Infections presenting for clinical care in early life and later risk of hay fever in two UK birth cohorts.

BACKGROUND: The 'hygiene hypothesis' proposes that infections in infancy protect against hay fever (HF). We investigated infections during infancy in relation to HF, including rarer ones not previously researched in this context, while examining the role of potential confounding variables. METHODS: From birth cohorts derived within the General Practice Research Database (GPRD) and Doctors Independent Network (DIN) database of computerized patient records from UK general practice, we selected 3549 case-control pairs, matched for practice, age, sex and control follow-up to case diagnosis. Conditional logistic regressions were fitted for each of 30 infections; behavioural problems (BP) acted as a control condition unrelated to HF. Odds ratios (OR), adjusted for consultation frequency were pooled across the databases using fixed effect models. We also adjusted for sibship size in GPRD and a socioeconomic marker in DIN. RESULTS: Upper respiratory tract infections, diarrhoea and vomiting and acute otitis media in infancy were each related with a moderately increased risk of HF in both databases, as were BP. These associations were lost on adjustment for consultation frequency. Only bronchiolitis was significantly associated with a reduced pooled risk of HF after adjustment for consultations (OR = 0.8). Adjustment for sibship size in GPRD and a socioeconomic marker in DIN had little impact on the OR. CONCLUSIONS: Of 30 infectious illnesses investigated, none had strong or consistent associations with HF after adjustment for consultation frequency. Except for bronchiolitis, possibly a chance finding, none of the clinically apparent infections considered appear to have an important role in allergy prevention.

Vaccinations, infections and antibacterials in the first grass pollen season of life and risk of later hayfever.

BACKGROUND: It has been hypothesized that early-life exposure to vaccinations, infections or antibacterials influence allergic disease development. Concurrent exposure to grass pollens may alter any effect. OBJECTIVE: To test the hypothesis that exposure to antibacterials, vaccinations (DTP or MMR) or specific infections during the first grass pollen seasons of life influences the risk of hayfever more than at any other time of the year. METHODS: Nested case-control studies were based on birth cohorts within two large databases of computerized patient records from UK general practices: the General Practice Research Database (GPRD) and Doctors' Independent Network (DIN). Seven thousand ninety-eight hayfever cases, diagnosed after age 2, were matched to controls for practice, age, sex and follow-up of control to case ascertainment date. Conditional logistic regression was used to compare exposure by age 1 (age 2 for MMR) inside vs. outside the grass pollen season (May, June, July). Odds ratios (ORs) were pooled across databases. RESULTS: There were no associations in either database between MMR during vs. outside the grass pollen season and later hayfever. Of 23 infections studied, none were statistically significant; although analyses for the less common conditions were limited by low statistical power. The pooled OR for hayfever comparing exposure to antibacterials only in the grass pollen season with only outside it was 1.20 (95% CI 0.98-1.47) and for DTP was 0.84 (95% CI 0.72-0.98). CONCLUSION: Although an interaction between early exposure to microbial agents and concurrent grass pollen exposure on hayfever risk seemed plausible, there was little evidence to support it across a range of analyses. However, the effect of DTP though weak deserves further study.

Timing of routine immunisations and subsequent hay fever risk.

BACKGROUND: Suggestions that immunisation influences allergic disease risk, either positively (pertussis) or negatively (BCG) are of concern for vaccination policy. AIMS: To determine whether DTP, MMR, and BCG vaccination in infancy influenced hay fever risk. METHODS: Case-control study of 7098 hay fever cases and controls, within two primary care databases. One control per case was matched for practice, age, and sex. Odds ratios (OR) were derived using conditional logistic regression. RESULTS: Compared to those completing in month 5 (base group) (39.3%), DTP unvaccinated children (4.3%) had a similar risk of hay fever (OR = 0.94, 95% CI 0.73 to 1.23). However, those completing after 12 months (4.2%) had a reduced risk (OR = 0.60, 95% CI 0.45 to 0.76) compared to the base group. Compared to those vaccinated in month 14 (base group) (29.5%), MMR unvaccinated children (2.3%) had an OR of 0.79 (95% CI 0.58 to 1.08). Completion of MMR after two years was associated with reduced hay fever risk (OR = 0.62, 95% CI 0.48 to 0.80) compared to the base group. The effects of late immunisation with DTP and MMR were independent. Those vaccinated with BCG by age 2 (2.4%) had an odds ratio of 1.28 (95% CI 0.96 to 1.70). Adjustment for consulting behaviour, social factors, or sibship size did not alter these associations. CONCLUSIONS: Immunisation against DTP or MMR does not increase the risk of hay fever. The lower confidence limit for BCG vaccination contradicts the hypothesised protective effect. The reduced risk of hay fever among children immunised late may be explained by a third factor causing both postponement and reduced risk such as intercurrent febrile illnesses.

