Sara L Thomas

Validation and validity of diagnoses in the General Practice Research Database: a systematic review

AIMS To investigate the range of methods used to validate diagnoses in the General Practice Research Database (GPRD), to summarize findings and to assess the quality of these validations. METHODS A systematic literature review was performed by searching PubMed and Embase for publications using GPRD data published between 1987 and April 2008. Additional publications were identified from conference proceedings, back issues of relevant journals, bibliographies of retrieved publications and relevant websites. Publications that reported attempts to validate disease diagnoses recorded in the GPRD were included. RESULTS We identified 212 publications, often validating more than one diagnosis. In total, 357 validations investigating 183 different diagnoses met our inclusion criteria. Of these, 303 (85%) utilized data from outside the GPRD to validate diagnoses. The remainder utilized only data recorded in the database. The median proportion of cases with a confirmed diagnosis was 89% (range 24–100%). Details of validation methods and results were often incomplete. CONCLUSIONS A number of methods have been used to assess validity. Overall, estimates of validity were high. However, the quality of reporting of the validations was often inadequate to permit a clear interpretation. Not all methods provided a quantitative estimate of validity and most methods considered only the positive predictive value of a set of diagnostic codes in a highly selected group of cases. We make recommendations for methodology and reporting to strengthen further the use of the GPRD in research.

What does epidemiology tell us about risk factors for herpes zoster

Reactivation of latent varicella zoster virus as herpes zoster is thought to result from waning of specific cell-mediated immunity, but little is known about its determinants in individuals with no underlying immunosuppression. We systematically reviewed studies of zoster epidemiology in adults and analysed data from a large morbidity study to identify factors that might be modulated to reduce the risk of zoster. Annual zoster incidence in population-based studies varied from 3.6-14.2/10(3) in the oldest individuals. Risk factors identified in analytical studies that could explain this variation included age, sex, ethnicity, genetic susceptibility, exogenous boosting of immunity from varicella contacts, underlying cell-mediated immune disorders, mechanical trauma, psychological stress, and immunotoxin exposure. Our review highlights the lack of information about risk factors for zoster. We suggest areas of research that could lead to interventions to limit the incidence of zoster. Such research might also help to identify risk factors for age-related immune decline.

Male circumcision and risk of syphilis, chancroid, and genital herpes: a systematic review and meta-analysis.

Objectives: Male circumcision is associated with reduced risk of HIV infection. This may be partly because of a protective effect of circumcision on other sexually transmitted infections (STI), especially those causing genital ulcers, but evidence for such protection is unclear. Our objective was to conduct a systematic review and meta-analyses of the associations between male circumcision and infection with herpes simplex virus type 2 (HSV-2), Treponema pallidum, or Haemophilus ducreyi. Methods: Electronic databases (1950–2004) were searched using keywords and text terms for herpes simplex, syphilis, chancroid, ulcerative sexually transmitted diseases, or their causative agents, in conjunction with terms to identify epidemiological studies. References of key articles were hand searched, and data were extracted using standardised forms. Random effects models were used to summarise relative risk (RR) where appropriate. Results: 26 articles met the inclusion criteria. Most syphilis studies reported a substantially reduced risk among circumcised men (summary RR = 0.67, 95% confidence interval (CI) 0.54 to 0.83), although there was significant between study heterogeneity (p = 0.01). The reduced risk of HSV-2 infection was of borderline statistical significance (summary RR = 0.88, 95% CI 0.77 to 1.01). Circumcised men were at lower risk of chancroid in six of seven studies (individual study RRs: 0.12 to 1.11). Conclusions: This first systematic review of male circumcision and ulcerative STI strongly indicates that circumcised men are at lower risk of chancroid and syphilis. There is less association with HSV-2. Potential male circumcision interventions to reduce HIV in high risk populations may provide additional benefit by protecting against other STI.

Risk of deep vein thrombosis and pulmonary embolism after acute infection in a community setting

BACKGROUND Acute infection increases the risk of arterial cardiovascular events, but effects on venous thromboembolic disease are less well established. Our aim was to investigate whether acute infections transiently increase the risk of venous thromboembolism. METHODS We used the self-controlled case-series method to study the risk of first deep vein thrombosis (DVT) (n=7278) and first pulmonary embolism (PE) (n=3755) after acute respiratory and urinary tract infections. Data were obtained from records from general practices who had registered patients with the UKs Health Improvement Network database between 1987 and 2004. FINDINGS The risks of DVT and PE were significantly raised, and were highest in the first two weeks, after urinary tract infection. The incidence ratio for DVT was 2.10 (95% CI 1.56-2.82), and that for PE 2.11 (1.38-3.23). The risk gradually fell over the subsequent months, returning to the baseline value after 1 year. The risk of DVT was also higher after respiratory tract infection, but possible diagnostic misclassification precluded a reliable estimate of the risk of PE after respiratory infection. INTERPRETATION Acute infections are associated with a transient increased risk of venous thromboembolic events in a community setting. Our results confirm that infection should be added to the list of precipitants for venous thromboembolism, and suggest a causal relation.

