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Biomedical subjects

Derek G Cook

Publications and source records attributed to Derek G Cook.

At least 19 recordsLinked to original sources
PubMed2007

Trends in potentially inappropriate prescribing amongst older UK primary care patients.

PURPOSE: To examine trends in UK primary care prescribing of medications potentially inappropriate for older people in the context of published international data. METHODS: Analysis of routinely collected anonymised computerised patient records in 131 UK general practices (approximately 162,000 registered patients annually aged >or=65 years) providing data to the DIN-LINK database between 1994 and 2003. In each year, we identified patients prescribed drugs classified by the 2003 Beers criteria as potentially inappropriate for older people. RESULTS: The level of potentially inappropriate prescribing remained steady over time: in 2003 32.2% of patients received any Beers drug, and 20.5% received a drug categorised as potentially "high risk"; percentages had been 32.9% and 21.4% respectively in 1994. In 2003, co-proxamol (93.7/1000 patients), benzodiazepines (52.4/1000 patients) and amitriptyline (45.4/1000, mainly at low doses) were the most frequently prescribed potentially inappropriate drugs. If co-proxamol (now being withdrawn) and low-dose amitriptyline (appropriate for neuropathic pain) are excluded, 24.8% of patients still received a potentially inappropriate prescription in 2003. CONCLUSIONS: Prescription of potentially inappropriate medication, particularly benzodiazepines, to older people remains at a high level in the UK. Levels were higher than those seen in published data from the Netherlands, however the low rate of co-proxamol prescribing in the Netherlands explains much, but not all, of the difference. Future international comparisons, based on more careful delineation of the criteria, may play a valuable role in pharmaco-vigilance and can identify areas where regulation of prescribing may reduce risks to older patients.

Aged↗
PubMed2006

The use of primary care databases: case-control and case-only designs.

Study designs based on the identification of cases are frequently utilized when undertaking epidemiological research. Traditionally these have been mainly based on identification of cases from hospital records. This paper discusses the use of study designs based on the identification of cases focusing on their application to research data derived from primary care. The designs are discussed in the context of using computerized clinical data derived from primary care. The traditional case-control design is considered, with emphasis on the identification of cases and the selection of controls. A common problem when using primary care research databases is that information about potential confounding variables is often limited. Case-only designs, specifically the case-crossover and the within-person case-series, offer alternative designs that aim to overcome problems with confounding. The principles underlying these case-only designs are presented along with examples of their use. The advantages and limitations of the different designs are discussed.

Ambulatory Care Information Systems↗
PubMed2006

Does breastfeeding influence risk of type 2 diabetes in later life? A quantitative analysis of published evidence.

BACKGROUND: Observational evidence suggests that having been breastfed in infancy may reduce the prevalence of type 2 diabetes in later life. OBJECTIVE: The objective was to examine the influence of initial breastfeeding on type 2 diabetes and blood glucose and insulin concentrations. DESIGN: A systematic review of published studies identified 1010 reports; 23 examined the relation between infant feeding and type 2 diabetes in later life or risk factors for diabetes. Risk factors in infants were examined separately from those in children and adults. All estimates were pooled by using fixed-effect models; differences <0 and ratios <1 imply a beneficial effect of breastfeeding. RESULTS: Subjects who were breastfed had a lower risk of type 2 diabetes in later life than did those who were formula fed (7 studies; 76 744 subjects; odds ratio: 0.61; 95% CI: 0.44, 0.85; P = 0.003). Children and adults without diabetes who had been breastfed had marginally lower fasting insulin concentrations than did those who were formula fed (6 studies; 4800 subjects; percentage difference: -3%; 95% CI: -8%, 1%; P = 0.13); no significant difference in fasting glucose concentrations was observed. Breastfed infants had lower mean preprandial blood glucose (12 studies; 560 subjects; mean difference: -0.17 mmol/L; 95% CI: -0.28, -0.05 mmol/L; P = 0.005) and insulin (7 studies; 291 subjects; mean difference: -2.86 pmol/L; 95% CI: -5.76, 0.04 pmol/L; P = 0.054) concentrations than did those who were formula fed. CONCLUSION: Breastfeeding in infancy is associated with a reduced risk of type 2 diabetes, with marginally lower insulin concentrations in later life, and with lower blood glucose and serum insulin concentrations in infancy.