A comparison of the recording of 30 common childhood conditions in the Doctor's Independent Network and General Practice Research Databases.

In this article we compare the recording of 30 common childhood conditions in two general practice databases of anonymised computerised medical records based on fundamentally different systems--the Doctor's Independent Network (DIN) database (Torex system) and the General Practice Research Database (GPRD) (In Practice Systems). Analysing the records of all children born 1990-1993 and followed for 5 years we found comparable results for most conditions, but differences between the hierarchical structures of the diagnostic coding systems (Read in DIN, OXMIS in GPRD) led to some differences between the databases. Practice variation was marked, but comparable between databases. Variation was greatest in conditions that are poorly defined clinically.

Early-life exposure to antibacterials and the subsequent development of hayfever in childhood in the UK: case-control studies using the General Practice Research Database and the Doctors' Independent Network.

BACKGROUND: Theoretically, antibacterial agents in early life might influence allergic sensitization in two ways: (i) as an indicator of infectious illness, they might be expected to protect against allergy; (ii) alternatively they might increase the risk through effects on the commensal bowel flora. Epidemiological evidence linking the prescription of antibacterial agents in early life to the subsequent development of hayfever is conflicting. OBJECTIVE: To establish definitively whether an association exists between early-life antibacterial exposure and childhood hayfever diagnosis. METHODS: Nested case-control studies were based on birth cohorts of children identified within two large UK general practice databases of electronic patient records. One hundred and sixteen thousand and four hundred and ninety-three children from 605 general practices were identified as being continuously registered from birth to at least age 5 years. Seven thousand and ninety-eight cases were diagnosed with hayfever after the age of 2 years. One control per case was matched for practice, birth month, sex and still being registered on case diagnosis date. Odds ratios were derived from conditional logistic regressions within each database followed by pooling using a fixed-effect model. RESULTS: The pooled odds ratio for hayfever was 1.11, 95% CI (1.03-1.20) if exposed to antibacterials in the first year of life, 1.35 (1.25-1.46) in year 2 and 1.47 (1.37-1.59) in year 3. Adjusting for consultation frequency reduced these odds ratios to 0.92, 1.05 and 1.10, respectively. There was no evidence that broader spectrum antibacterials, exposure in any specific month of year 1 or in the grass pollen season influenced the risk of hayfever. CONCLUSION: These data exclude any important effect of antibacterial exposure in infancy on subsequent hayfever risk. Associations reported in earlier studies have likely been exaggerated through publication bias and by lack of control for the tendency of some families to consult frequently for a range of conditions.

Evolution of statin prescribing 1994-2001: a case of agism but not of sexism?

OBJECTIVE: To study trends in the use of lipid lowering drugs in the UK, and to assess which patient factors influence prescribing. METHODS: Routinely collected computerised medical data were analysed from 142 general practices across England and Wales that provide data for the Doctors' Independent Network database. Subjects included were people aged 35 years or more with treated ischaemic heart disease, averaging annually over 30,000. The temporal trend from 1994 to 2001 in prescription of lipid lowering drugs and daily statin dose and the odds ratios (ORs) for receiving a statin prescription in 1998 were examined. RESULTS: Lipid lowering drug prescribing increased greatly over time, entirely because of statins, so that in 2001 56.3% of men and 41.1% of women with ischaemic heart disease received lipid lowering drugs. However, 33% of these patients were on a < 20 mg simvastatin daily equivalent. In 1998 the OR for receiving a statin fell from 1 at age 55-64 to 0.64 at 65-74 and 0.16 at 75-84 years. The age effect was similar in those without major comorbidity. Revascularised patients were much more likely to receive a statin than those with angina (OR 3.92, 95% confidence interval (CI) 3.57 to 4.31). Men were more likely to receive a statin than women (OR 1.62, 95% CI 1.54 to 1.71) but this difference disappeared after adjustment for age and severity of disease (OR 1.06). Geographical region had little effect but there was a very weak socioeconomic gradient. CONCLUSIONS: Although prescribing has increased, many patients who may benefit from lipid lowering drugs either do not receive it or are undertreated, possibly because of lack of awareness of the relative potency of the different statins. Patients with angina and the elderly are less likely to receive treatment that may prevent a coronary event.

