Bethan Davies

Risk of reproductive complications following chlamydia testing: a population-based retrospective cohort study in Denmark

BACKGROUND Uncertainty in the risk of reproductive complications (pelvic inflammatory disease, ectopic pregnancy, and tubal factor infertility) following chlamydia infection and repeat infection hampers the design of evidence-based chlamydia control programmes. We estimate the association between diagnosed chlamydia and episodes of hospital health care (inpatient, outpatient, and emergency department) for a reproductive complication. METHODS We constructed and analysed a retrospective population-based cohort of women aged 15-44 years from administrative records in Denmark (1995-2012). We used a subset of the national Danish Chlamydia Study. The master dataset contains all residents of Denmark (including Greenland) who had a positive chlamydia test recorded by a public health microbiology laboratory from Jan 1, 1992, to Nov 2, 2011. Individuals were randomly matched (by age and sex) to four individuals drawn from the population register (Danish Civil Registration System) who did not have a positive chlamydia test during this interval. The outcomes in the study were hospital episodes of health-care (inpatient, outpatient, and emergency department) with a diagnosis of pelvic inflammatory disease, ectopic pregnancy, or tubal factor infertility. FINDINGS The 516 720 women (103 344 positive, 182 879 negative, 230 497 never-tested) had a mean follow-up of 7·96 years. Compared with women with only negative tests, the risk of each complication was 30% higher in women with one or more positive tests (pelvic inflammatory disease, adjusted hazard ratio [AHR] 1·50 [95% CI 1·43-1·57]; ectopic pregnancy, AHR 1·31 [1·25-1·38]; tubal factor infertility, AHR 1·37 [1·24-1·52]) and 60% lower in women who were never-tested (pelvic inflammatory disease, AHR 0·33 [0·31-0·35]; ectopic pregnancy, AHR 0·42 [0·39-0·44]; tubal factor infertility AHR 0·29 [0·25-0·33]). A positive test had a minor absolute impact on health as the difference in the lifetime incidence of complications was small between women who tested positive and those who tested negative (pelvic inflammatory disease, 0·6%; ectopic pregnancy, 0·2%; tubal factor infertility, 0·1%). Repeat infections increased the risk of pelvic inflammatory disease by a further 20% (AHR 1·20, 95% CI 1·11-1·31). INTERPRETATION A single diagnosed chlamydia infection increased the risk of all complications and a repeat diagnosed infection further increased the risk of pelvic inflammatory disease. Therefore, control programmes must prevent first and repeat infections to improve womens reproductive health. FUNDING Unrestricted partial funding from Frederiksberg Kommune, Frederiksberg, Denmark. BD held an Medical Research Council Population Health Scientist Fellowship (G0902120). KT held an National Institute for Health Research Post-Doctoral Fellowship 2009-02-055.

How robust are the natural history parameters used in chlamydia transmission dynamic models? A systematic review

Transmission dynamic models linked to economic analyses often form part of the decision making process when introducing new chlamydia screening interventions. Outputs from these transmission dynamic models can vary depending on the values of the parameters used to describe the infection. Therefore these values can have an important influence on policy and resource allocation. The risk of progression from infection to pelvic inflammatory disease has been extensively studied but the parameters which govern the transmission dynamics are frequently neglected. We conducted a systematic review of transmission dynamic models linked to economic analyses of chlamydia screening interventions to critically assess the source and variability of the proportion of infections that are asymptomatic, the duration of infection and the transmission probability. We identified nine relevant studies in Pubmed, Embase and the Cochrane database. We found that there is a wide variation in their natural history parameters, including an absolute difference in the proportion of asymptomatic infections of 25% in women and 75% in men, a six-fold difference in the duration of asymptomatic infection and a four-fold difference in the per act transmission probability. We consider that much of this variation can be explained by a lack of consensus in the literature. We found that a significant proportion of parameter values were referenced back to the early chlamydia literature, before the introduction of nucleic acid modes of diagnosis and the widespread testing of asymptomatic individuals. In conclusion, authors should use high quality contemporary evidence to inform their parameter values, clearly document their assumptions and make appropriate use of sensitivity analysis. This will help to make models more transparent and increase their utility to policy makers.

