PubMed Health⌕ Search

Biomedical subjects

R Hubbard

Publications and source records attributed to R Hubbard.

At least 19 recordsLinked to original sources
PubMed2006

Hormone replacement therapy and cataract: a population-based case-control study.

PURPOSE: Laboratory studies have suggested that hormone replacement therapy (HRT) may protect against the development of cataract, but epidemiological studies in humans have thus far been inconclusive. The aim of this study was to assess the association between hormone replacement therapy and cataract. METHODS: Population-based case-control study using data from the General Practice Research Database in the UK. Participants were 10 000 women aged 45 years and over with diagnosed cataract and 10 000 controls matched on age, general practice, and calendar period. RESULTS: The crude odds ratio for the association between cataract and ever-use of oestrogen-only hormone replacement therapy was 1.13 (95% CI 0.99-1.29). This reduced to 0.81 (95% CI 0.71-0.94) after adjustment for consultation rate. Similarly, the crude odds ratio for the association between cataract and ever-use of a formulation containing oestrogen and progestogen was 1.18 (95% CI 1.01-1.39), reducing to 0.86 (95% CI 0.72-1.02) after adjustment for consultation rate. CONCLUSIONS: Oestrogen-only and oestrogen-progestogen hormone replacement therapies are associated with a small reduced risk of cataract. This data adds to the growing body of evidence on the effects of HRT on health. All potential benefits and risks of this therapy should be taken into account when considering its use.

Aged↗
PubMed2006

Is an internal comparison better than using national data when estimating mortality in longitudinal studies?

BACKGROUND: Discrepancies between the results of different studies looking at mortality in similar disease cohorts led us to consider the impact of methodology upon outcome. METHODS: Cohort studies were carried out using age, sex, practice, and calendar time matched control groups in the general practice research database. Data were used on all subjects with inflammatory bowel disease, coeliac disease, or Barrett's oesophagus. Mortality data for the population of England and Wales were obtained from the UK Office for National Statistics. The study compared hazard ratios (HR) for mortality using the matched controls to those found when an indirect standardisation to the mortality experience of England and Wales was carried out. RESULTS: For all three conditions the mortality risk was slightly lower when the national population data were used compared with the internal comparison group (coeliac disease HR 1.33 v standardised mortality ratios (SMR) 1.25, Barrett's oesophagus HR 1.32 v SMR 1.32, inflammatory bowel disease HR 1.50 v SMR 1.34). CONCLUSIONS: A bias was found towards underestimating mortality risk when cohort studies use national population death rates as a comparator. Estimates obtained when an internal comparison group has been used are probably more appropriate.

Adult↗
PubMed2006

Towards predictive ligand design with free-energy based computational methods?

The accurate prediction of ligand-biopolymer binding affinities is of general interest to medicinal chemistry, as well as to the broader field of molecular recognition. The ability to predict computationally the thermodynamics of these molecular recognition processes has been relatively weak until recently, however, continued developments on several fronts are extending the scope of applicability of these methods. The rapid growth in the number of protein-ligand structures has initially led to the development of a range of empirical scoring functions based on relatively simple descriptions of intermolecular interactions. These methods have had some success in ranking binding affinities when tuned to particular protein systems or in rather qualitative estimates of molecular fit in fast docking calculations. However, they are too unreliable for more detailed, quantitative, assessment and comparison of binding affinities. Physics-based free energy calculations are in principle more general and have the potential to be significantly more accurate. These approaches have seen steady development over many years and rely on carefully calibrated molecular energy functions (force-fields), simulations of the systems with explicit solvent, and the coming-of-age of continuum solvation models. In addition to the initially developped Free Energy Perturbation (FEP) and Thermodynamic Integration (TI) methods, new approaches include the Molecular Mechanics-Poisson-Boltzmann Surface Area (MM-PBSA) and the Linear Interaction Energy (LIE) approaches. This review concentrates on MM-PBSA and LIE, and their variants. The routine application of these calculations is becoming possible because of enhanced computational hardware and the development of a range of computational chemistry tools. This review addresses: i) the basic principles behind free energy calculations ii) recent methodological advances iii) comparisons of predicted and experimentally determined affinities iv) the uncertainties and limitations of both the computational and experimental data v) areas where progress can be made vi) the practicality of applying the methods at the different stages of the drug discovery and optimization process.