Do children who become autistic consult more often after MMR vaccination?

A close temporal association has been reported between the measles, mumps, and rubella (MMR) vaccination and dramatic behavioural decline in children subsequently diagnosed as autistic. We hypothesised that such a decline would be reflected in increased consultations with the child's general practitioner. The Doctor's Independent Network database was used to examine whether children subsequently diagnosed as autistic consulted more frequently than controls after MMR vaccination. No difference in consulting behaviour was seen in the six months post MMR. Any dramatic effect of MMR on behaviour seems unlikely.

Trends in prescribing H2-receptor antagonists and proton pump inhibitors in primary care.

BACKGROUND: H2-receptor antagonists and proton pump inhibitors account for approximately 15% of primary care prescribing costs in the UK. AIM: To examine the use of antisecretory drugs in primary care between October 1991 and September 1996. METHOD: Analysis of prescribing data from an ongoing postal survey performed every 3 months on a rolling quota of 250 UK general practitioners (GPs), identified from a representative sampling frame of 1000 GPs. RESULTS: There were 8811 new courses of proton pump inhibitors and 11,948 new courses of H2-receptor antagonists during this study. The number of new prescriptions for proton pump inhibitors increased by 174.5%, but decreased for H2-receptor antagonists by 12.5%. Proton pump inhibitors were mostly prescribed for reflux disease (52.7%) and H2-receptor antagonists for non-specific dyspepsia (43.6%). Proton pump inhibitors (14.1%) were less likely to be stopped than H2-receptor antagonists (35.3%) overall, and they were less likely to be stopped because of perceived ineffectiveness (5.3%) than H2-receptor antagonists (23.8%). The rate of stopping treatment because of side-effects was about 3% for both classes of drug. CONCLUSIONS: Prescribing of proton pump inhibitors has increased sharply each year since 1991. One reason may be that GPs perceive proton pump inhibitors to be more effective than H2-receptor antagonists.

The impact of the October 1995 'pill scare' on oral contraceptive use in the United Kingdom: analysis of a general practice automated database.

OBJECTIVES: We aimed to measure the change in prescribing of oral contraceptives after the October 1995 UK 'pill-scare'. DESIGN: Analysis was undertaken of an automated database of 100 general practices (372 doctors) in England, Scotland and Wales which use the AAH Meditel computer system. Analysis involved two stages. First, we reviewed prescribing of oral contraceptives at three time periods: before the scare (18.10.95); the following three months (19.10.95-18.1.96); and 3-6 months post-scare (19.1.96-18.4.96). Second, we examined the cohort of women on the pill at the time of the scare to assess discontinuation rates and pill switches after 6 months. RESULTS: Six months after the scare the proportion of women between 16 and 50 years of age prescribed any contraceptive pill decreased by only 3.5% (95% confidence limits: 2.2%-4.8%). The proportion of pill-users prescribed third generation pills decreased from 53.4% to 18.1%, while prescribing of second generation pills increased from 20.1% to 48.4%. The proportion of women currently on third or second generation pills at the time of the scare, who were no longer prescribed any pill after 6 months, was the same as for the equivalent period in the previous year. CONCLUSIONS: The number of women prescribed the pill did not alter markedly after the pill-scare. The main change was a switch from third to second generation pill types. In any future pill-scare women should be warned about the risk of pill-failure if the correct procedure for switching pills is not followed.

Initial treatment choices, second-line therapy, and reasons for stopping medication in the treatment of hypertension by general practitioners in England, Scotland and Wales: 1990-1995.

Information on general practitioners' choices of initial and second-line antihypertensive treatment, and reasons for stopping therapy, are limited. We analysed data on the use of the four main classes of antihypertensive drugs (diuretics, beta-blockers, calcium antagonists and angiotensin-converting enzyme inhibitors) between 1990 and 1995 from an ongoing cross-sectional postal survey of general practitioners' prescribing activity (the New and Change Therapy Enquiry). There were 18,092 new courses and 9424 discontinuations between 1990 and 1995. Diuretics were the commonest first-line choice. Use of beta-blockers first-line decreased significantly in comparison with diuretics during the study period. Switches to calcium antagonists and angiotensin-converting enzyme inhibitors increased. The increased use of newer agents was not explained by increased use for concomitant conditions (diabetes or cardiovascular disease). Diuretics were most often discontinued because of poor efficacy (44% of diuretic stops). In contrast, most beta-blockers (55%), calcium antagonists (64%) and angiotensin-converting enzyme inhibitors (60%) were stopped because of side-effects. In conclusion, use of beta-blockers first-line decreased. Switches to calcium antagonists and angiotensin-converting enzyme inhibitors increased. The reasons may be due to greater perceived efficacy of newer agents rather than increased use for concomitant conditions.