Heterogeneity in Risk of Pelvic Inflammatory Diseases After Chlamydia Infection: A Population-Based Study in Manitoba, Canada

Background. The association between chlamydia infection and pelvic inflammatory disease (PID) is a key parameter for models evaluating the impact of chlamydia control programs. We quantified this association using a retrospective population-based cohort. Methods. We used administrative health data sets to construct a retrospective population-based cohort of women and girls aged 12–24 years who were resident in Manitoba, Canada, between 1992 and 1996. We performed survival analysis on a subcohort of individuals who were tested for chlamydia to estimate the risk of PID diagnosed in a primary care, outpatient, or inpatient setting after ≥1 positive chlamydia test. Results. A total of 73 883 individuals contributed 625 621 person years of follow-up. Those with a diagnosis of chlamydia had an increased risk of PID over their reproductive lifetime compared with those who tested negative (adjusted hazard ratio [AHR], 1.55; 95% confidence interval [CI], 1.43–1.70). This risk increased with each subsequent infection: the AHR was 1.17 for first reinfection (95% CI, 1.06–1.30) and 1.35 for the second (95% CI, 1.04–1.75). The increased risk of PID from reinfection was highest in younger individuals (AHR, 4.55 (95% CI, 3.59–5.78) in individuals aged 12–15 years at the time of their second reinfection, compared with individuals older than 30 years). Conclusions. There is heterogeneity in the risk of PID after a chlamydia infection. Describing the progression to PID in mathematical models as an average rate may be an oversimplification; more accurate estimates of the cost-effectiveness of screening may be obtained by using an individual-based measure of risk. Health inequalities may be reduced by targeting health promotion interventions at sexually active girls younger than 16 years and those with a history of chlamydia.

Risk of pelvic inflammatory disease after Chlamydia infection in a prospective cohort of sex workers.

Introduction There is uncertainty in the risk of pelvic inflammatory disease (PID) after chlamydia infection. We analyzed a prospective cohort of sex workers recruited in London between 1985 and 1993 to estimate the risk of PID after a diagnosed case of chlamydia. Materials and Methods Chlamydia and gonorrhea were defined as “recent” if they occurred during the most recent 6 months of follow-up or “previous” if they were more than 6 months ago, were the second infection during follow-up, or occurred before the study. Pelvic inflammatory disease was diagnosed using clinical criteria. We used Cox proportional hazards regression to estimate the association between chlamydia and PID controlled for gonorrhea. Results Three hundred seven women contributed 401.2 person-years of follow-up. The rate of PID in women with recent chlamydia was 27.4 per 100 person-years compared with 11.2 in those without recent chlamydia. Recent and previous chlamydia significantly increased the risk of PID; this association persisted but was no longer significant after controlling for age and history of gonorrhea: recent chlamydia (adjusted hazard ratio [aHR], 2.0; 95% confidence interval [CI], 0.7–5.5), previous chlamydia (aHR, 1.8; 95% CI, 1.0–3.5), previous gonorrhea (aHR, 2.3; 95% CI, 1.1–4.6), and age (HR, 0.9; 95% CI, 0.9–1.0). Discussion Women with recent or previous chlamydia are at increased risk for PID. However, this association may be explained by previous exposure to gonorrhea, which was found to increase the risk of PID after a future chlamydia infection.

Pelvic inflammatory disease risk following negative results from chlamydia nucleic acid amplification tests (NAATs) versus non-NAATs in Denmark: A retrospective cohort

Background Nucleic Acid Amplification Tests (NAATs) are the recommended test type for diagnosing Chlamydia trachomatis (chlamydia). However, less sensitive diagnostic methods—including direct immunofluorescence (IF) and enzyme-linked immunoassay (ELISA)—remain in use in lower resourced settings. We estimate the risk of pelvic inflammatory disease (PID) following undiagnosed infection in women tested with non-NAATs and estimate the health gain from using accurate diagnostic tests. Methods and findings We used Denmark’s national Chlamydia Study dataset to extract all chlamydia tests performed in women aged 15–34 years (1998–2001). Tests were categorised as non-NAAT (IF/ELISA) or NAAT and limited to each woman’s first test in the study period. We linked test data to hospital presentations for PID within 12 months from the Danish National Patient Register. The study included 272,105 women with a chlamydia test, just under half (44.78%, n = 121,857) were tested using NAATs. Overall, 6.38% (n = 17,353) tested positive for chlamydia and 0.64% (n = 1,732) were diagnosed with PID within 12 months. The risk of PID following a positive chlamydia test did not differ by test type (NAAT 0.81% [95% CI 0.61–1.00], non-NAAT 0.78% [0.59–0.96]). The risk of PID following a negative test was significantly lower in women tested with NAATs compared to non-NAATs (0.55% [0.51–0.59] compared to 0.69% [0.64–0.73]; adjusted odds ratio (AOR) 0.83 [0.75–0.93]). We estimate that 18% of chlamydia infections in women tested with a non-NAAT were undiagnosed and that the risk of progression from undiagnosed chlamydia infection to PID within 12 months was 9.52% (9.30–9.68). Using non-NAATs could lead to an excess 120 cases of PID per 100,000 women tested compared to using NAATs. The key limitations of this study are under ascertainment of PID cases, misclassification bias in chlamydia and PID exposure status, bias to the association between clinical presentation and test type and the presence of unmeasured confounders (including other sexually transmitted infection [STI] diagnoses and clinical indication for chlamydia test). Conclusion This retrospective observational study estimates the positive impact on women’s reproductive health from using accurate chlamydia diagnostic tests and provides further evidence for restricting the use of inferior tests. Women with a negative chlamydia test have a 17% higher adjusted risk of PID by 12 months if they are tested using a non-NAAT compared to a NAAT.

