Pippa Oakeshott

Randomised controlled trial of screening for Chlamydia trachomatis to prevent pelvic inflammatory disease: the POPI (prevention of pelvic infection) trial

Objective To determine whether screening and treating women for chlamydial infection reduces the incidence of pelvic inflammatory disease over the subsequent 12 months. Design Randomised controlled trial. Setting Common rooms, lecture theatres, and student bars at universities and further education colleges in London. Participants 2529 sexually active female students, mean age 21 years (range 16-27). Intervention Participants completed a questionnaire and provided self taken vaginal swabs, with follow-up after one year. Samples were randomly allocated to immediate testing and treatment for chlamydial infection, or storage and analysis after a year (deferred screening controls). Main outcome measure Incidence of clinical pelvic inflammatory disease over 12 months. Results Baseline prevalence of chlamydia was 5.4% (68/1254) in screened women and 5.9% (75/1265) in controls. 94% (2377/2529) of women were followed up after 12 months. The incidence of pelvic inflammatory disease was 1.3% (15/1191) in screened women compared with 1.9% (23/1186) in controls (relative risk 0.65, 95% confidence interval 0.34 to 1.22). Seven of 74 control women (9.5%, 95% confidence interval 4.7% to 18.3%) who tested positive for chlamydial infection at baseline developed pelvic inflammatory disease over 12 months compared with one of 63 (1.6%) screened women (relative risk 0.17, 0.03 to 1.01). However, most episodes of pelvic inflammatory disease occurred in women who tested negative for chlamydia at baseline (79%, 30/38). 22% (527/2377) of women reported being tested independently for chlamydia during the trial. Conclusion Although some evidence suggests that screening for chlamydia reduces rates of pelvic inflammatory disease, especially in women with chlamydial infection at baseline, the effectiveness of a single chlamydia test in preventing pelvic inflammatory disease over 12 months may have been overestimated. Trial registration ClinicalTrials.gov NCT00115388.

Application of Framingham risk estimates to ethnic minorities in United Kingdom and implications for primary prevention of heart disease in general practice: cross sectional population based study

Abstract Objective: To compare the 10 year risk of coronary heart disease (CHD), stroke, and combined cardiovascular disease (CVD) estimated from the Framingham equations. Design:Population based cross sectional survey. Setting: Nine general practices in south London. Population: 1386 men and women, age 40-59 years, with no history of CVD (475 white people, 447 south Asian people, and 464 people of African origin), and a subgroup of 1069 without known diabetes, left ventricular hypertrophy, peripheral vascular disease, renal impairment, or target organ damage. Main outcome measures: 10 year risk estimates. Results: People of African origin had the lowest 10 year risk estimate of CHD adjusted for age and sex (7.0%, 95% confidence interval 6.5 to 7.5) compared with white people (8.8%, 8.2 to 9.5) and south Asians (9.2%, 8.6 to 9.9) and the highest estimated risk of stroke (1.7% (1.5 to 1.9), 1.4% (1.3 to 1.6), 1.6% (1.5 to 1.8), respectively). The estimate risk of combined CVD, however, was highest in south Asians (12.5%, 11.6 to 13.4) compared with white people (11.9%, 11.0 to 12.7) and people of African origin (10.5%, 9.7 to 11.2). In the subgroup of 1069, the probability that a risk of CHD 15% would identify risk of combined CVD 20% was 91% in white people and 81% in both south Asians and people of African origin. The use of thresholds for risk of CHD of 12% in south Asians and 10% in people of African origin would increase the probability of identifying those at risk to 100% and 97%, respectively. Conclusion: Primary care doctors should use a lower threshold of CHD risk when treating mild uncomplicated hypertension in people of African or south Asian origin.

Is Mycoplasma genitalium in Women the “New Chlamydia?” A Community-Based Prospective Cohort Study

BACKGROUND The role of Mycoplasma genitalium in pelvic inflammatory disease is unclear. We conducted a cohort study to determine the prevalence and predictors of M. genitalium infection in female students, to explore its role in pelvic inflammatory disease and to estimate its annual incidence and persistence rate. METHODS Two thousand three hundred seventy-eight multiethnic, sexually active female students (mean age, 21 years) provided duplicate self-taken vaginal samples for a chlamydia screening trial. From this population, 2246 (94%) were followed up after 12 months and assessed for incidence of clinical pelvic inflammatory disease. In addition, 900 women (38%) returned follow-up samples via the postal service 11-32 months after recruitment. Stored samples were tested for M. genitalium. RESULTS The prevalence of M. genitalium at baseline was 3.3% (78 of 2378 women; 95% confidence interval [CI], 2.6%-4.1%). Infection was more common in women reporting ≥ 2 sexual partners in the previous year, those with bacterial vaginosis, women aged < 18 years, women of black ethnicity, and smokers. Multiple partners and bacterial vaginosis were independent risk factors for M. genitalium (adjusted risk ratio, 2.23 [95% CI, 1.39-3.58] and 2.54 [95% CI, 1.61-4.01], respectively). The incidence of pelvic inflammatory disease over 12 months was 3.9% (3 of 77 women) among women with M. genitalium infection, compared with 1.7% (36 of 2169 women) among those without infection (risk ratio, 2.35; 95% CI, 0.74-7.46; P = .14). Annual incidence of M. genitalium infection in 873 women without M. genitalium infection at baseline who returned samples via the postal service was 0.9% (95% CI, 0.5%-1.6%). Seven (26%; 95% CI, 9%-43%) of 27 women with M. genitalium infection at baseline remained positive after 12-21 months; genotyping results suggest that these were persistent infections. CONCLUSIONS M. genitalium infection is unlikely to be a major risk factor for clinical pelvic inflammatory disease in this population.