Adolescent↗
PubMed2006

A study of TH01 and IGF2-INS-TH haplotypes in relation to smoking initiation in three independent surveys.

OBJECTIVES: Recent studies suggest an association between a microsatellite locus (TH01) located in intron 1 of the tyrosine hydroxylase gene (TH) and nicotine dependence. We aimed here to study whether both TH01 and haplotypes of the wider IGF2-INS-TH region influence initiation of regular smoking in current smokers. METHODS: A total of 3637 individuals from three independent studies (two of adults and one of adolescents) were analysed in relation to the age of first regular smoking (AFRS). Haplotypes and genotypes were obtained for the polymorphisms TH01, IGF2 ApaI, INS HphI and DRD4 VNTR (48 bp)n. Association between IGF2-INS-TH haplotypes and AFRS was tested by a regression model. A genotype-based genetic model assuming additivity was followed in order to estimate the effect of individual loci. RESULTS: Overall, no significant associations were found after correcting for multiple tests. However, an IGF2-INS-TH haplotype (*5) was found to be nominally associated with AFRS at younger ages in adult smokers. Analyses of individual loci points to TH01 as a possible candidate influencing initiation of regular smoking. An AFRS-lowering trend nominally associated with allele 9 in a dosage-dependent manner was identified in both adult cohorts. TH01 did not show association or trend with age of initiation (first puff) either in adolescents or in the adolescents smoking regularly at age 18. CONCLUSION: This study adds to the genetic evaluation of the associations of TH01 with smoking predisposition. Differences between historical and prospective surveys, different biological pathways and possible functional roles of this microsatellite in smoking initiation are discussed.

Genetic Predisposition to Disease↗
PubMed2006

Variations in primary open-angle glaucoma prevalence by age, gender, and race: a Bayesian meta-analysis.

PURPOSE: To quantify the variation in primary open-angle glaucoma (OAG) prevalence with age, gender, race, year of publication, and survey methodology. METHODS: Medline, EMBASE, and PubMed were searched for studies of OAG prevalence. Studies with defined population samplings were sought. Forty-six published observational studies of OAG prevalence (103,567 participants with 2509 cases of OAG) were identified for inclusion in the systematic review and meta-analysis. Data on the number of people and the number of cases of OAG by age, race, and gender were sought for each study. Additional information was obtained regarding whether the definition of glaucoma relied on raised intraocular pressure (IOP) and whether visual field examination was performed routinely on all individuals. Bayesian meta-analysis was used to model the associations between the log odds of OAG and age, race, gender, year of publication, method of visual field testing, and effect of reliance on IOP in the definition of OAG. RESULTS: Black populations had the highest OAG prevalence at all ages, but the proportional increase in prevalence of OAG with age was highest in white populations. The odds ratio per decade increase in age was 2.05 in white populations (95% credible interval, 1.91 to 2.18), 1.61 (95% credible interval, 1.53 to 1.70) in black populations, and 1.57 (95% credible interval, 1.46 to 1.68) in Asian populations. The average estimated prevalence in those older than 70 years of age was 6% in white populations, 16% in black populations, and 3% in Asian populations. After adjusting for age, race, year of publication, and survey methods, men were 1.37 (95% credible interval, 1.22 to 1.53) times more likely than women to have OAG. The prevalence of OAG was one third lower in studies in which routine visual fields were not assessed and that used an IOP criterion in the definition of glaucoma; this effect was reduced to the null after adjustment for age, racial group, and year of publication. CONCLUSIONS: Although black populations had the highest prevalence of OAG at all ages, white populations showed the steepest increase in OAG prevalence with age. Men were more likely than women to have OAG.

Adult↗
PubMed2005

Onset and persistence of depression in older people--results from a 2-year community follow-up study.

