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I Stratton

Publications and source records attributed to I Stratton.

At least 19 recordsLinked to original sources
PubMed2001

Cost-effectiveness analysis of intensive blood-glucose control with metformin in overweight patients with type II diabetes (UKPDS No. 51).

AIMS/HYPOTHESIS: To estimate the economic efficiency of intensive blood-glucose control with metformin compared with conventional therapy primarily with diet in overweight patients with Type II (non-insulin-dependent) diabetes mellitus. METHODS: Cost-effectiveness analysis based on patient level data from a randomised clinical controlled trial involving 753 overweight (> 120% ideal body weight) patients with newly diagnosed Type II diabetes conducted in 15 hospital-based clinics in England, Scotland and Northern Ireland as part of the UK Prospective Diabetes Study. Subjects were allocated at random to an intensive blood-glucose control policy with metformin (n = 342) or a conventional policy primarily with diet (n = 411). The analysis was based on the cost of health care resources associated with metformin and conventional therapy and the estimated effectiveness in terms of life expectancy gained from within-trial effects. RESULTS: Intensive blood-glucose control with metformin produced a net saving of 258 Pounds per patient (1997 United Kingdom prices) over the trial period (median duration of 10.7 years) due to lower complication costs, and increased life expectancy by 0.4 years (costs and benefits discounted at 6%). CONCLUSIONS/INTERPRETATION: As metformin is both cost-saving in the United Kingdom and extends life expectancy when used as first line pharmacological therapy in overweight Type II diabetic patients, its use should be attractive to clinicians and health care managers alike.

Adult↗
PubMed2001

An economic evaluation of atenolol vs. captopril in patients with Type 2 diabetes (UKPDS 54).

AIMS: To compare the net cost of a tight blood pressure control policy with an angiotensin converting enzyme inhibitor (captopril) or beta blocker (atenolol) in patients with Type 2 diabetes. DESIGN: A cost-effectiveness analysis based on outcomes and resources used in a randomized controlled trial and assumptions regarding the use of these therapies in a general practice setting. SETTING: Twenty United Kingdom Prospective Diabetes Study Hospital-based clinics in England, Scotland and Northern Ireland. SUBJECTS: Hypertensive patients (n = 758) with Type 2 diabetes (mean age 56 years, mean blood pressure 159/94 mmHg), 400 of whom were allocated to the angiotensin converting enzyme inhibitor captopril and 358 to the beta blocker atenolol. MAIN OUTCOME MEASURES: Life expectancy and mean cost per patient. RESULTS: There was no statistically significant difference in life expectancy between groups. The cost per patient over the trial period was 6485 UK pounds in the captopril group, compared with 5550 UK pounds in the atenolol group, an average cost difference of 935 UK pounds (95% confidence interval 188 UK pounds, 1682 UK pounds). This 14% reduction arose partly because of lower drug prices, and also because of significantly fewer and shorter hospitalizations in the atenolol group, and despite higher antidiabetic drug costs in the atenolol group. CONCLUSIONS: Treatment of hypertensive patients with Type 2 diabetes using atenolol or captopril was equally effective. However, total costs were significantly lower in the atenolol group. Diabet. Med. 18, 438-444 (2001)

Adrenergic beta-Antagonists↗
PubMed2001

Underestimation of the importance of homocysteine as a risk factor for cardiovascular disease in epidemiological studies.

BACKGROUND: In epidemiological studies, within-person variability in plasma total homocysteine (tHcy) measurements may dilute the association of 'usual' levels of tHcy with risk of cardiovascular disease, referred to as 'regression dilution'. The aim of this report was to estimate the magnitude of regression dilution after varying intervals of follow-up. METHODS: Regression dilution ratios (RDR) for tHcy were calculated using replicate tHcy measurements obtained after 3, 6 and 8 years from the Rotterdam, Hordaland and Framingham studies, respectively, and after 3, 6, 9 and 12 years from the United Kingdom Prospective Study of type 2 Diabetes Mellitus (UKPDS). RESULTS: The RDR for tHcy decreased with increasing interval in the three population-based studies and in the UKPDS. Moreover, the rate of decline of the RDR in the population-based studies was similar to that obtained in the UKPDS. Using linear regression analysis for the population-based studies, these results suggest an RDR of 0.83 at 2 years, 0.71 at 6 years and 0.53 at 12 years. CONCLUSIONS: These results have important implications for the interpretation of prospective studies of tHcy and cardiovascular disease. Failure to correct for increasing regression dilution using lower RDRs for longer follow-up may underestimate the relative risks of cardiovascular disease associated with tHcy by about one-fifth after 2 years and one-half after 10 years.

