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Biomedical subjects

P Farrington

Publications and source records attributed to P Farrington.

15 recordsLinked to original sources
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

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↗
PubMed2003

Does influenza vaccination increase consultations, corticosteroid prescriptions, or exacerbations in subjects with asthma or chronic obstructive pulmonary disease?

BACKGROUND: Concern over the safety of influenza vaccination in individuals with obstructive airways disease has contributed to suboptimal rates of vaccine uptake in this group. We investigated the safety of influenza vaccine in older people with asthma or chronic obstructive pulmonary disease (COPD) in a cohort from the UK General Practice Research Database (GPRD). METHODS: A population based cohort study of 12,000 individuals with asthma or COPD from 432 general practices was conducted. Incidence rate ratios (IRR) were calculated for asthma or COPD diagnoses, prescriptions for oral corticosteroids, and acute exacerbations on the day of vaccination and on days 1-2 and 3-14 after vaccination compared with other time periods in the influenza season. RESULTS: The IRRs for asthma or COPD diagnoses and oral corticosteroid prescriptions were increased on the day of vaccination (for example, the IRR for oral corticosteroid prescriptions for subjects with asthma during the 1992-3 influenza season was 8.24 (95% confidence interval 5.54 to 12.26)). However, there was no consistent increase in the IRR of any of the outcomes on days 1-2 or 3-14 after vaccination, and most of these IRRs were close to 1. Rates of exacerbation were low and showed no consistent statistically significant increase during any risk periods. CONCLUSIONS: Older people with asthma or COPD commonly have diagnoses recorded or prescriptions for oral corticosteroids given on the day of influenza vaccination, but there is no increased risk of adverse acute outcomes in the first 2 weeks after vaccination. Our findings strongly suggest that influenza vaccination is safe in this population.

Adrenal Cortex Hormones↗
PubMed2001

Does oral polio vaccine cause intussusception in infants? Evidence from a sequence of three self-controlled cases series studies in the United Kingdom.

BACKGROUND: The use of live oral poliomyelitis vaccine (OPV) has led to the elimination of poliomyelitis disease in many countries since licensure in 1960. The discovery of an increased risk of an intestinal obstruction known as intussusception following live rotavirus vaccination raised questions about the possibility of a link between live OPV and intussusception. METHODS: Three self-controlled case-series studies were carried out. The first was exploratory and included 218 intussusception episodes from hospital admissions data linked to vaccination records in the Thames region. The two subsequent studies, which used further hospital admissions data and the General Practice Research Database (GPRD) included 107 and 198 episodes respectively and were used to test hypotheses generated in the first study. RESULTS: In the exploratory study risk periods of up to 6 weeks after each dose were examined. The only period with some evidence of an increased risk was the 14-27-day period after the third dose (relative incidence (RI) = 1.97, p = 0.011). The second hospital admissions study and the GPRD study showed no evidence of an increased relative incidence in any putative risk period and did not confirm the increased risk in the 14-27-day period after dose 3 with a combined RI of 1.03. CONCLUSIONS: The sequence of studies does not support the hypothesis that OPV causes intussusception. The increased RI in the first study may be explained as a chance finding due to the number of risk periods examined and highlights the need for caution when looking at many risk periods without an a priori hypothesis.

Chi-Square Distribution↗
PubMed2000

The European Sero-Epidemiology Network: standardizing the enzyme immunoassay results for measles, mumps and rubella.

The ESEN (European Sero-Epidemiology Network) project was established to harmonize the seroepidemiology of five vaccine preventable infections including measles, mumps and rubella in eight European countries. This involved achieving comparability both in the assay results from testing in different centres and also sampling methodology. Standardization of enzyme immunoassay results was achieved through the development of common panels of sera by designated reference centres. The panels were tested at the reference laboratory and then distributed to each participating laboratory for testing using their routine methods. Standardization equations were calculated by regressing the quantitative results against those of the reference laboratory. Our study found large differences in unitage between participants, despite all using an EIA method standardized against an international or local standard. Moreover, our methodology adjusted for this difference. These standardization equations will be used to convert the results of main serosurvey testing into the reference country unitage to ensure inter-country comparability.

