Martin Gulliford

Effects of prematurity and intrauterine growth on respiratory health and lung function in childhood.

OBJECTIVE--To determine whether birth weight and gestational age are associated with respiratory illness and lung function in children aged 5-11 years. DESIGN--Cross sectional analysis of parent reported birth weight, gestational age, and respiratory symptoms; parental smoking and social conditions; forced vital capacity (FVC), forced expiratory volume in one second (FEV1), forced expiratory rates between 25% and 75% and 75% and 85% (FEF25-75 and FEF75-85), and height. SETTING--Primary schools in England and Scotland in 1990. SUBJECTS--5573 children aged 5-11 (63.3% of eligible children) had respiratory symptoms analysed and 2036 children (67.1% of eligible children) had lung function measured. MAIN OUTCOME MEASURES--Symptoms of asthma, bronchitis, occasional and frequent wheeze, cough first thing in the morning, and cough at any other time and lung function. RESULTS--Birth weight adjusted for gestational age was significantly associated with all lung function measurements, except FEF25-75. The association remained for FVC (b = 0.475, 95% confidence interval 0.181 to 0.769) and FEV1 (b = 0.502, 0.204 to 0.800) after adjustment for gestational age, parental smoking, and social factors. FEF75-85 was the only lung function related to gestational age. Respiratory symptoms, especially wheeze most days (adjusted odds ratio 0.9, 0.84 to 0.97) were significantly associated with prematurity. Every extra week of gestation reduced the risk of severe wheeze by about 10%. CONCLUSIONS--Lung function is affected mainly by intrauterine environment while respiratory illness, especially wheezing, in childhood is related to prematurity.

Alarm symptoms in early diagnosis of cancer in primary care : cohort study using General Practice Research Database

Objective To evaluate the association between alarm symptoms and the subsequent diagnosis of cancer in a large population based study in primary care. Design Cohort study. Setting UK General Practice Research Database. Patients 762 325 patients aged 15 years and older, registered with 128 general practices between 1994 and 2000. First occurrences of haematuria, haemoptysis, dysphagia, and rectal bleeding were identified in patients with no previous cancer diagnosis.. Main outcome measure Positive predictive value of first occurrence of haematuria, haemoptysis, dysphagia, or rectal bleeding for diagnoses of neoplasms of the urinary tract, respiratory tract, oesophagus, or colon and rectum during three years after symptom onset. Likelihood ratio and sensitivity were also estimated. Results 11 108 first occurrences of haematuria were associated with 472 new diagnoses of urinary tract cancers in men and 162 in women, giving overall three year positive predictive values of 7.4% (95% confidence interval 6.8% to 8.1%) in men and 3.4% (2.9% to 4.0%) in women. After 4812 new episodes of haemoptysis, 220 diagnoses of respiratory tract cancer were made in men (positive predictive value 7.5%, 6.6% to 8.5%) and 81 in women (4.3%, 3.4% to 5.3%). After 5999 new diagnoses of dysphagia, 150 diagnoses of oesophageal cancer were made in men (positive predictive value 5.7%, 4.9% to 6.7%) and 81 in women (2.4%, 1.9 to 3.0%). After 15 289 episodes of rectal bleeding, 184 diagnoses of colorectal cancer were made in men (positive predictive value 2.4%, 2.1% to 2.8%) and 154 in women (2.0%, 1.7% to 2.3%). Predictive values increased with age and were strikingly high, for example, in men with haemoptysis aged 75-84 (17.1%, 13.5% to 21.1%) and in men with dysphagia aged 65-74 (9.0%, 6.8% to 11.7%). Conclusion New onset of alarm symptoms is associated with an increased likelihood of a diagnosis of cancer, especially in men and in people aged over 65. These data provide support for the early evaluation of alarm symptoms in an attempt to identify underlying cancers at an earlier and more amenable stage.

Self-monitoring in Type 2 diabetes mellitus: a meta-analysis

SUMMARY

Incidence of common compressive neuropathies in primary care

Apart from carpal tunnel syndrome, there are no population based studies of the epidemiology of compressive neuropathies. To provide this information, new presentations of compressive neuropathies among patients registered with 253 general practices in the UK General Practice Research Database with 1.83 million patient years at risk in 2000 were analysed. The study revealed that in 2000 the annual age standardised rates per 100 000 of new presentations in primary care were: carpal tunnel syndrome, men 87.8/women 192.8; Morton’s metatarsalgia, men 50.2/women 87.5; ulnar neuropathy, men 25.2/women 18.9; meralgia paraesthetica, men 10.7/women 13.2; and radial neuropathy, men 2.97/women 1.42. New presentations were most frequent at ages 55–64 years except for carpal tunnel syndrome, which was most frequent in women aged 45–54 years, and radial nerve palsy, which was most frequent in men aged 75–84 years. In 2000, operative treatment was undertaken for 31% of new presentations of carpal tunnel syndrome, 3% of Morton’s metatarsalgia, and 30% of ulnar neuropathy.