Aged↗
PubMed2000

Cost effectiveness of an intensive blood glucose control policy in patients with type 2 diabetes: economic analysis alongside randomised controlled trial (UKPDS 41). United Kingdom Prospective Diabetes Study Group.

OBJECTIVE: To estimate the cost effectiveness of conventional versus intensive blood glucose control in patients with type 2 diabetes. DESIGN: Incremental cost effectiveness analysis alongside randomised controlled trial. SETTING: 23 UK hospital clinic based study centres. PARTICIPANTS: 3867 patients with newly diagnosed type 2 diabetes (mean age 53 years). INTERVENTIONS: Conventional (primarily diet) glucose control policy versus intensive control policy with a sulphonylurea or insulin. MAIN OUTCOME MEASURES: Incremental cost per event-free year gained within the trial period. RESULTS: Intensive glucose control increased trial treatment costs by pound 695 (95% confidence interval pound 555 to pound 836) per patient but reduced the cost of complications by pound 957 (pound 233 to pound 1681) compared with conventional management. If standard practice visit patterns were assumed rather than trial conditions, the incremental cost of intensive management was pound 478 (-pound 275 to pound 1232) per patient. The within trial event-free time gained in the intensive group was 0.60 (0.12 to 1.10) years and the lifetime gain 1.14 (0.69 to 1.61) years. The incremental cost per event-free year gained was pound 1166 (costs and effects discounted at 6% a year) and pound 563 (costs discounted at 6% a year and effects not discounted). CONCLUSIONS: Intensive blood glucose control in patients with type 2 diabetes significantly increased treatment costs but substantially reduced the cost of complications and increased the time free of complications.

Adult↗
PubMed1999

Genetic heterogeneity of autoimmune diabetes: age of presentation in adults is influenced by HLA DRB1 and DQB1 genotypes (UKPDS 43). UK Prospective Diabetes Study (UKPDS) Group.

AIMS/HYPOTHESIS: Juvenile-onset, insulin-dependent diabetes is associated with islet cell antibodies and with specific "high-risk" HLA-DRB1 and HLA-DQB1 genotypes. Patients with Type II (non-insulin-dependent) diabetes mellitus can have islet-related antibodies, but the genotypic associations at different ages of onset have not been evaluated. Our aim was to determine (i) the prevalence of DRB1 and DQB1 genotypes in patients at diagnosis of Type II diabetes at different ages from 25 to 65 years compared with the general population, and (ii) whether the presence of islet cell antibodies (ICA) or glutamic acid decarboxylase antibodies (GADA) or both by age is associated with different DRB1 and DQB1 genotypes. METHODS: The antibodies to islet cells and those to glutamic acid decarboxylase were measured in 1712 white Caucasian diabetic subjects at diagnosis of diabetes and they were genotyped for HLA DRB1*03 and DRB1*04 and the high-risk DRB1*04-DQB1* 0302 haplotype. To assess over-representation of high-risk alleles for Type I (insulin-dependent) diabetes mellitus, the prevalence of high-risk alleles in diabetic patients was expressed relative to the prevalence of low-risk alleles, non-DR3/non-DR4, that provided a reference denominator in both the diabetic patients and in 200 non-diabetic control subjects. The prevalence of ICA or GADA or both in patients with different HLA genotypes was assessed in those diagnosed in four age groups, 25-34 years, 35-44 years, 45-54 years and 55-65 years. RESULTS: In Type II diabetic patients presenting at ages 25-34, 35-44 and 45-54 years, there was an increased prevalence of DR3/DR4 compared with the general population with approximately 6.5-fold, 2.9-fold, 2.1-fold over-representation, respectively (p < 0.0001, < 0.01, < 0.05) but this was not found in those aged 55-65 years old. In the group aged 25-34 years, 32 % of patients with ICA or GADA or both had DRB1*03/DRB1*04-DQB1*0302 compared with 10% in those aged 55-65 years and expected 3% prevalence. Conversely, only 14% of those aged 25-34 years with antibodies had non-DR3/non-DR4, compared with 35 % in those aged 55-65 years. There was thus pronounced age heterogeneity in DRB1 and DQB1 predisposition to Type II diabetes. The antibodies displaced DRB1 or DQB1 genotypes in the multivariate model for requiring insulin therapy by 6 years of follow-up. CONCLUSION/HYPOTHESIS: The age of presentation of Type I diabetes in adulthood was in part dependent on the DRB1/DQB1 genotype. Islet cell antibodies and glutamic acid decarboxylase antibodies were strongly associated with DRB1*03/DRB1*04-DQB1*0302 in early adulthood but showed little relation with specific HLA genotypes after the age of 55 years.