Comparison of the Population Excess Fraction of Chlamydia trachomatis Infection on Pelvic Inflammatory Disease at 12-months in the Presence and Absence of Chlamydia Testing and Treatment: Systematic Review and Retrospective Cohort Analysis

Background The impact of Chlamydia trachomatis (chlamydia) control on the incidence of pelvic inflammatory disease (PID) is theoretically limited by the proportion of PID caused by chlamydia. We estimate the population excess fraction (PEF) of treated chlamydia infection on PID at 12-months in settings with widespread chlamydia control (testing and treatment) and compare this to the estimated PEF of untreated chlamydia. Methods We used two large retrospective population-based cohorts of women of reproductive age from settings with widespread chlamydia control to calculate the PEF of treated chlamydia on PID at 12-months. We undertook a systematic review to identify further studies that reported the risk of PID in women who were tested for chlamydia (infected and uninfected). We used the same method to calculate the PEF in eligible studies then compared all estimates of PEF. Results The systematic review identified a single study, a randomised controlled trial of chlamydia screening (POPI-RCT). In the presence of testing and treatment <10% of PID at 12-months was attributable to treated (baseline) chlamydia infections (Manitoba: 8.86%(95%CI 7.15–10.75); Denmark: 3.84%(3.26–4.45); screened-arm POPI-RCT: 0.99%(0.00–29.06)). In the absence of active chlamydia treatment 26.44%(11.57–46.32) of PID at 12-months was attributable to untreated (baseline) chlamydia infections (deferred-arm POPI-RCT). The PEFs suggest that eradicating baseline chlamydia infections could prevent 484 cases of PID at 12-months per 100,000 women in the untreated setting and 13–184 cases of PID per 100,000 tested women in the presence of testing and treatment. Conclusion Testing and treating chlamydia reduced the PEF of chlamydia on PID by 65% compared to the untreated setting. But in the presence of testing and treatment over 90% of PID could not be attributed to a baseline chlamydia infection. More information is needed about the aetiology of PID to develop effective strategies for improving the reproductive health of women.

A pathway to chlamydia control: updated ECDC guidance

In 2009, the European Centre for Disease Prevention and Control (ECDC) published guidance on chlamydia ( Chlamydia trachomatis ) control in Europe.1 In it we recommended that EU/EEA member states ensure the provision of basic resources and systems (for diagnosis, case and partner management) before embarking on any expanded screening programme. This guidance was based on evidence first that there was a huge variation in availability of clinical services for chlamydia across member states, and second that the evidence for population level programmes was missing.1 ,2 This month ECDC has released updated guidance that we developed with the support of ECDC experts following a programme of work to update the evidence, including an extensive review of the epidemiology and natural history of chlamydia and the clinical and cost-effectiveness of screening programmes.3 The team also repeated the survey of member states, and assessed the impact of the original guidance.4 ,5 The survey showed that more countries had established essential diagnostic and management facilities and guidelines;6 it was hard to attribute this …

Informal carers’ perspectives on the delivery of acute hospital care for patients with dementia: a systematic review

