Biomedical subjects

David P Strachan

Publications and source records attributed to David P Strachan.

24 records · Page 2Linked to original sources

PubMed2004

Natural history of atopic dermatitis and its relationship to serum total immunoglobulin E in a population-based birth cohort study.

We investigated the natural history of atopic dermatitis (AD) in a population-based birth cohort and assessed whether children at risk of visible eczema at 5 years of age can be identified from total immunoglobulin E (IgE) levels measured at 8, 12 and 18 months. AD data collected included a whole body examination for visible eczema at 49 months (4 years) and 61 months (5 years) of age and parent completed questionnaire data throughout their early lives. Children were divided into four groups based on their natural history of early AD: persistent (AD at 1, 6, 18, 30 and 42 months, n = 34), intermittent early onset (before 18 months of age, n = 495), intermittent late onset (18-42 months of age, n = 273) and unaffected (n = 429). Visible eczema at 5 years of age was present in 12.2% (117/957) (95% confidence interval [CI] 10.1-14.3%) of the children. Levels of total IgE at 8, 12 and 18 months of age were associated with early onset of AD, but not with AD of later onset. For all four natural history groups, the geometric mean total IgE at 12 months was higher in those who subsequently had visible eczema than those who did not. However, the degree of overlap was such that total IgE at 12 months of age was a poor predictor of eczema at age five. A cutoff point of 78 kU/l had the highest positive predictive value for visible eczema at 5 years of age of 28.6%, with a sensitivity of 12% and specificity of 95%.

Age Factors↗

PubMed2004

Analysis of the vitamin D receptor gene sequence variants in type 1 diabetes.

Vitamin D is known to modulate the immune system, and its administration has been associated with reduced risk of type 1 diabetes. Vitamin D acts via its receptor (VDR). Four single nucleotide polymorphisms (SNPs) of the VDR gene have been commonly studied, and evidence of association with type 1 diabetes has been reported previously. We sequenced the VDR gene region and developed its SNP map. Here we analyzed association of the 98 VDR SNPs in up to 3,763 type 1 diabetic families. First, we genotyped all 98 SNPs in a minimum of 458 U.K. families with two affected offspring. We further tested eight SNPs, including four SNPs associated with P < 0.05 in the first set and the four commonly studied SNPs, in up to 3,305 additional families from the U.K., Finland, Norway, Romania, and U.S. We only found weak evidence of association (P = 0.02-0.05) of the rs4303288, rs12721366, and rs2544043 SNPs. We then tested these three SNPs in an independent set of 1,587 patients and 1,827 control subjects from the U.K. and found no evidence of association. Overall, our results indicate that common sequence variation in the VDR gene has no major effect in type 1 diabetes in the populations tested.

Diabetes Mellitus, Type 1↗

PubMed2004

Replication of an association between the lymphoid tyrosine phosphatase locus (LYP/PTPN22) with type 1 diabetes, and evidence for its role as a general autoimmunity locus.

In the genetic analysis of common, multifactorial diseases, such as type 1 diabetes, true positive irrefutable linkage and association results have been rare to date. Recently, it has been reported that a single nucleotide polymorphism (SNP), 1858C>T, in the gene PTPN22, encoding Arg620Trp in the lymphoid protein tyrosine phosphatase (LYP), which has been shown to be a negative regulator of T-cell activation, is associated with an increased risk of type 1 diabetes. Here, we have replicated these findings in 1,388 type 1 diabetic families and in a collection of 1,599 case and 1,718 control subjects, confirming the association of the PTPN22 locus with type 1 diabetes (family-based relative risk (RR) 1.67 [95% CI 1.46-1.91], and case-control odds ratio (OR) 1.78 [95% CI 1.54-2.06]; overall P = 6.02 x 10(-27)). We also report evidence for an association of Trp(620) with another autoimmune disorder, Graves' disease, in 1,734 case and control subjects (P = 6.24 x 10(-4); OR 1.43 [95% CI 1.17-1.76]). Taken together, these results indicate a more general association of the PTPN22 locus with autoimmune disease.

Adult↗

PubMed2003

Implications of the problem orientated medical record (POMR) for research using electronic GP databases: a comparison of the Doctors Independent Network Database (DIN) and the General Practice Research Database (GPRD).

BACKGROUND: The General Practice Research Database (GPRD) and Doctor's Independent Network Database (DIN), are large electronic primary care databases compiled in the UK during the 1990s. They provide a valuable resource for epidemiological and health services research. GPRD (based on VAMP) presents notes as a series of discrete episodes, whereas DIN is based on a system (MEDITEL) that used a Problem Orientated Medical Record (POMR) which links prescriptions to diagnostic problems. We have examined the implications for research of these different underlying philosophies. METHODS: Records of 40,183 children from 141 practices in DIN and 76,310 from 464 practices in GRPD who were followed to age 5 were used to compare the volume of recording of prescribing and diagnostic codes in the two databases. To assess the importance and additional value of the POMR within DIN, the appropriateness of diagnostic linking to skin emollient prescriptions was investigated. RESULTS: Variation between practices for both the number of days on which prescriptions were issued and diagnoses were recorded was marked in both databases. Mean number of "prescription days" during the first 5 years of life was similar in DIN (19.5) and in GPRD (19.8), but the average number of "diagnostic days" was lower in DIN (15.8) than in GPRD (22.9). Adjustment for linkage increased the average "diagnostic days" to 23.1 in DIN. 32.7% of emollient prescriptions in GPRD appeared with an eczema diagnosis on the same day compared to only 19.4% in DIN; however, 86.4% of prescriptions in DIN were linked to an earlier eczema diagnosis. More specifically 83% of emollient prescriptions appeared under a problem heading of eczema in the 121 practices that were using problem headings satisfactorily. CONCLUSION: Prescribing records in DIN and GPRD are very similar, but the usage of diagnostic codes is more parsimonious in DIN because of its POMR structure. Period prevalence rates will be underestimated in DIN unless this structure is taken into account. The advantage of the POMR is that in 121 of 141 practices using problem headings as intended, most prescriptions can be linked to a problem heading providing a specific reason for their issue.