Adult↗
PubMed1999

Microalbuminuria prevalence varies with age, sex, and puberty in children with type 1 diabetes followed from diagnosis in a longitudinal study. Oxford Regional Prospective Study Group.

OBJECTIVE: The predictive value of microalbuminuria (MA) in children with type 1 diabetes has not been defined. We describe the natural history of MA in a large cohort of children recruited at diagnosis of type 1 diabetes. RESEARCH DESIGN AND METHODS: Between 1985 and 1996, 514 children (279 male) who developed type 1 diabetes before the age of 16 years (91% of those eligible from a region where ascertainment of new cases is 95%) were recruited for a longitudinal study with central annual assessment of HbAlc and albumin excretion (three urine samples). Dropout rates have been < 1% per year, and 287 children have been followed for > 4.5 years. RESULTS: MA (defined as albumin-to-creatinine ratio > or = 3.5 and > or = 4.0 mg/mmol in boys and girls, respectively) developed in 63 (12.8%) and was persistent in 22 (4.8%) of the subjects. The cumulative probability (based on the Kaplan-Meier method) for developing MA was 40% after 11 years. HbAlc was worse in those who developed MA than in others (mean difference +/- SEM: 1.1% +/- 0.2, P < 0.001). In subjects who had been 5-11 years of age when their diabetes was diagnosed, the appearance of MA was delayed until puberty, whereas of those whose age was < 5 years at diagnosis of diabetes, 5 of 11 (45%) developed MA before puberty. The adjusted proportional probability (Cox model) of MA was greater for female subjects (200%), after pubertal onset (310%), and with greater HbAlc (36% increase for every 1% increase in HbAlc). Despite earlier differences based on age at diagnosis of diabetes (< 5, 5-11, and > 11 years), the overall cumulative risks in these groups were similar (38 vs. 29 vs. 39%, respectively) after 10 years' duration of diabetes. CONCLUSIONS: Prepubertal duration of diabetes and prepubertal hyperglycemia contribute to the risk of postpubertal MA. The differences in rates of development of MA relating to HbAlc, sex, and age at diagnosis relative to puberty may have long-term consequences for the risk of subsequent nephropathy and for cardiovascular risk.

Adolescent↗
PubMed1997

UKPDS 25: autoantibodies to islet-cell cytoplasm and glutamic acid decarboxylase for prediction of insulin requirement in type 2 diabetes. UK Prospective Diabetes Study Group.