BACKGROUND: baseline physical health, disability and social support have been shown to predict depression onset, but findings for persistence are inconsistent. For onset and persistence of depression, the effect of changes in these risk factors over time is unclear. OBJECTIVE: to use baseline factors and change in factors over time to predict onset and persistence of depression over a 2-year period. METHODS: a prospective cohort study with index assessment and 2-year follow-up of patients initially aged > or =65 years registered with two South London practices (n = 1,164). Depression was defined by a score >5/15 on the 15-item Geriatric Depression Scale. Associations between risk factors and onset and persistence of depression were analysed using multiple logistic regression. RESULTS: the incidence of depression was 8.4%, while depression persisted amongst 61.2% of those depressed at baseline. Comparing onset and persistence suggested some common predictors: greater baseline depression score; and follow-up measures of poor general health and compromised social support. There was some evidence that pain and worsening disability were more important for depression onset. In contrast, low baseline belief in powerful others (health locus of control measure) predicted persistence only. CONCLUSION: focusing on older people with increasing disability, pain, physical ill-health and compromised social support should help in both the prevention and recognition of onset of later-life depression. In older people with depression, those with the highest symptom scores and low belief in powerful others at baseline were more likely to develop chronic symptoms and could be targeted for more intensive treatment and support.

Age of Onset↗
PubMed2005

Sex differences in the association between birth weight and total cholesterol. A meta-analysis.

PURPOSE: Determine whether a sex difference exists in the association between birth weight and total cholesterol later in life. METHODS: Meta-analysis of within-study differences in regression coefficients of cholesterol on birth weight. RESULTS: A total of 34 regression coefficients from 30 studies were included in the analyses; these provided data on 33,650 males and 23,129 females. There was evidence that the inverse association between birth weight and total cholesterol was stronger in males compared to females. The pooled within-study difference in age-adjusted regression coefficients was -0.03 mmol/l (-0.06, -0.01), p = 0.02 and the pooled within-study difference in age and body mass index adjusted regression coefficients was -0.04 mmol/l (-0.07, -0.02), p = 0.002. There was no evidence of heterogeneity in these meta-analyses (both p values > 0.6). CONCLUSIONS: These results provide some evidence for a sex difference in the birth weight-total cholesterol association. This is consistent with studies of fetal growth which suggest that birth size reflects different biological processes for females and males. However, other very large studies are required to confirm this finding.

Adolescent↗
PubMed2005

Trends in the prevalence and management of diagnosed type 2 diabetes 1994-2001 in England and Wales.

BACKGROUND: Type 2 diabetes is an important cause of morbidity and mortality. Its prevalence appears to be increasing. Guidelines exist regarding its management. Recommendations regarding drug therapy have changed. Little is known about the influence of these guidelines and changed recommendations on the actual management of patients with type 2 diabetes. This study aims to document trends in the prevalence, drug treatment and recording of measures related to the management of type 2 diabetes; and to assess whether recommended targets can be met. METHODS: The population comprised subjects registered between 1994 and 2001 with 74 general practices in England and Wales which routinely contribute to the Doctors' Independent Network database. Approximately 500,000 patients and 10,000 type 2 diabetics were registered in each year. RESULTS: Type 2 diabetes prevalence rose from 17/1000 in 1994 to 25/1000 in 2001. Drug therapy has changed: use of long acting sulphonylureas is falling while that of short acting sulphonylureas, metformin and newer therapies including glitazones is increasing. Electronic recording of HbA1c, blood pressure, cholesterol and weight have risen steadily, and improvements in control of blood pressure and cholesterol levels have occurred. However, glycaemic control has not improved, and obesity has increased. The percentage with a BMI under 25 kg/m2 fell from 27.0% in 1994 to 19.4% in 2001 (p < 0.001). CONCLUSION: Prevalence of type 2 diabetes is increasing. Its primary care management has changed in accordance with best evidence. Monitoring has improved, but further improvement is possible. Despite this, glycaemic control has not improved, while the prevalence of obesity in the diabetic population is rising.

Adolescent↗
PubMed2005

Are early life factors responsible for international differences in adult blood pressure? An ecological study.

BACKGROUND: Although low birthweight has been related to higher mean blood pressure in individuals, there have been very few studies on the contribution of the 'fetal origins hypothesis' to international variations in mean blood pressure. METHODS: Standardized data on mean blood pressure levels in adults aged 20-29 years (available from the INTERSALT study countries) were related to data on mean birthweight and infant mortality rates (IMRs) approximately 25 years earlier (available from the World Health Organization and the United Nations statistics for 24 of these countries). RESULTS: Population mean systolic pressure was inversely correlated with IMR (r = -0.66, P < 0.001) and positively correlated with mean birthweight (r = 0.36, P = 0.108). These correlations were little affected by adjustment either for current body mass index or for current sodium, potassium, and alcohol intake. CONCLUSIONS: The directions of these associations suggest that low mean birthweight and high infant mortality are not important determinants of high population mean adult blood pressure levels.