Child, Preschool↗

PubMed2002

A population-based case-control study for examining early life influences on geographical variation in adult mortality in England and Wales using stomach cancer and stroke as examples.

BACKGROUND: Geographical variation in mortality is influenced by factors operating in early life and in adulthood. The relative contributions of these factors may be examined by comparing the extent to which adult mortality is related to places of residence in early life and at death. We describe a population-based case-control design, in which all deaths are used as cases and the Office for National Statistics (ONS) Longitudinal Study (LS) survivors are used as controls. METHODS: Cases were all deaths from stomach cancer and stroke in England and Wales 1993-1995 amongst people born between January 1930 and September 1939 and for whom place of enumeration in 1939 could be imputed from the first three characters of their National Health Service number. Controls were all LS members born in the same period, enumerated in the 1991 census, resident in England and Wales in mid-1994 and for whom place of enumeration in 1939 could be similarly imputed. Logistic regression was used, adjusting for birth year, sex and social class. A previous mapping exercise by ONS generated comparable geographical units (counties) for 1939 enumeration and area of residence in 1991 or at death. 'Non-migrant' (i.e. 1939 'county' the same as county in 1991 or at death) case:control ratios were calculated to indicate background mortality risk in counties, with adjustment for imprecision using Bayesian smoothing methods. These ratios were then used in modelling risk for inter-county migrants. RESULTS: There were 2590 stomach cancer and 7778 stroke deaths and 28,400 men and 28,180 women as controls. For men, 64%, 61% and 67% of stomach cancer deaths, stroke deaths and controls respectively could be assigned a county of enumeration in 1939. The corresponding percentages for women were 76%, 72% and 75%. For stomach cancer, after adjustment for county of enumeration in 1939, a significant association with the non-migrant case:control ratio for county of residence in 1991 or at death was observed (P= 0.010), indicating an association between current area of residence and stomach cancer mortality. There was no evidence of an independent effect of county of enumeration in 1939. For stroke, there was a highly significant trend in relation to 1939 county (P = 0.0004)and a less significant association with county of residence in 1991 or at death(P = 0.016). CONCLUSIONS: The method described is able to detect the effect of place of residence in early life on geographical variation in adult mortality and will be useful for investigating specific characteristics of areas of enumeration in 1939 in relation to subsequent risk of mortality from a range of diseases.

Case-Control Studies↗

PubMed2002

Association between migraine and asthma: matched case-control study.

BACKGROUND: Earlier studies have suggested a link between asthma and severe headache, and also between migraine and wheezing illness. Recent analysis have also shown an increase of asthma among cases with a prior history of migraine but without a history of hay fever, allergic rhinitis or eczema. AIM: To examine whether there is an association between migraine and asthma in the United Kingdom. DESIGN OF STUDY: Matched case-control study using the General Practice Research Database (GPRD). SETTING: Practices in the United Kingdom providing data on 5,110,619 patients to the GPRD. METHOD: The subjects were the patients with one or more diagnoses of migraine plus treatment for migraine. Each case was matched by general practice, sex, and age, with one control who had never been given a diagnosis of migraine. Case and control groups were compared for prevalence of asthma, chronic obstructive pulmonary disease, respiratory symptoms treated with inhalers or hay fever. Investigations were carried out to determine whether the association between migraine and asthma was stronger among patients with hayfever or those without hayfever, and whether patients with migraine had an increased prescription of other (non-migraine and non-asthma) medications. RESULTS: Among 64 678 case-control pairs, the relative risk of asthma in patients with migraine was 1.59 (95% CI = 1.54 to 1.65) among definite cases, and 0.75 (95% CI = 0.67 to 0.83) among those whose selection as case included beta-blocker prophylaxis. Among definite migraine cases, relative risks of chronic obstructive pulmonary disease, respiratory symptoms, eczema, and hay fever (pollinosis), were all raised (at 1.22, 1.85, 1.55, and 1.67, respectively). The association between migraine and asthma was stronger in patients without a diagnosis of hay fever, than in those with hayfever (relative risk = 1.32 and 1.19, respectively). The relative risk of prescription for a range of non-migraine, non-asthma medications was raised, the exception being anti-diabetic medication. CONCLUSION: This large case-control study provides evidence for an association between migraine and asthma. Frequent attendance at a general practice surgery may confound this association. However, if the association is real, its elucidation may help the understanding of disease mechanisms shared by migraine and asthma.

Asthma↗