BACKGROUND: Autoantibodies to islet-cell cytoplasm (ICA) and glutamic acid decarboxylase (GADA) can occur in apparently typical, non-insulin dependent diabetes mellitus (type 2). We investigated whether the presence of either or both antibodies characterises a subtype of diabetes and provides better prediction of requirement for insulin therapy by 6 years' follow-up than clinical variables. METHODS: We measured ICA and GADA at diagnosis of diabetes in a representative population of 3672 white patients with type 2 diabetes, aged between 25 and 65 years. The phenotype was assessed by age of onset, body-mass index, percentage haemoglobin A1c (HbA1c), and islet beta-cell function. We investigated the need for insulin therapy among 1538 patients not assigned insulin and followed up for 6 years from diagnosis. FINDINGS: The proportion of patients with ICA and GADA decreased with increasing age at diagnosis (from 33 [21%] of 157 patients aged 25-34 [corrected] to 66 [4%] of 1769 aged 55-65 for ICA; from 53 [34%] to 122 [7%] for GADA). Among patients younger than 35 at diagnosis, those with ICA or GADA had lower body-mass index than those without (mean 24.9 [SD 6.0] vs 31.7 [7.3] kg/m2; p < 0.0001 and had higher percentage of HbA1c (9.7 vs 8.7%, p < 0.05). 94% of patients with ICA and 84% of those with GADA required insulin therapy by 6 years, compared with 14% of those without the antibodies (p < 0.0001). Among patients older than 55 at diagnosis, the difference between those with and without antibodies in body-mass index was smaller (27.2 [5.4] vs 28.6 [4.8] kg/m2, p < 0.001); 44% of those with ICA, 34% of those with GADA, and 5% with neither antibody required insulin therapy by 6 years (p < 0.0001). Among patients older than 45 years, body-mass index and HbA1c provided little predictive information for insulin requirement, whereas the positive predictive values of GADA (> or = 60 U/L) alone, or both GADA (> or = 20 U/L) and ICA (> 5 U/L), for insulin therapy were 52% and 68%. INTERPRETATION: Among young adults with type 2 diabetes, the phenotype of those with ICA or GADA antibodies was similar to that of classic juvenile-onset insulin-dependent diabetes, and either phenotype or antibodies predicted insulin requirement. In older adults, the phenotype was closer to that of patients without antibodies and only the presence of antibodies predicted an increased likelihood of insulin requirement.

Adult↗
PubMed1994

Chromosome 4q locus associated with insulin resistance in Pima Indians. Studies in three European NIDDM populations.

Markers on chromosome 4q have recently been shown to be associated with insulin resistance in Pima Indians, a population in which insulin resistance precedes and predicts the development of non-insulin-dependent diabetes mellitus (NIDDM). To examine whether genes in this region could play a major role in susceptibility to NIDDM in other populations, we have examined the allele frequencies of a trinucleotide repeat near the fatty acid-binding protein 2 (FABP2) gene on 4q28-31 in three European populations: Finnish, U.K. Caucasian, and Welsh. The U.K. NIDDM population was selected for insulin resistance by studying patients whose obesity-corrected fasting plasma insulin before treatment was above the 98th percentile. Seven alleles were detected. On cross-tabulation analysis, there were no significant associations between allele frequencies and glucose intolerance in any of the populations. Log-linear analysis of the results from all three populations suggested a moderately significant interaction of glucose tolerance status (normal versus diabetic) and the FABP2 allele (partial chi 2 = 24, df 6, P = 0.027). The parameter describing the interaction of allele A3 and glucose tolerance status was the only such parameter differing significantly from zero (z-score +2.003, P = 0.046). In both the Finnish and U.K. population, the A3 allele was found approximately twice as frequently in NIDDM than in control subjects (Finnish control subjects, impaired glucose tolerance, and NIDDM: 12.2, 22.4, and 26.6%, respectively; U.K. control subjects and NIDDM: 7.8 and 14.6%, respectively). In the Finnish populations, no associations were found between FABP2 alleles and plasma insulin levels or with homeostatic model assessment (HOMA) estimates of beta-cell function and insulin sensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Diabetes screening.

Explore the source record for details and available documents.

Diabetes Mellitus, Type 2↗
PubMed1992

Rate of change (modulation) of serum growth hormone concentrations is a more important factor in determining growth rate than duration of exposure.