Animals↗
PubMed2005

Bupropion and the risk of sudden death: a self-controlled case-series analysis using The Health Improvement Network.

BACKGROUND: Bupropion is an effective smoking cessation therapy but its use in the UK has been limited by concerns that it may increase the risk of sudden death. METHODS: Data for all patients prescribed bupropion within The Health Improvement Network (a computerised general practice database) were extracted and the self-controlled case-series method was used to estimate the relative incidence of death during the first 28 days of treatment. The incidence of seizures, a recognised adverse effect of bupropion, was also investigated during this period. RESULTS: A total of 9329 individuals had been prescribed bupropion (mean age 44 years, 48% male). The total person-time after the first prescription for bupropion was 17,586 years, and during this time 121 people died. Two people died within the first 28 days of treatment, which was less than expected in comparison with the remaining observation period by an incidence ratio of 0.50 (95% confidence interval (CI) 0.12 to 2.05). Twenty eight people were recorded as having a total of 45 seizures (23 before starting bupropion, two in the first 28 days of treatment, and 20 at a later point). The relative incidence of seizures during the first 28 days of treatment was 3.62 (95% CI 0.87 to 15.09), equivalent to one additional seizure per 6219 first time bupropion users. CONCLUSIONS: Bupropion use is probably associated with an increased risk of seizures, but no evidence was found to suggest that the drug is associated with an increased risk of sudden death.

Antidepressive Agents, Second-Generation↗
PubMed2005

Validation of the International Study of Asthma and Allergies in Children (ISAAC) and U.K. criteria for atopic eczema in Ethiopian children.

BACKGROUND: Reliable diagnostic criteria for atopic eczema (AE) are essential in order to make international comparisons and to identify possible disease risk factors. Little is known about the prevalence of atopic eczema and validity of diagnostic criteria for AE in developing countries where English is not the first language. OBJECTIVES: We sought to determine the prevalence of AE in an area of urban and rural Ethiopia, and to compare the predictive values of different questionnaire and examination methods for diagnosing AE in this population. METHODS: We conducted a cross-sectional survey of 7915 children aged 1-5 years living in and around the town of Jimma in southwest Ethiopia. AE prevalence was assessed in two ways: (i) by using the International Study for Asthma and Allergies in Childhood (ISAAC) questionnaire, and (ii) using the U.K. refinement of Hanifin and Rajka's diagnostic criteria. All possible cases identified by screening questions and random samples of controls were then examined by an experienced local paediatrician, who acted as a reference standard to determine the predictive value of the criteria used to diagnose AE. RESULTS: The overall 1-year period prevalence of AE according to ISAAC and U.K. criteria was 4.4%[95% confidence interval (CI) 3.95-4.85] and 1.8% (95% CI 1.5-2.1), respectively. Corresponding point prevalence estimates (symptoms in the last week) were 1.8% for ISAAC and 1.3% for the U.K. criteria. The positive predictive values of the ISAAC and U.K. criteria questions for AE symptoms still reported to be present (in the last week) at the doctor's examination were 48.8% and 55.5%, respectively. Corresponding negative predictive values were 90.5% and 90.1%, respectively. The sign of visible flexural dermatitis (a component of the U.K. criteria) when used alone had positive and negative predictive values of 57% and 91%, respectively. CONCLUSIONS: Neither the ISAAC nor U.K. criteria performed especially well in predicting cases of AE in this survey. Possible reasons include problems with questionnaire translation, cultural conceptions of terminology, asking parents rather than the child about symptoms, the transient nature of AE signs, and differences in what a doctor perceives to constitute a typical case of AE. The results do not preclude the use of standardized diagnostic criteria alongside a doctor's examination in future surveys of Ethiopian children, and knowledge of the criteria's limited predictive value should help to interpret study findings that have employed such criteria. Consideration should be given to adopting the sign of visible flexural dermatitis as a standard for estimating the point prevalence of AE throughout the world because it is less susceptible to problems with translation and interpretation.