BackgroundProviding high quality acute hospital care for patients with dementia is an increasing challenge as the prevalence of the disease rises. Informal carers of people with dementia are a critical resource for improving inpatient care, due to their insights into patients’ needs and preferences. We summarise informal carers’ perspectives of acute hospital care to inform best practice service delivery.MethodsWe conducted a systematic search of bibliographic databases and sought relevant grey literature. We used thematic synthesis analysis to assimilate results of the studies and describe components of care that influence perceived quality.ResultsTwenty papers met the inclusion criteria. Findings identified four overarching components of care that influenced carer experience and their perceptions of care quality: ‘Patient care’, ‘Staff interactions’, ‘Carer’s situation’ and ‘Hospital environment’. Need for improvement was identified in staff training, provision of help with personal care needs, and dignified treatment of patients. Carers need to be informed, involved and supported during hospital admission in order to promote the most positive experience.ConclusionThis review identifies common perspectives of informal carers of people with dementia in the acute hospital setting and highlights important areas to address to improve the experience of an admission for both carer and patient.

Patterns in chlamydia detection rate in young adults aged 15–24 years in England, 2012–15: longitudinal analysis of routine data

Abstract Background The National Chlamydia Screening Programme (NCSP) in England recommends chlamydia testing for sexually active young adults (aged 15–24 years). The Public Health Outcomes Framework (PHOF) suggests that implementation and delivery of the NCSP should identify 2300 cases or more of chlamydia per 100 000 residents (15–24 years old). The commissioning of chlamydia screening moved to local authorities in 2013. We describe performance of local authorities against the PHOF chlamydia screening recommendation. Methods We used chlamydia test data from Public Health England (2012–15), index of multiple deprivation (2015) data from National Office of Statistics, and population data to describe the association between the proportion of local authorities achieving the PHOF chlamydia detection rate recommendation and deprivation at local authority level, adjusted for population size and proportion of tests performed in a genitourinary medicine setting. Findings The number of chlamydia tests performed within the NCSP declined by 17% (1 860 000 in 2012 to 1 538 000 in 2015) over the study period. The proportion of local authorities that achieved the PHOF chlamydia diagnosis rate recommendation fell 39% (from 23% [75/324] in 2012 to 14% [45/324] in 2015). Throughout the 4-year period, local authorities in the most-deprived quintile were more likely to attain the recommendation than were local authorities in the least-deprived quintile (adjusted odds ratio 10·6 (95% CI 3·0–37·9) in 2012, 15·9 (2·0–129·5) in 2015). Interpretation There has been a reduction in the number of chlamydia tests performed within the NCSP and a larger reduction in the proportion of local authorities meeting the chlamydia diagnosis rate recommendation since 2012. This finding suggests that the decline in testing may disproportionately affect those most at risk of chlamydia infection. There are also marked inequalities in attainment of the recommendation, including local area deprivation. Further analysis is needed to understand whether this observed decline in activity could impact chlamydia incidence or prevalence and to understand the association between factors at the local authority level and NCSP activity. Funding HW and BD receive funding from the Imperial National Institute for Health Research Biomedical Research Centre.

Chlamydia diagnosis rate in England in 2012: an ecological study of local authorities

Objectives Local authorities (LAs) in England commission chlamydia screening as part of the National Chlamydia Screening Programme. It is recommended that LAs achieve a chlamydia diagnosis rate of ≥2300 cases per 100 000 population aged 15–24. We describe national patterns in attainment of the chlamydia diagnosis rate recommendation and possible implications of using it to measure LA-level performance. Methods We used publicly available data sets from England (2012) to explore the association between LAs attaining the recommended chlamydia diagnosis rate and population size, socioeconomic deprivation, test setting and sex. Results We used data from 1 197 121 recorded chlamydia tests in females and 564 117 in males. The chlamydia diagnosis rate recommendation was achieved by 22% (72/324) of LAs overall (43% female population; 8% male population). LAs in the highest deprivation quintile were more likely to reach the recommendation than those in the least-deprived quintile for both sexes (women: unadjusted prevalence ratio (UPR) 7.43, 95% CI 3.65 to 15.11; men: UPR 7.00, 95% CI 1.66 to 29.58). The proportion of tests performed in genitourinary medicine clinics was negatively associated with attainment of the recommended diagnosis rate (UPR 0.95, 0.93 to 0.97). Conclusions Chlamydia diagnosis rate recommendations that reflect local area deprivation (as a proxy for disease burden) may be more appropriate than a single national target if the aim is to reduce health inequalities nationally. We suggest LAs monitor their chlamydia diagnosis rate, test coverage and test positivity across a range of measures (including setting and sex) and pre/post changes to commissioned services. Critical evaluation of performance against the recommendation should be reflected in local commissioning decisions.