Adult↗
PubMed2005

Circulating soluble E-selectin levels and the Ser 128Arg polymorphism in individuals from different ethnic groups.

BACKGROUND AND AIM: An association between the Ser128 Arg polymorphism and coronary heart disease (CHD) has been previously demonstrated in a white population. The aim of this study was to investigate whether the Ser128 Arg polymorphism of the E-selectin gene is associated with soluble E-selectin levels in individuals from a multiethnic population. METHODS AND RESULTS: Plasma sE-selectin levels and the Ser128 Arg E-selectin gene polymorphism were determined in 244 white (109 females), 176 of African origin (90 females) and 208 South Asian (95 females) healthy individuals living in England selected from the Wandsworth Heart and Stroke Study (WHSS). The substitution of serine for arginine (A to C mutation) was more common in whites (9.6%) and South Asians (7.9%) compared to the people of African origin (3.7%); p=0.005. The C mutation had no effect on sE-selectin levels in any ethnic group. CONCLUSIONS: We found a lower frequency of this polymorphism in the people of African origin who have a low CHD risk. However, in this study the polymorphism was not associated with circulating sE-selectin levels. Whether it plays a role in determining ethnic differences in vascular disease via a mechanism affecting leukocyte recruitment remains to be determined.

Age Factors↗
PubMed2005

The effect of breastfeeding on mean body mass index throughout life: a quantitative review of published and unpublished observational evidence.

BACKGROUND: Evidence from observational studies has suggested that breastfeeding may reduce the prevalence of obesity in later life. OBJECTIVE: The objective was to examine whether initial breastfeeding is related to lower mean body mass index (BMI; in kg/m(2)) throughout life. DESIGN: The study was a systematic review of published studies investigating the association between infant feeding and a measure of obesity or adiposity in later life, which was supplemented with data from unpublished sources. Analyses were based on the mean differences in BMI between those subjects who were initially breastfed and those who were formula-fed (expressed as breastfed minus bottle-fed), which were pooled by using fixed-effects models throughout. RESULTS: From 70 eligible studies, 36 mean differences in BMI (from 355 301 subjects) between those breastfed and those formula-fed (reported as exclusive feeding in 20 studies) were obtained. Breastfeeding was associated with a slightly lower mean BMI than was formula feeding (-0.04; 95% CI: -0.05, -0.02). The mean difference in BMIs appeared larger in 15 small studies of <1000 subjects (-0.19; 95% CI: -0.31, -0.08) and smaller in larger studies of >or=1000 subjects (-0.03; 95% CI: -0.05, -0.02). An Egger test was statistically significant (P = 0.002). Adjustment for socioeconomic status, maternal smoking in pregnancy, and maternal BMI in 11 studies abolished the effect (-0.10; 95% CI: -0.14, -0.06 before adjustment; -0.01; 95% CI: -0.05, 0.03 after adjustment). CONCLUSIONS: Mean BMI is lower among breastfed subjects. However, the difference is small and is likely to be strongly influenced by publication bias and confounding factors. Promotion of breastfeeding, although important for other reasons, is not likely to reduce mean BMI.

Adult↗
PubMed2005

CYP2A6, MAOA, DBH, DRD4, and 5HT2A genotypes, smoking behaviour and cotinine levels in 1518 UK adolescents.