OBJECTIVE: To determine whether duration of exposure to GH and/or rate of change of serum GH concentration are important factors in determining the growth rate of short children. DESIGN: An analysis of parameters of occupancy percentage and rate of change of serum GH concentration was performed as part of a prospective study investigating the relationship between growth and GH in childhood. PATIENTS: Sixty-four short prepubertal children (48 male, 16 female) aged between 4.7 and 11.9 years were studied. Thirty-one children were growing with a height velocity standard deviation score between 0 and -0.8 and were defined as short normal. Thirty-three children were growing with a height velocity standard deviation score less than -0.8 and were defined as short slowly growing. MEASUREMENTS: Twenty-four hour serum GH concentration profiles were constructed by withdrawing samples at 20-minute intervals. Analysis of occupancy percentage was performed on each data array by determining cumulative distributions and plotting these as linear probits against log serum GH concentration. Estimates of peak (OC95), intermediate (OC50) and trough (OC5) occupancies were calculated. A first-order derivative of the concentration-time data array was determined for each profile as a measure of rate changes. RESULTS: First-order derivative values were significantly greater in the short normal group than in the short slowly growing children (short normal median 1.41 mU/l/min; short slowly growing median 0.72 mU/l/min; P less than 0.001). OC95 values were significantly higher in the short normal group (median 19.31 mU/l) than the short slowly growing group (median 7.69 mU/l) (P less than 0.001). There was no difference in OC50 values. OC5 values were lower in short normal children (median 0.20 mU/l) than in the short slowly growing children (0.55 mU/l) (P less than 0.003). The most important factor in determining growth rate was the rate of change in serum GH concentration (FOD). Occupancy percentage played no part in the relationship. The regression equation was Height velocity SDS = 1.16 (In FOD) - 1.03; r = 0.75; P less than 0.001 CONCLUSIONS: These data suggest that the pattern of presentation of GH in the circulation is an important factor in determining target organ response. Although occupancy percentages at differing serum GH concentrations differ between short slowly growing and short normal children, it is the rate of change of the hormone in the circulation which appears to be the more important 'signal' in terms of modulating growth.

Child↗
PubMed1991

The physiological action of gliclazide: beta-cell function and insulin resistance.

There is continuing debate about the physiological mechanisms of the action of sulphonylureas in man. In those patients taking sulphonylureas insulin secretion can be demonstrated to be higher, but there are also data which have been interpreted as evidence that these drugs may cause an alteration in peripheral insulin sensitivity. The physiological effects of the sulphonylurea gliclazide in diabetic subjects has been examined using a variety of experimental protocols to address this question: an intravenous gliclazide infusion, experiments using glucose clamping, mathematical modelling of the insulin and glucose data from subjects on and off gliclazide therapy, and the infusion of amino acids and glucose separately or in combination. The data from all these analyses suggest that the primary effect of gliclazide is on the beta-cell and that any effects on the peripheral insulin sensitivity are either slight or secondary to the improvement of the secretory capacity of the pancreatic islets.

Amino Acids↗
PubMed1988

The influence of method of contraception and cigarette smoking on menstrual patterns.

Self-perceived menstrual patterns have been investigated in a sample of 2115 women aged 18-49 years using a postal questionnaire. Seven aspects of 'abnormal' menstruation were defined: prolonged periods, heavy periods, frequent periods, irregular periods, intermenstrual bleeding, painful periods and severe premenstrual syndrome. Women who used oral contraceptives were less likely than other women to report any of the seven menstrual abnormalities except for intermenstrual bleeding and severe premenstrual tension. Women who used an intrauterine contraceptive device (IUCD) reported prolonged, heavy, and frequent periods and intermenstrual bleeding more often than other women, but they did not report painful periods with undue frequency. Women who had had a tubal sterilization generally reported menstrual patterns similar to, or slightly less favourable than, women using no contraception or contraceptive methods other than the pill or the IUCD. There was a significant association between smoking habits and each of the abnormal menstrual patterns except for severe premenstrual tension. In every case, the effect of smoking was unfavourable and in almost every case, current smokers reported the worst experience, with ex-smokers occupying an intermediate position. We believe that these data are of considerable clinical significance and that they offer a basis for a conservative approach to managing menstrual disorders in some women.