Pragmatic randomised trials using routine electronic health records: Putting them to the test

What to prescribe for a patient in general practice when the choice of treatments has a limited evidence base? Tjeerd-Pieter van Staa and colleagues argue that using electronic health records to enter patients into randomised trials of treatments in real time could provide the answer

Methods in health service research: Evaluation of health interventions at area and organisation level

This is the second of four articles Healthcare interventions are often implemented at the level of the organisation or geographical area rather than at the level of the individual patient or healthy subject. For example, screening programmes are delivered to residents of a particular area; health promotion interventions might be delivered to towns or schools; general practitioners deliver services to general practice populations; hospital specialists deliver health care to clinic populations. Interventions at area or organisation level are delivered to clusters of individuals. The evaluation of interventions based in an area or organisation may require the allocation of clusters of individuals to different intervention groups (see box 1).1 2 Cluster based evaluations present special problems both in design and analysis.3 Often only a small number of organisational units of large size are available for study, and the investigator needs to consider the most effective way of designing a study with this constraint. Outcomes may be evaluated either at cluster level or at individual level (table).4 Often cluster level interventions are aimed at modifying the outcomes of the individuals within clusters, and it will then be important to recognise that outcomes for individuals within the same organisation may tend to be more similar than for individuals in different organisational clusters (see box 2). This dependence between individuals in the same cluster has important implications for the design and analysis of organisation based studies.2 This paper addresses these issues. #### Summary points Health interventions are often implemented at the levels of health service organisational unit or of geographical or administrative area The unit of intervention is then a cluster of individual patients or healthy subject Evaluation of cluster level interventions may be difficult because only a few units of large size may be available for study, evaluation may be at …

Disturbed sleep: effects of sociocultural factors and illness

To assess the prevalence of sleep disturbance and associated risk factors, sleep patterns were analysed in 14 372 English and Scottish children. Approximately 4% of children aged 5 experienced disturbed sleep more than once a week, but this decreased to 1% from age 9. Less than 25% of the parents with an affected child consulted a doctor. Sleep disturbance was associated with persistent wheezing compared to non-wheezing children (odds ratio 4.42; 95% confidence interval (CI) 3.17 to 6.13), and more frequent in children of Indian subcontinent descent than in white children (odds ratio 2.20; 95% CI 1.34 to 3.60), and in children whose mother reached no more than primary education compared with those with higher education (odds ratio 2.41; 95% CI 1.51 to 3.84). Sociocultural factors associated with ethnicity and respiratory illness are important risk factors for sleeping disorders in childhood.

Headache and migraine in primary care: consultation, prescription, and referral rates in a large population

Background/Aims: Headache is the most common new neurological symptom seen by general practitioners and neurologists. This study describes headache consultation, prescription, and referral rates in a large sample of UK general practices. Methods: Analysis of data from patients ⩾15 years registered at 253 UK general practices diagnosed with headache/migraine from 1992 to 2000. Rates were age standardised using the European standard population for reference. Results: There were 13.2 million patient years of observation. Headache consultation rates were 6.4/100 patients/year in women and 2.5 in men. They were highest at 15–24 years (15.8/100 in women; 5.8/100 in men), decreasing with age. Antimigraine drugs were prescribed at 36.7% of consultations for women and 26.6% for men. Among referrals to specialists, 55% were to neurology and 30% to general medicine. The neurology referral rate in patients with headache was 2.1/100, and was higher in men (2.7/100) than women (1.9/100). Conclusions: These results provide precise age specific and age standardised estimates for headache consulting in general practice, in addition to prescribing and referral to specialist care. Consultation rates are highest in young women; hospital referrals peak in middle aged men. Research is needed into reasons for referral, and on better ways of delivering headache services.