Age Distribution↗
PubMed2005

A case control study of age related macular degeneration and use of statins.

AIMS: Age related macular degeneration (AMD) is the leading cause of blindness in industrialised countries. Previous studies have suggested that statins may have a protective effect against the disease; however, existing studies have had limited power to reliably detect or exclude an effect and have produced conflicting results. The authors assessed the risk of AMD associated with the use of statins. METHODS: Population based case control study using the United Kingdom General Practice Research Database. 18 007 people with diagnosed AMD were compared with 86 169 controls matched on age, sex, and general practice. The primary outcome was the odds ratio for the association between exposure to statins and AMD. RESULTS: The crude odds ratio for the association between any recorded exposure to statins and AMD was 1.32 (95% CI 1.17 to 1.48), but this reduced to 0.93 (95% CI 0.81 to 1.07, p=0.33) after adjustment for consultation rate, smoking, alcohol intake, body mass index, atherosclerotic disease, hyperlipidaemia, heart failure, diabetes mellitus, hypertension, use of other cardiovascular drugs, and use of fibrates. There was no evidence that the risk varied by dose of statin, duration of use, or that the risk varied for individual statins. CONCLUSION: In the short and medium term statin use is not associated with a decreased risk of AMD. Whether subgroups of patients with specific forms of AMD (particularly choroidal neovascularisation) benefit from statin therapy remains a possibility.

Aged↗
PubMed2005

General population based study of the impact of tricyclic and selective serotonin reuptake inhibitor antidepressants on the risk of acute myocardial infarction.

OBJECTIVE: To investigate the impact of tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) on the risk of first acute myocardial infarction (MI). DESIGN: Case-control analysis and a self controlled case series. SETTING: 644 general practices throughout England, Scotland, Wales, and Northern Ireland. PATIENTS: Over 60,000 cases of MI and 360,000 age, sex, and practice matched controls randomly selected from the UK General Practice Research Database. MAIN OUTCOME MEASURES: Matched odds ratios and incidence rate ratios estimating whether there is an acute or prolonged increased risk of MI after exposure to TCA and SSRI drugs and individual drugs within these families. RESULTS: Case-control analysis found an initial increased risk of MI after TCA exposure (for example, at 1-7 days after the first dothiepin prescription: odds ratio (OR) 1.90, 95% confidence interval (CI) 1.15 to 3.14) or SSRI exposure (for example, at 1-7 days after first fluoxetine prescription: OR 2.59, 95% CI 1.44 to 4.66). In the self controlled analysis the equivalent risk estimates were an incidence rate ratio of 1.43, 95% CI 0.92 to 2.22 for dothiepin and an incidence rate ratio of 1.66, 95% CI 1.01 to 2.71 for fluoxetine. CONCLUSIONS: Antidepressant prescriptions are associated with an increased risk of MI. The size of these effects is similar for TCA and SSRI exposures; however, the lack of specificity between types of antidepressants and the lower risks found in the self controlled analysis suggest that these associations are more likely due to factors relating to underlying depression and health services utilisation than to specific adverse drug effects.

Adult↗
PubMed2005

Use of nicotine replacement therapy and the risk of acute myocardial infarction, stroke, and death.

OBJECTIVE: To determine whether nicotine replacement therapy (NRT) is associated with an increased risk of acute myocardial infarction, acute stroke, or death. DESIGN: Self control case series analysis of data from The Health Improvement Network (THIN) to estimate the relative incidence of myocardial infarction and stroke in four 14 day periods before and after the first prescription for NRT. SETTING: THIN is a computerised general practice database. SUBJECTS: Patients contributing data to THIN. INTERVENTIONS: Observational study of NRT. MAIN OUTCOMES: Acute myocardial infarction, acute stroke, and death. RESULTS: 33,247 individuals had been prescribed NRT, of whom 861 had had a myocardial infarction and 506 a stroke. There was a progressive increase in the incidence of first myocardial infarction in the 56 days leading up to the first NRT prescription (overall incidence ratio 5.55, 95% confidence interval (CI) 4.42 to 6.98), but the incidence fell after this time and was not increased in the 56 days after starting NRT (incidence ratio 1.27, 95% CI 0.82 to 1.97). The results were similar for second myocardial infarction and stroke, and for subgroups of people with pre-existing angina and hypertension. There were 960 deaths in our cohort during a mean follow up period of 2.6 years after starting NRT, with no evidence of an increased mortality in the 56 days after the NRT prescription (incidence ratio 0.86, 95% CI 0.60 to 1.23). CONCLUSIONS: The use of NRT is not associated with any increase in the risk of myocardial infarction, stroke, or death.