Adult↗
PubMed1986

Mortality of nitrate fertiliser workers.

An epidemiological cohort study was conducted to investigate the mortality patterns among a group of workers engaged in the production of nitrate based fertilisers. This study was designed to test the hypothesis that individuals exposed to high concentrations of nitrates might be at increased risk of developing cancers, particularly gastric cancer. A total of 1327 male workers who had been employed in the production of fertilisers between 1946 and 1981 and who had been occupationally exposed to nitrates for at least one year were followed up until 1 March 1981. In total, 304 deaths were observed in this group and these were compared with expected numbers calculated from mortality rates in the northern region of England, where the factory was located. Analysis was also carried out separately for a subgroup of the cohort who had been heavily exposed to nitrates--that is, working in an environment likely to contain more than 10 mg nitrate/m3 for a year or longer. In neither the entire cohort nor the subgroup was any significant excess observed for all causes of mortality or for mortality from any of five broad categories of cause or from four specific types of cancer. A small excess of lung cancer was noted more than 20 years after first exposure in men heavily exposed for more than 10 years. That men were exposed to high concentrations of nitrate was confirmed by comparing concentrations of nitrates in the saliva of a sample of currently employed men with control men, employed at the same factory but not in fertiliser production. The men exposed to nitrate had substantially raised concentrations of nitrate in their saliva compared with both controls within the industry and with men in the general population and resident nearby. The results of this study therefore weight against the idea that exposure to nitrates in the environment leads to the formation in vivo of material amounts of carcinogens.

Aged↗
PubMed1985

Increasing use of private practice by patients in Oxford requiring common elective surgical operations.

A random sample of 6000 people from eight general practices in and around Oxford was studied to ascertain their surgical histories and method of care received. The proportion of operations that were performed privately had increased with time and had a steep gradient according to social class. Different procedures had different likelihoods of being performed privately, but the age and sex of the patient had a non-significant association with private surgery. Adjustment for possible confounding variables using logistic analysis indicated that in the 1980s elective surgery is five times more likely to be performed privately than it was at the institution of the National Health Service.

Adult↗
PubMed1984

Breast cancer: views of general practitioners on its detection and treatment.

A considerable proportion of women with breast cancer in this country present for treatment in late stages of the disease; Britain's primary health-care system means that in most cases the possible diagnosis of breast cancer is first made in general practice. This offers ample opportunity for early diagnosis and a better understanding about the way the general practitioners perceive the problems associated with the disease. With that specific aim, the present article reports on a survey conducted simultaneously in Oxford and in Edinburgh. Results show that general practitioners in the survey are deeply concerned about breast cancer and see a definite role for themselves in its early detection and long-term management. They also see a need for more health education that includes the encourgement of breast self-examination programmes. Most are in favour of open-access breast clinics for women and, in general, they feel positive about self-education programmes.

Adult↗
PubMed1983

A prospective study of urinary androgen levels and ovarian cancer.

The three major urinary androgen metabolites, dehydroepiandrosterone (DHEA), androsterone (ANDRO), and aetiocholanolone (AETIO) were measured in 1,484 volunteer women between 29 and 60 years of age on the island of Guernsey from 1962-1967. Twelve of these women subsequently developed ovarian cancer after a median interval of 130 months and a minimum interval of 19 months. All three androgen levels in these women were lower than those in controls matched for age and menopausal status. The results were most striking for DHEA, where half of the cases were below the 27th percentile of their matched controls (p = 0.007, two-sided). The results for ANDRO were of marginal significance (p = 0.06), and those for AETIO were not significant (p = 0.33).

Adult↗
PubMed1983

Group sequential clinical trials with triangular continuation regions.

In this paper a new class of group sequential procedures for clinical trials is introduced, and the use of these procedures is illustrated by reference to a recently completed comparative study. In a group sequential trial the decision to stop or to continue is made at regular intervals throughout the trial, but not as frequently as after every patient response. This more practical formulation retains most of the advantages of sequential analysis, particularly the economy in sample size. Comparisons are made with group sequential designs derived from the repeated significance test.

Anesthetics↗