantitative ultrastructural study has been made of the innervation of 461 arterioles in 114 skeletal muscle biopsies of patients with or without neuromuscular disease excluding diabetes and autonomic neuropathy. In 18 controls the number of nerves and Schwann cells around each vessel was related to the size of the vessel, whether the vessel was within a muscle fascicle or between muscle fascicles. The innervation of arterioles increased with increased diastolic blood pressure. There was no statistically significant change in innervation with increased systolic blood pressure or with age, from 4 to 85 years. In 96 cases of neuromuscular disease and especially in motor neurone disease, axonal varicosities in cross section tended to be larger, more often contained no vesicles or only a few and had altered satellite cell cover depending on the location of the arteriole. Whilst the numerical density of Schwann cells did not change with disease, fewer varicosities were identified within Schwann cells in motor neurone disease, metabolic myopathy and neuropathy and myopathy due to toxins or vascular disease. Preterminal axons in nerve fascicles adjacent to arterioles were lost in polymyositis and muscle disease due to toxins or vascular disease. In polymyositis, metabolic myopathy and motor neurone disease there was some evidence of compensatory nerve sprouting, either in the nerve fascicles or in the adventitia of the arterioles. These structural changes may be related to the changes in blood flow or vascular reactivity described by others in motor neurone disease, polymyositis and metabolic myopathy. It is concluded that the ultrastructure of the vascular innervation of human skeletal muscle is similar to that in other mammals and is changed more with increased diastolic blood pressure and neuromuscular disease than with age.