Antibodies, Viral↗
PubMed1998

Risk of hepatitis A infection in sewage workers.

OBJECTIVE: To evaluate the risk of hepatitis A virus (HAV) infection among sewage workers from occupational exposure to raw sewage. METHODS: An analytical cross sectional study of 241 company employees with possible occupational exposure to sewage in a large water and sewerage company was carried out. Previous exposure to hepatitis A virus infection was assessed, as were its associations with possible risk factors. RESULTS: Frequent occupational exposure to raw sewage was a significant risk factor for HAV infection, independently of other known risk factors (odds ratio 3.73, 95% confidence interval 1.48 to 9.37). Of 50 employees who reported occupational exposure to raw sewage most of the time, 30 (60%) had had HAV infection. CONCLUSION: Employees who are likely to be at risk of frequent exposure should have their immunity ensured. The salivary assay for IgG anti-HAV used in the study was highly specific and would be suitable for prevaccination testing of older employees, who are more likely to be immune.

Adult↗
PubMed1998

Safety assessment post-licensure.

The objectives of post-licensure surveillance are to identify rare or novel adverse events, estimate their rate of occurrence and distinguish those that are causally related to vaccination. Evidence of causality is based on biological plausibility supported by laboratory evidence of vaccine involvement and/or a statistically significant excess of events in the post-vaccination period. Passive reporting systems have methodological limitations, particularly for ascertaining reliable adverse event rates and investigating causal relationships. In Canada, an active surveillance system (IMPACT) has been established in sentinel paediatric hospitals where nurses scrutinise all admissions for conditions conforming to a defined set of adverse events. While ascertainment of events resulting in hospital admission should be complete, causality is difficult to assess without information on the incidence of such events outside the post-vaccination risk period. The use of computerised data bases which link clinical events with immunisation records have allowed the risk of events such as convulsions attributable to DTP, MMR and Hib vaccines to be defined. The record linkage method promises to be a useful method for routine surveillance of vaccine safety.

Adverse Drug Reaction Reporting Systems↗
PubMed1997

Changing patterns of case ascertainment and trends in meningococcal disease in England and Wales.

We have reviewed data on meningococcal disease routinely collected in England and Wales from 1989 to 1995 to illustrate and explain changing patterns and guide future surveillance. Statutory notifications of meningococcal meningitis and septicaemia, laboratory confirmed infections, and death registrations coded as meningococcal disease were analysed in terms of their numbers, the age of cases, season of the report, and (if available) site of isolation, serogroup, and serotype. Case fatality rates were estimated for clinically diagnosed and culture confirmed cases. The number of cases notified each year, in particular those notified as septicaemia, rose significantly over the period (p < 0.0001) but there was no net change in the number of culture confirmed cases. Case fatality rates estimated from routine data fell, most markedly for cases notified as septicaemia, but the true case fatality rate of culture confirmed cases did not change between 1993 and 1995. These data suggest that reporting practice changed between 1989 and 1995 and that the ascertainment of clinically diagnosed disease improved, particularly for meningococcal septicaemia. Late in 1995, reports from all data sources increased and the age distribution of both notified and laboratory confirmed cases changed. These changes were accompanied by an increase in the proportion of infections due to Neisseria meningitidis of serogroup C and a significant increase in serotype C2a infections (p < 0.0001). Continuing efforts to reconcile data from several sources will be needed to ensure that routine data can be interpreted accurately to provide evidence for the development of future vaccination policy and to monitor vaccination programmes. In addition, the role of non-culture diagnosis will be crucial in enhancing surveillance based on clinical diagnoses.

Adolescent↗
PubMed1997

An evaluation of nine commercial EIA kits for the detection of measles specific IgG.