Contacts with varicella or with children and protection against herpes zoster in adults: a case-control study

BACKGROUND Whether exogenous exposure to varicella-zoster-virus protects individuals with latent varicella-zoster virus infection against herpes zoster by boosting immunity is not known. To test the hypothesis that contacts with children increase exposure to varicella-zoster virus and protect latently infected adults against zoster, we did a case-control study in south London, UK. METHODS From 22 general practices, we identified patients with recently diagnosed zoster, and control individuals with no history of zoster, matched to patients by age, sex, and practice. Participants were asked about contacts with people with varicella or zoster in the past 10 years, and social and occupational contacts with children as proxies for varicella contacts. Odds ratios were estimated with conditional logistic regression. FINDINGS Data from 244 patients and 485 controls were analysed. On multivariable analysis, protection associated with contacts with a few children in the household or via childcare seemed to be largely mediated by increased access to children outside the household. Social contacts with many children outside the household and occupational contacts with ill children were associated with graded protection against zoster, with less than a fifth the risk in the most heavily exposed groups compared with the least exposed. The strength of protection diminished after controlling for known varicella contacts; the latter remained significantly protective (odds ratio 0.29 [95% CI 0.10-0.84] for those with five contacts or more). INTERPRETATION Re-exposure to varicella-zoster virus via contact with children seems to protect latently infected individuals against zoster. Reduction of childhood varicella by vaccination might lead to increased incidence of adult zoster. Vaccination of the elderly (if effective) should be considered in countries with childhood varicella vaccination programmes.

Isoniazid Preventive Therapy and Risk for Resistant Tuberculosis

Preventive therapy may increase risk for drug resistance.

Herpes Zoster Vaccine Effectiveness against Incident Herpes Zoster and Post-herpetic Neuralgia in an Older US Population: A Cohort Study

Sinead Marie Langan and colleagues studied a cohort of more than 750,000 individuals over the age of 65 years to assess whether herpes zoster vaccine is effective against incident zoster and post-herpetic neuralgia in an older population.

Changes in the incidence, prevalence and mortality of bronchiectasis in the UK from 2004 to 2013: a population based cohort study

There is a paucity of data on incidence, prevalence and mortality associated with non-cystic fibrosis bronchiectasis. Using the Clinical Practice Research Datalink for participants registered between January 1, 2004 and December 31, 2013, we determined incidence, prevalence and mortality associated with bronchiectasis in the UK and investigated changes over time. The incidence and point prevalence of bronchiectasis increased yearly during the study period. Across all age groups, the incidence in women increased from 21.2 per 100 000 person-years in 2004 to 35.2 per 100 000 person-years in 2013 and in men from 18.2 per 100 000 person-years in 2004 to 26.9 per 100 000 person-years in 2013. The point prevalence in women increased from 350.5 per 100 000 in 2004 to 566.1 per 100 000 in 2013 and in men from 301.2 per 100 000 in 2004 to 485.5 per 100 000 in 2013. Comparing morality rates in women and men with bronchiectasis in England and Wales (n=11 862) with mortality rates in the general population from Office of National Statistics data showed that in women the age-adjusted mortality rate for the bronchiectasis population was 1437.7 per 100 000 and for the general population 635.9 per 100 000 (comparative mortality figure of 2.26). In men, the age-adjusted mortality rate for the bronchiectasis population was 1914.6 per 100 000 and for the general population 895.2 per 100 000 (comparative mortality figure of 2.14). Bronchiectasis is surprisingly common and is increasing in incidence and prevalence in the UK, particularly in older age groups. Bronchiectasis is associated with a markedly increased mortality. Bronchiectasis is increasing in incidence and prevalence in the UK, and is associated with an increased mortality http://ow.ly/Sh3Y9

Autoimmune Diseases Co-occurring Within Individuals and Within Families: A Systematic Review

Background: Autoimmune diseases have been observed to coexist both within individuals and within families. It is unclear whether clinical reports of comorbid autoimmune diseases represent chance findings or true associations. This systematic review evaluates the current level of evidence on the coexistence of selected autoimmune diseases within individuals and families. We reviewed the associations among 4 TH1-associated autoimmune diseases: insulin-dependent diabetes mellitus, autoimmune (Hashimoto) thyroiditis, rheumatoid arthritis, and multiple sclerosis. Methods: Studies quantifying the coexistence between the selected diseases, published through March 2004, were identified from Medline and Embase searches. Study eligibility was determined on the basis of preestablished criteria, and relevant data were extracted according to a fixed protocol. We determined the prevalence of comorbid autoimmune disease according to index disease and then compiled summary statistics. Heterogeneity among studies was assessed by exact likelihood ratio tests and Monte Carlo inference. Results: We found 54 studies that met the eligibility criteria. Of these, 52 studies examined the coexistence of disease within individuals and 9 studies examined within-family associations. The majority of studies were uncontrolled and did not account for confounding factors. There was substantial evidence for heterogeneity among studies. Although inconclusive, the data appear to support an increased prevalence of autoimmune thyroiditis among patients with rheumatoid arthritis and those with insulin-dependent diabetes mellitus, and an inverse association between rheumatoid arthritis and multiple sclerosis. Conclusion: Although the available evidence does not permit firm conclusions regarding comorbidities among the selected autoimmune diseases, results are sufficiently suggestive to warrant further study.

The effect of number of births on women's mortality: Systematic review of the evidence for women who have completed their childbearing

Mortality in women who have completed their childbearing may increase with the number of births experienced because of maternal depletion or a trade-off between reproduction and mortality. We report a systematic review of the evidence on this association. We searched Medline, Embase, Popline, and the Science Citation Index for published and unpublished studies up to September 2003, and the book catalogues of relevant London libraries. Where necessary we also contacted authors for additional information. Mortality declined with increasing numbers of births in twelve historical cohorts, but in eight contemporary cohorts the highest mortality was seen in the nulliparous and in women with more than four births. All effects seen were small and there were few statistically significant results. Studies examining the relationship in other ways (such as by linear trends or by mean number of births by age at death) found inconsistent associations. We discuss methodological, social, and biological factors that may have affected these associations.