OBJECTIVES: Smoking is a major cause of death and often initiates in adolescence. Mutations in CYP2A6 slow metabolism of nicotine to cotinine. Haploinsufficiency in adults is associated with lower cigarette consumption, lower cotinine level and higher quit rates. Other genes are also implicated in smoking behaviour. We explored smoking behaviour and cotinine levels in relation to genotypes in adolescents. METHODS: 1518 subjects from the Ten Towns Heart Health Study were genotyped for CYP2A6 alleles *1A, *1B, *2, *4, *5, *9 and *12 to classify predicted nicotine metabolism rate. DBH(rs77905), MAOA(rs1801291+VNTR), DRD4(VNTR) and 5HT2A(rs6313) were also studied. Smoking status was established by questionnaire and salivary cotinine measurement at 13-15 and 18 years. RESULTS: No significant associations were identified for DBH, MAOA, DRD4 and 5HT2A markers, with smoking status or cotinine level at either age. At age 18, haploinsufficiency (HI) for CYP2A6 was associated with a higher odds of being a current smoker compared with the *1B carriers (WT1B) (OR = 2.23 (1.16, 4.27) for current versus ex); *1A homozygotes (WT1A) were also at slightly higher risk (OR = 1.44 (1.01, 2.06)). Partial haploinsufficiency (PHI) was not associated with being a current smoker. There were no significant associations at age 13-15. PHI and HI were associated with higher cotinine levels amongst smokers at both 13-15 and at 18 years compared with WT1B and WT1A groups. CONCLUSIONS: CYP2A6 haploinsufficiency increases likelihood of continuing smoking in teenagers. We hypothesize an explanatory 'occupancy' model to explain why haploinsufficiency results in faster progression to nicotine dependence, but lower subsequent consumption.

Adolescent↗
PubMed2005

Effect of infant feeding on the risk of obesity across the life course: a quantitative review of published evidence.

OBJECTIVE: To examine the influence of initial infant feeding on obesity in later life. METHODS: A systematic review of published studies investigating the association between infant feeding and a measure of obesity was performed with Medline (1966 onward) and Embase (1980 onward) databases, supplemented with manual searches. Data extraction was conducted by 2 authors. Analyses were based on odds ratios of obesity among initially breastfed subjects, compared with formula-fed subjects, pooled with fixed-effects models. RESULTS: Sixty-one studies reported on the relationship of infant feeding to a measure of obesity in later life; of these, 28 (298900 subjects) provided odds ratio estimates. In these studies, breastfeeding was associated with a reduced risk of obesity, compared with formula feeding (odds ratio: 0.87; 95% confidence interval [CI]: 0.85-0.89). The inverse association between breastfeeding and obesity was particularly strong in 11 small studies of <500 subjects (odds ratio: 0.43; 95% CI: 0.33-0.55) but was still apparent in larger studies of > or =500 subjects (odds ratio: 0.88; 95% CI: 0.85-0.90). In 6 studies that adjusted for all 3 major potential confounding factors (parental obesity, maternal smoking, and social class), the inverse association was reduced markedly (from an odds ratio of 0.86 to 0.93) but not abolished. A sensitivity analysis examining the potential impact of the results of 33 published studies (12505 subjects) that did not provide odds ratios (mostly reporting no relationship between breastfeeding and obesity) showed little effect on the results. CONCLUSIONS: Initial breastfeeding protects against obesity in later life. However, a further review including large unpublished studies exploring the effect of confounding factors in more detail is needed.

Breast Feeding↗
PubMed2004

Birth weight and subsequent cholesterol levels: exploration of the "fetal origins" hypothesis.

CONTEXT: Inverse associations between birth weight and subsequent blood cholesterol levels have been used to support the "fetal origins" hypothesis of the relevance of fetal nutrition to adult disease. OBJECTIVES: To perform a systematic review of the association between birth weight and total blood cholesterol levels, and to explore the impact of including unpublished results, adjusting for potential confounders. DATA SOURCES AND STUDY SELECTION: Relevant studies published by September 30, 2004, were identified through literature searches using EMBASE and MEDLINE and MeSH heading search strategy (using terms such as birth weight, intrauterine growth retardation, fetal growth retardation and cholesterol, lipoprotein, lipid). Studies that reported qualitative or quantitative estimates of the association between birth weight and total blood cholesterol, or had recorded both measures but not reported on their associations, were included. DATA EXTRACTION: A total of 79 relevant studies involving a total of 74,122 individuals were identified; 65 had reported on the direction of the association between birth weight and total blood cholesterol. Although regression coefficients were published for only 11 studies and other quantitative estimates for 3 other studies, regression coefficients (published or unpublished) were obtained for 58 studies among 68,974 individuals. DATA SYNTHESIS: Inverse associations were observed in 11 of 14 studies that had previously published quantitative estimates but in only 18 of the remaining 51 that had reported on the direction of this association (heterogeneity P = .004). Similarly, the weighted estimate for the 11 studies was -1.89 mg/dL (-0.049 mmol/L) total cholesterol per kilogram birth weight compared with -0.69 mg/dL (-0.018 mmol/L) per kilogram for 47 studies that provided unpublished regression coefficients (heterogeneity P = .009). Overall, the weighted estimate from the 58 contributing studies was -1.39 mg/dL (-0.036 mmol/L) per kilogram (95% confidence interval, -1.81 to -0.97 mg/dL [-0.047 to -0.025 mmol/L]), but there was significant heterogeneity between their separate results (P<.001). Part of this heterogeneity appears to reflect stronger associations reported from smaller studies and studies of cholesterol levels in infants. CONCLUSION: These findings suggest that impaired fetal growth does not have effects on blood cholesterol levels that would have a material impact on vascular disease risk.