Adult↗
PubMed2004

Risk of vascular disease in adults with diagnosed coeliac disease: a population-based study.

BACKGROUND: It has been suggested that vascular disease mortality may be reduced in coeliac disease because of lower levels of blood pressure, cholesterol and body mass. AIM: To examine whether people with coeliac disease are at reduced risk of various vascular diseases. METHODS: We identified 3,790 adults with diagnosed coeliac disease and 17,925 age- and sex-matched controls in the General Practice Research Database. We estimated odds ratios for diagnosed hypertension, hypercholesterolaemia and atrial fibrillation and hazard ratios for myocardial infarction and stroke. RESULTS: Adults with coeliac disease, compared with controls, were less likely to have had a diagnosis of hypertension [11% vs. 15%, odds ratio 0.68 (95% confidence interval: 0.60-0.76)] or hypercholesterolaemia [3.0% vs. 4.8%, odds ration 0.58 (95% confidence interval: 0.47-0.72)] but slightly more likely to have had atrial fibrillation [2.1% vs. 1.7%, odds ratio 1.26 (95% confidence interval: 0.97-1.64)]. The hazard ratio for myocardial infarction was 0.85 (95% confidence interval: 0.63-1.13), while the hazard ratio for stroke was 1.29 (95% confidence interval: 0.98-1.70). CONCLUSIONS: Although rates of myocardial infarction and stroke were not substantially different, adults with coeliac disease do have a lower prevalence of hypertension and hypercholesterolaemia compared with the general population. The effect of a gluten-free diet on cardiovascular risk factors should be determined before any screening programmes for coeliac disease are instituted.

Adult↗
PubMed2004

Risk factors in carpal tunnel syndrome.

We have undertaken a large case-control study using the UK General Practice Research Database to quantify the relative contributions of the common risk factors for carpal tunnel syndrome (CTS) in the community. Cases were patients with a diagnosis of CTS and, for each, four controls were individually matched by age, sex and general practice. Our dataset included 3,391 cases, of which 2,444 (72%) were women, with a mean age at diagnosis of 46 (range 16-96) years. Multivariate analysis showed that the risk factors associated with CTS were previous wrist fracture (OR=2.29), rheumatoid arthritis (OR=2.23), osteoarthritis of the wrist and carpus (OR=1.89), obesity (OR=2.06), diabetes (OR=1.51), and the use of insulin (OR=1.52), sulphonylureas (OR=1.45), metformin (OR=1.20) and thyroxine (OR=1.36). Smoking, hormone replacement therapy, the combined oral contraceptive pill and oral corticosteroids were not associated with CTS. The results were similar when cases were restricted to those who had undergone carpal tunnel decompression.

Adolescent↗
PubMed2004

Dupuytren's disease risk factors.

Dupuytren's is a common problem, but little is known about its aetiology. We have undertaken a large case-control study to assess and quantify the relative contributions of diabetes and epilepsy as risk factors for Dupuytren's in the community. Cases were patients with a diagnosis of Dupuytren's disease and, for each, two controls were individually matched by age, sex, and general practice. Our dataset included 821 cases and 1,642 controls. Five hundred and eighty-eight (72%) of the cases were men. The mean age at diagnosis was 62 (range 24-97) years. Diabetes was a significant risk factor for Dupuytren's disease (OR=1.75) and there was an increased risk for medicinally treated diabetes (metformin--OR=3.56; sulphonylureas--OR=1.75) and particularly insulin controlled (OR=4.38) rather than diet-controlled diabetes. Epilepsy (OR=1.12) and anti-epileptic medications were not associated with Dupuytren's disease. Ascertainment bias in previous studies may explain the reported association with epilepsy.