Nine commercial EIAs for measles-specific IgG were compared with haemagglutination inhibition (HI) and plaque reduction neutralization (PRN). A total of 174 sera selected, to give approximately half of the sera without measles antibody by HI, were tested by all EIAs and HI. However, there was sufficient volume of only 101 samples for testing by PRN. A dilution curve of the British Standard measles antibody serum was also tested by each EIA. Assays were evaluated qualitatively against a consensus EIA result, HI and PRN: Gull, Melotest and Behring EIAs performed best. Quantitative evaluation was by assessment of the characteristics of the standard dilution curve, and by plotting differences with PRN against mean: Gull and Melotest EIAs were best.

Antibodies, Viral↗
PubMed1995

A new method for active surveillance of adverse events from diphtheria/tetanus/pertussis and measles/mumps/rubella vaccines.

We describe a new method for active post-marketing surveillance of vaccine safety based on patient records. We studied the association between diphtheria/tetanus/pertussis (DTP) vaccination and febrile convulsion, and between measles/mumps/rubella (MMR) vaccination and febrile convulsion and idiopathic thrombocytopenic purpura (ITP) in five district health authorities in England by linking vaccination records with computerised hospital admission records. We found an increased relative incidence for convulsions 0-3 days after DTP vaccination. The effect was limited to the third dose of vaccine for which the attributable risk (all ages) was 1 in 12,500 doses. Completion of vaccination by 4 months instead of 10 months after the change in the UK to an accelerated immunisation schedule may have resulted in a 4-fold decrease in febrile convulsions attributable to DTP vaccine. 67% of admissions for a convulsion 6-11 days after MMR vaccination were attributable to the measles component of the vaccine (risk 1 in 3000 doses). An excess of admissions for a convulsion 15-35 days after MMR vaccination was found only for vaccines containing the Urabe mumps strain (1 in 2600 Urabe doses). There was a causal association between MMR vaccination and ITP resulting in admission 15-35 days subsequently; there was no evidence of a mumps strain-specific effect. The estimated absolute risk of 1 in 24,000 doses was 5 times that calculated from cases passively reported by clinicians. This finding emphasises the need for active surveillance of adverse events. The record linkage method that we used is an effective way to identify vaccine-attributable adverse events.

Diphtheria-Tetanus-Pertussis Vaccine↗
PubMed1993

Risk of aseptic meningitis after measles, mumps, and rubella vaccine in UK children.

Cases of aseptic meningitis associated with measles/mumps/rubella vaccine were sought in thirteen UK health districts following a reported cluster in Nottingham which suggested a risk of 1 in 4000 doses, substantially higher than previous estimates based on cases reported by paediatricians (4 per million). Cases were ascertained by obtaining vaccination records of children with aseptic meningitis diagnosed from cerebrospinal fluid samples submitted to Public Health Laboratories or discharged from hospital with a diagnosis of viral meningitis. Both methods identified vaccination 15-35 days before onset as a significant risk factor and therefore indicative of a causal association. With both, half the aseptic meningitis cases identified in children aged 12-24 months were vaccine-associated with onset 15-35 days after vaccine. The study confirmed that the true risk was substantially higher than suggested by case reports from paediatricians, probably about 1 in 11,000 doses. However, the possibility that the aseptic meningitis induced by vaccination was largely asymptomatic and a chance laboratory finding in children investigated for other clinical conditions, particularly febrile convulsions, could not be excluded. Comparison of national reports of virus-positive mumps meningitis cases before and after the introduction of this vaccine indicated that the risk from wild mumps was about 4-fold higher than from vaccine. Altogether, 28 vaccine-associated cases were identified, all in recipients of vaccines containing the Urabe mumps strain. The absence of cases in recipients of vaccine containing the Jeryl Lynn strain, despite its 14% market share, suggested a higher risk from Urabe vaccine. A prospective adverse event surveillance system using the study methods is currently being established to assess the risk, if any, from the Jeryl Lynn strain which is now the only mumps vaccine used in the UK.

Child, Preschool↗