Adult↗
PubMed2004

Passive smoking and risk of coronary heart disease and stroke: prospective study with cotinine measurement.

OBJECTIVE: To examine the associations between a biomarker of overall passive exposure to tobacco smoke (serum cotinine concentration) and risk of coronary heart disease and stroke. DESIGN: Prospective population based study in general practice (the British regional heart study). PARTICIPANTS: 4729 men in 18 towns who provided baseline blood samples (for cotinine assay) and a detailed smoking history in 1978-80. MAIN OUTCOME MEASURE: Major coronary heart disease and stroke events (fatal and non-fatal) during 20 years of follow up. RESULTS: 2105 men who said they did not smoke and who had cotinine concentrations < 14.1 ng/ml were divided into four equal sized groups on the basis of cotinine concentrations. Relative hazards (95% confidence intervals) for coronary heart disease in the second (0.8-1.4 ng/ml), third (1.5-2.7 ng/ml), and fourth (2.8-14.0 ng/ml) quarters of cotinine concentration compared with the first (> or = 0.7 ng/ml) were 1.45 (1.01 to 2.08), 1.49 (1.03 to 2.14), and 1.57 (1.08 to 2.28), respectively, after adjustment for established risk factors for coronary heart disease. Hazard ratios (for cotinine 0.8-14.0 nu > or = 0.7 ng/ml) were particularly increased during the first (3.73, 1.32 to 10.58) and second five year follow up periods (1.95, 1.09 to 3.48) compared with later periods. There was no consistent association between cotinine concentration and risk of stroke. CONCLUSION: Studies based on reports of smoking in a partner alone seem to underestimate the risks of exposure to passive smoking. Further prospective studies relating biomarkers of passive smoking to risk of coronary heart disease are needed.

Adult↗
PubMed2004

Developing a large electronic primary care database (Doctors' Independent Network) for research.

BACKGROUND AND OBJECTIVES: Primary care databases form a unique source of population-based clinical information on the prevalence and management of diagnosed disorders. Historically such databases have lacked individual level socio-economic markers. We describe the development of the Doctors' Independent Network (DIN) database for epidemiological and health services research. DIN includes a socio-economic marker (ACORN) based on postcode linkage at individual patient level. The validity of DIN is assessed against the General Practice Research Database (GPRD). METHODS: External validity is assessed by comparing the demographic structure and prevalence rates for treated ischemic heart disease (IHD) and treated hay fever with those from the GPRD. We assess the utility of a socio-economic measure (ACORN) based on postcode-linkage at individual patient level by examining the trend in prevalence rates of IHD and hay fever by ACORN index. RESULTS: 142 practices providing high quality data were selected, with 1827361 fully registered patients contributing data between 1992 and 2001, representing an identical age-sex structure to that for England & Wales and GPRD. Regionally adjusted prevalence of treated IHD (7.29 and 5.37%, respectively for men and women aged 35+ in 1998) in DIN was highly comparable to GPRD (7.27 and 5.42%). In DIN, the odds ratio of IHD was 1.37 (95% CI 1.30-1.44) in subjects living in "striving" compared to "thriving" areas. The prevalence of treated hay fever prevalence was similar across databases, with inverse associations seen with ACORN in DIN (higher rates in "thriving" areas). CONCLUSIONS: DIN provides comparable period prevalence rates to GPRD for two common conditions, with social trends as expected. Primary care databases such as these have the potential to replace the decennial national morbidity surveys carried out in UK general practices, with DIN having the important advantage of including a socio-economic index.

Adolescent↗