Adult↗
PubMed2004

Domestic risk factors for wheeze in urban and rural Ethiopian children.

BACKGROUND: To identify which environmental exposures underpin the emergence of asthma epidemics, we need to study epidemics as they appear, as is now happening in the Jimma region of Ethiopia. We have previously studied risk factors for asthma in adults in Jimma and have now completed a survey of young children. AIM: To establish the prevalence of asthma in urban and rural children in Jimma, and to identify locally important risk factors. DESIGN: Cross-sectional survey. METHODS: All children aged 1-5 years living in Jimma town and three surrounding rural regions were identified. Data were collected using an interviewer-led questionnaire, and consenting children had skin prick tests to house dust mite and cockroach. RESULTS: We surveyed 7155 children, of whom 3623 (51%) were female and 4285 (60%) lived in the urban area. The prevalence of wheeze in the last year was 3.4%, and was lower in the rural area (OR 0.47; 95%CI 0.34-0.66). In the urban area, the main risk factors for wheeze were a longer duration of breastfeeding, use of kerosene, and environmental tobacco smoke, while living with animals was protective. In rural children, the main risk factors were a positive skin prick test and living with animals. DISCUSSION: The prevalence of wheeze in children in the Jimma region is low, particularly in rural children. In addition to having an impact on disease prevalence, place of residence also appears to modify the impact of environmental risk factors for wheeze.

Animals↗
PubMed2004

Hip fractures in patients with inflammatory bowel disease and their relationship to corticosteroid use: a population based cohort study.

BACKGROUND: Inflammatory bowel disease (IBD) is known to be associated with reduced bone density but the extent to which this results in an increased risk of fracture and the contribution of corticosteroid therapy are unclear. We have conducted a large cohort study to address these issues. METHODS: We selected subjects within the General Practice Research Database (GPRD) with a diagnosis of IBD and up to five matched controls for each patient. We derived dates of recorded hip fractures and also information on smoking, use of corticosteroids, and a number of other drugs. We calculated the absolute risk of fracture and the relative risk as a hazard ratio corrected for available confounders by Cox regression. RESULTS: Seventy two hip fractures were recorded in 16 550 IBD cases and 223 in 82 917 controls. Cox modelling gave an unadjusted relative risk of hip fracture of 1.62 (95% confidence interval (CI) 1.24-2.11) for all IBD, 1.49 (1.04-2.15) for ulcerative colitis (UC) and 2.08 (1.36-3.18) for Crohn's disease (CD). Multivariate modelling showed that both current and cumulative use of corticosteroids and use of opioid analgesics confounded this relationship. After adjusting for confounding, the relative risk was 1.41 (0.94-2.11) for UC and 1.68 (1.01-2.78) for CD. CONCLUSION: The risk of hip fracture is increased approximately 60% in IBD patients. Corticosteroid use is a contributor to this, both in the long term as previously recognised and also in an acute reversible manner. The majority of hip fracture risk in IBD patients however cannot be attributed to steroid use.

Adult↗
PubMed2003

Cataract and the use of statins: a case-control study.

BACKGROUND: In animal studies, statins have induced cataract formation. Because incident cataract is relatively uncommon, studies in humans have been unable to exclude a clinically important effect. AIMS: To assess the risk of cataract associated with the use of statins, and whether it is increased by concurrent use of drugs that inhibit the cytochrome P450 system. DESIGN: Population-based case-control study. METHODS: Patients were randomly sampled from the UK General Practice Research Database. The study included 15,479 people with cataract and 15,479 controls matched for age, sex, practice and observation period. RESULTS: The crude odds ratio (OR) for the association between any recorded exposure to statins and cataract was 1.41 (95%CI 1.21-1.65), but this reduced to 1.04 (95%CI 0.89-1.23, p=0.6) after adjustment for consultation rate. There was no evidence that the risk increased with higher doses or longer duration of statin use, or that the risk varied by individual statin. There was no evidence that the risk of cataract was increased by concurrent use of statins and drugs that inhibit the cytochrome P450 system. DISCUSSION: In the short- and medium-term, statins do not seem to be associated with an increased risk of cataract. The need to assess the effects of long-term statin exposure on the eye remains.

Aged↗