Link between the CSF shunt and achievement in adults with spina bifida

OBJECTIVES A few enterprising adults with shunt treated spina bifida live independently in the community, have a job in competitive employment, and drive to work in their own car. By contrast others with similar disability but lacking their motivation remain dependent on care and supervision. The aim of this study was to identify events in the history of their shunt which may have influenced their subsequent achievement. METHODS Between June 1963 and January 1971 117 babies born in East Anglia with open spina bifida had their backs closed regardless of the severity of their condition. When reviewed in 1997 every case was ascertained. Sixty had died and the 57 survivors had a mean age of 30. These were assigned to two groups: achievers and non-achievers, according to their attainments in independence, employment, and use of a car. RESULTS Of the 57 survivors nine had no shunt and eight of these were achievers. All were of normal intelligence (IQ⩾80) and only one was severely disabled. Of the 48 with shunts only 20 were achievers (OR 11.2, 95% confidence interval (95% CI) 1.3–96.8). Lack of achievement in these 48 was associated with revisions of the shunt, particularly when revisions were performed after the age of 2. Sixteen patients had never required a revision and 11 (69%) were achievers; 10 had had revisions only during infancy and five (50%) were achievers; 22 had had revisions after their second birthday and only four (18%) were achievers (p<0.001). Elective revisions were not performed in this cohort and in 75% of patients revisions had been preceded by clear symptoms of raised intracranial pressure. CONCLUSION Revisions of the shunt, particularly after the age of 2, are associated with poor long term achievement in adults with spina bifida.

Expectation of life and unexpected death in open spina bifida: a 40‐year complete, non‐selective, longitudinal cohort study

Aim  The aim of our study was to investigate survival and causes of death in a complete cohort of open spina bifida at the mean age of 40 years.

Prevalence of Mycoplasma genitalium in early pregnancy and relationship between its presence and pregnancy outcome.

Mycoplasma genitalium is associated with cervicitis and pelvic inflammatory disease but little is known about its role in pregnancy. We investigated the prevalence of M. genitalium by polymerase chain reaction assay on urine specimens from 1216 pregnant women (mean age 31years) presenting before 10 weeks of gestation in 32 general practices. The prevalence of M. genitalium was 0.7% (6/915, 95% CI 0.1–1.2). It was more common in women aged <20 years, women of Afro‐Caribbean or black African ethnic origin, women in social classes 3–5 and single women. Only one woman with M. genitalium infection miscarried, and none of those followed up to term had a preterm birth, although the numbers were small. The low prevalence of M. genitalium infection suggests it is unlikely to be an important risk factor in adverse pregnancy outcome in healthy women in the community.

Risk factors associated with pelvic inflammatory disease

Objective: To investigate factors associated with pelvic inflammatory disease (PID). Methods: A case–control study was used to investigate demographic and behavioural factors, and causative agents associated with PID. Results: A total of 381 participants were recruited: 140 patients, and 105 and 136 controls in tubal ligation and general practice groups, respectively. When compared with a PID-free tubal ligation control group, increased risk of PID was associated with: age <25 years; age at first sexual intercourse <20 years; non-white ethnicity; not having had children; a self-reported history of a sexually transmitted disease; and exposure to Chlamydia trachomatis. When compared with a general practice control group, increased risk was associated with: age <25 years; age at first sexual intercourse <15 years; lower socioeconomic status; being single; adverse pregnancy outcome; a self-reported history of a sexually transmitted disease; and exposure to C trachomatis. Of the cases, 64% were not associated with any of the infectious agents measured in this study (idiopathic). Conclusions: A high proportion of cases were idiopathic. PID control strategies, which currently focus on chlamydial screening, have to be reviewed so that they can prevent all cases of PID. Behavioural change is a key factor in the primary prevention of PID, and potential modifiable risk factors were associated with PID.

Preventing transmission of maternally inherited mitochondrial DNA diseases.