Incidence, Mortality, and Disease Associations of Pyoderma Gangrenosum in the United Kingdom: A Retrospective Cohort Study

Pyoderma gangrenosum (PG) is an important disease with significant complications. The objectives of this study were to determine incidence and mortality of PG and strength of reported associations. A retrospective cohort study was completed using computerized medical records from the General Practice Research Database, a large representative UK database. Patients with PG and three groups of age-, sex-, and practice-matched controls--general population, rheumatoid arthritis (RA), and inflammatory bowel disease (IBD) controls--were included in the study. Incidence and mortality were determined and validation undertaken to inform diagnostic accuracy. In all there were 313 people with the median age of 59 (interquartile range 41-72) years, and of them 185 (59%) were female. The adjusted incidence rate standardized to European standard population was 0.63 (95% confidence interval (CI) 0.57-0.71) per 100,000 person-years. The risk of death was three times higher than that for general controls (adjusted hazard ratio=3.03, 95% CI 1.84-4.73, P<0.001), 72% higher than that for IBD controls (adjusted hazard ratio=1.72, 95% CI 1.17-2.59, P=0.013), with a borderline increase compared with RA controls (adjusted hazard ratio=1.55, 95% CI 1.01-2.37, P=0.045). Disease associations were present in 110 (33%) participants: IBD, n=67 (20.2%); RA, n=39 (11.8%); and hematological disorders, n=13 (3.9%). To our knowledge, there are no previous population-based studies of the epidemiology of PG, an important disease with significantly increased mortality.

The opportunities and challenges of pragmatic point-of-care randomised trials using routinely collected electronic records: Evaluations of two exemplar trials

BACKGROUND Pragmatic trials compare the effects of different decisions in usual clinical practice. OBJECTIVES To develop and evaluate methods to implement simple pragmatic trials using routinely collected electronic health records (EHRs) and recruiting patients at the point of care; to identify the barriers and facilitators for general practitioners (GPs) and patients and the experiences of trial participants. DESIGN Two exemplar randomised trials (Retropro and eLung) with qualitative evaluations. SETTING Four hundred and fifty-nine English and Scottish general practices contributing EHRs to a research database, of which 17 participated in the trials. PARTICIPANTS Retropro aimed to recruit 300 patients with hypercholesterolaemia and high cardiovascular risk and eLung aimed to recruit 150 patients with a chronic obstructive pulmonary disease exacerbation. INTERVENTIONS Retropro randomised between simvastatin and atorvastatin and eLung between immediate antibiotics and deferred or non-use. eLung recruited during an unscheduled consultation using EHR flagging. MAIN OUTCOME MEASURE Successful trial completion with implementation of information technology (IT) system for flagging and data processing and documentation of operational and scientific experiences. DATA SOURCES EHR research database. RESULTS The governance approval process took over 3 years. A total of 58.8% of the practices (n = 270) expressed interest in participating. The number of interested practices dropped substantially with each stage of the governance process. In Retropro, 6.5% of the practices (n = 30) were eventually approved and 3.7% (n = 17) recruited patients; in eLung, these numbers were 6.8% (n = 31) and 1.3% (n = 6) respectively. Retropro successfully completed recruitment (301 patients) whereas eLung recruited 31 patients. Retropro recruited 20.6% of all statin starters in recruiting practices and 1.1% in the EHR database; the comparable numbers for eLung were 32.3% and 0.9% respectively. The IT system allowed for complex eligibility criteria with central on and off control of recruitment and flagging at a practice. Good Clinical Practice guidelines, governance and consent procedures were found to have substantially affected the intended simple nature of the trials. One qualitative study of 13 clinicians found that clinicians were generally positive about the principle of computerised trial recruitment (flagging during consultation). However, trials which did not include patients with acute illness were favoured. The second qualitative process evaluation interviewed 27 GPs about their actual experiences, including declining, recruiting and non-recruiting GPs. Opportunistic patient recruitment during a routine GP consultation was found to be the most controversial element. The actual experiences of recruiting patients during unscheduled consultation were generally more positive than the hypothetical views of GPs. Several of the recruiting GPs reported the process took 5 minutes and was straightforward and feasible on most occasions. Almost all GPs expressed their strong support for the use of EHRs for trials. Ten eLung participants were interviewed, all of whom considered it acceptable to be recruited during a consultation and to use EHRs for trials. CONCLUSIONS EHR point-of-care trials are feasible, although the recruitment of clinicians is a major challenge owing to the complexity of trial approvals. These trials will provide substantial evidence on clinical effectiveness only if trial interventions and participating clinicians and patients are typical of usual clinical care and trials are simple to initiate and conduct. Recommendations for research include the development of evidence and implementation of risk proportionality in trial governance and conduct. TRIAL REGISTRATION Current Controlled Trials ISRCTN33113202 and ISRCTN72035428. FUNDING This project was funded by the NIHR Health Technology Assessment programme and the Wellcome Trust and will be published in full in Health Technology Assessment; Vol. 18, No. 43. See the NIHR Journals Library website for further project information.