General practitioners' perceptions of the tolerability of antidepressant drugs: a comparison of selective serotonin reuptake inhibitors and tricyclic antidepressants.

OBJECTIVE: To examine inceptions and discontinuations of antidepressants in general practice. DESIGN: An observational study analysing data from an ongoing cross sectional postal survey. Every three months a representative sample of 250 doctors recorded prescribing activity for four weeks. This provided 4000 general practitioner weeks of recording per year. SETTING: A representative panel of general practitioners in England, Wales, and Scotland. SUBJECTS: Patients who began a new course of an antidepressant or had their treatment stopped or changed by the general practitioner between 1 July 1990 and 30 June 1995. MAIN OUTCOME MEASURES: Numbers of patients prescribed a new course of antidepressant; numbers discontinuing treatment; the ratio of antidepressant discontinuations to antidepressant inceptions; reasons for discontinuation; proportion of switches to another antidepressant. RESULTS: There were 13,619 inceptions and 3934 discontinuations of selective serotonin reuptake inhibitors and tricyclic antidepressants during the study. The number of newly prescribed courses of antidepressants increased by 116%, mostly due to an increase in prescribing of serotonin reuptake inhibitors. The ratio of total discontinuations to inceptions was significantly lower for serotonin reuptake inhibitors (22%) than for tricyclic antidepressants (33%). Differences persisted when controlled for age and sex of patients and severity of depression. However, there was more switching away from selective serotonin reuptake inhibitors when they failed (72%) than from tricyclic antidepressants (58%). CONCLUSIONS: Selective serotonin reuptake inhibitors are less likely than tricyclic antidepressants to be discontinued. A prospective study is needed in general practice to assess the implications of differences in discontinuation rates and switches on clinical and economic outcomes.

Prevention in practice: results of a 2-year follow-up of routine health promotion interventions in general practice.

BACKGROUND: The effectiveness of health promotion activity in general practice on risk factor reduction for coronary heart disease remains the subject of active debate. OBJECTIVE: The study aimed to assess the impact of practice-based health check-ups on health behaviours over a 2-year period. METHOD: A general practice cohort of 7123 patients from 18 practices was surveyed. Eight hundred and forty (12%) patients had been offered a health check within a 12-month period from September 1992 and 621 (9%) received one. Two hundred and fifty patients (40%) were asked back for follow-up after their health check. RESULTS: Over a 2-year period there was no difference in smoking cessation, alcohol consumption, weight loss nor the amount of exercise taken between those who attended for a health check and those who did not. The food score chosen to assess dietary change (Oxcheck) showed a statistically significant 1.16-point rise for the whole sample over the survey period. There was a significant difference in mean food score change between health check attenders and non-attenders (Mann-Whitney U test: P < 0.002). Maintenance of dietary improvement over a 2-year period was not affected by health check attendance. CONCLUSIONS: This study confirms the low impact of health checks on the self reported modification of cardiovascular risk factors and shows that maintenance of appropriate health behaviour change is no more likely in those who have received a health check.

A computer-assisted telephone interview technique for assessment of asthma morbidity and drug use in adult asthma.

This study concerns an analysis of the feasibility, validity, and repeatability of telephone interviews for the collection of data concerning health-related quality of life in asthma and patient reports of their use of asthma therapy. A computer-assisted hierarchical interview algorithm was developed that allowed rapid and precise recording of all aspects of asthma medication including drug, dose, and delivery system. This questionnaire was used together with the Symptoms and Impacts components of the St. George's Respiratory Questionnaire (SGRQ) in one face-to-face and then in three computer-assisted telephone interviews (CATIs) that took place 1, 3, and 13 weeks later. One hundred patients with asthma who had received inhaled steroids within the previous year were identified from general practice records. The intraclass correlation between the face-to-face interview and the first CATI for the SGRQ scores and the daily dose of inhaled steroid was approximately 0.8. For daily bronchodilator use, this value was 0.56. The intraclass correlation obtained between two CATIs 3 months apart was a little lower: SGRQ scores, 0.78; inhaled steroid dose, 0.67; bronchodilator use, 0.58. Telephone interviews can provide repeatable and efficient measurements of health and patient-reported drug use in asthma.