#### Summary points #### Methods We used our personal archive of references, Medline searches, and consultation with other experts in the field to produce this review. It is derived from 22 years of research and 11 years of genetic counselling in mitochondrial DNA diseases. Maternally inherited mutations of mitochondrial DNA can be asymptomatic or cause illnesses such as developmental regression, deafness, blindness, neuropathy, diabetes, cardiomyopathy, and liver failure. Families who have lost a child from a mitochondrial DNA disease (fig 1⇓) often seek genetic counselling before trying to conceive again. They may also need support from their general practitioner when deciding between treatments that could increase their chances of having a healthy baby, but some doctors have limited knowledge of current genetic advances. In February 2008, an important step towards nuclear transfer in humans was reported.1 The nucleus of a fertilised human egg was transplanted into an enucleated recipient egg (oocyte) from an unrelated donor, resulting in an embryo with “three genetic parents.” In future, this technique might help to prevent transmission of maternally inherited mitochondrial DNA diseases, a range of potentially devastating illnesses caused by defects in mitochondrial function. Meanwhile, other in vitro fertilisation related interventions have recently become available that should be offered more widely. Here, we explain why the management of mitochondrial DNA diseases has lagged behind the genetics …

Frequency and risk factors for prevalent, incident, and persistent genital carcinogenic human papillomavirus infection in sexually active women: community based cohort study

Objective To investigate frequency and risk factors for prevalent, incident, and persistent carcinogenic human papillomavirus (HPV) in young women before the introduction of immunisation against HPV types 16 and 18 for schoolgirls. Design Cohort study Setting 20 London universities and further education colleges. Participants 2185 sexually active female students, mean age 21 years (range 16-27), 38% from ethnic minorities, who took part in the POPI (prevention of pelvic infection) chlamydia screening trial in 2004-08 and who provided duplicate, self taken vaginal swabs and completed questionnaires at baseline. At follow-up, a median of 16 months later, 821 women (38%) returned repeat vaginal swabs by post. In 2009-10, stored samples were tested for HPV. Results Samples from 404/2185 (18.5% (95% CI 16.9% to 20.2%)) of the cohort were positive for carcinogenic HPV at baseline, including 15.0% (327) positive for non-vaccine carcinogenic genotypes. Reporting two or more sexual partners in the previous year and concurrent Chlamydia trachomatis or bacterial vaginosis were independent risk factors for prevalent vaginal HPV infection. Infection with one or more new HPV types was found in 17.7% (145/821) of follow-up samples, giving an estimated annual incidence of carcinogenic HPV infection of 12.9% (95% CI 11.0% to 15.0%). Incident infection was more common in women reporting two or more partners in the previous year, aged<20, of black ethnicity, or with C trachomatis vaginosis at baseline. Multiple partners was the only independent risk factor for incident infection (adjusted relative risk 1.99 (95% CI 1.46 to 2.72)). Of 143 women with baseline carcinogenic HPV infection, 20 (14% (8.3% to 19.7%) had infection with the same carcinogenic HPV type(s) detected after 12-28 months. Of these women, 13 (65%) had redetected infection with HPV 16 or 18, and nine (45%) with non-vaccine carcinogenic HPV genotypes. Conclusion In the first UK cohort study of carcinogenic HPV in young women in the community, multiple sexual partners was an independent predictor of both prevalent and incident infection. Infection with non-vaccine carcinogenic genotypes was common. Although current HPV vaccines offer partial cross protection against some non-vaccine carcinogenic HPV types, immunised women will still need cervical screening.

Prevalence of human papillomavirus (HPV) infections in sexually active adolescents and young women in England, prior to widespread HPV immunisation

INTRODUCTION The introduction of an HPV immunisation programme in England should result in a significant reduction in the prevalence of vaccine type infections in young women. Here we describe type-specific HPV prevalence in three samples of the young female population in England, prior to the beginning of mass immunisation in 2008. METHODS Residual vulva-vaginal swab samples from females aged under 25 years undergoing chlamydia testing as part of the National Chlamydia Screening Programme (NCSP) or Prevention of Pelvic Infection (POPI) trial were collected from sites across England, together with available demographic and sexual behaviour data. Residual samples were screened for HPV infection using the Hybrid Capture 2 (hc2) HPV DNA Test, including the high-risk (HR) and low-risk (LR) probes. Hc2 positive samples were genotyped using the Roche Linear Array (LA) HPV Genotyping Test. RESULTS A total of 3829 samples were included: 2369 from 16 to 24 year old NCSP participants, 275 from 13 to 15 year old NCSP participants and 1185 from 16 to 24 year old POPI participants. Variations in HPV prevalence between and within the different samples followed a pattern largely consistent with differences in sexual behaviour. The prevalence of total HR HPV infection, of HPV 16 and/or 18 (16/18) infection and of five HR HPV types closely related to HPV 16/18 (HPV 31, 33, 45, 52 or 58) amongst 16-24 year old NCSP participants was 35% (95% CI 33-37%), 18% (95% CI 16-19%), and 16% (95% CI 14-18%), respectively. Risk of HR HPV infection increased with age during the teen years and was higher in women who reported two or more sexual partners in the last year and in women with chlamydia infection. Approximately half of women with HPV 16/18 infection also had another non-vaccine HR HPV type present. CONCLUSIONS Prior to HPV immunisation, there was a high prevalence of HPV infections in the lower genital tract of young, sexually active females in England. The overall, type-specific, and multiple infection prevalence closely reflected age and sexual activity. These data provide a baseline against which the early impact of HPV immunisation on the prevalence of HPV 16/18 and closely related types in young women can be measured, in order to inform immunisation and cervical screening policies.