The purpose of this study was to quantify the impact of recurrent genital herpes (RGH) on health-related quality of life, healthcare resource and workplace productivity. This was a cross-sectional survey conducted in 5 countries (Australia, Denmark, Italy, The Netherlands and UK). Patients with a confirmed history of RGH completed the MOS 36-Item Short Form Health Survey (SF-36) and the Recurrent Genital Herpes Quality of Life questionnaire (RGHQoL). Questionnaires addressing frequency of access to healthcare services and workplace productivity were also completed and patients' medical history was obtained. Scores for 6 of the 8 domains of the SF-36 were significantly lower (P<0.001) i.e. worse, compared with scores for the normal population. The RGHQoL score was significantly lower in patients experiencing more frequent or more severe recurrences. Forty-five per cent of patients estimated that their work effectiveness was reduced by between 25% and 50% due to genital herpes symptoms.

Objective: To investigate whether suppressive antiviral therapy improves health related quality of life in patients with recurrent genital herpes. Methods: Health related quality of life was measured using the disease specific recurrent genital herpes quality of life questionnaire (RGHQoL) as part of a randomised, double blind, 52 week, placebo controlled, dose ranging study of once and twice daily valaciclovir or aciclovir for the suppression of recurrent genital herpes in patients with six or more recurrences per year. Results: Of 1479 participants, 1349 patients completed the baseline questionnaire. There were no significant baseline diVerences in RGHQoL score between any of the treatment groups. After 3 months there were significantly greater improvements in mean RGHQoL scores for all active treatment groups compared with placebo (p<0.05). Mean RGHQoL score improvements from baseline remained significantly higher in the active treatment groups than in the placebo group after 6 and 12 months, indicating that the improved health related quality of life in patients receiving suppressive antiviral therapy was sustained over a prolonged period of time. Conclusion: Suppressive antiviral therapy is an eVective strategy for improving the quality of life of patients with recurrent genital herpes. These improvements in quality of life are sustained over time, thus enhancing the clinical benefit in the long term management of this condition. (Sex Transm Inf 1999;75:398-402)

and treatment failure among men who have sex with men (MSM), heterosexual men and women, diagnosed with repeat chlamydia infection within 1-4 months after treatment with azithromycin. Methods Participants completed an online survey capturing treatment and sexual behaviour data since initial diagnosis. Specimens from initial and repeat infections were included in the study. Chlamydia serovars were determined using quantitative PCR assays. When the same serovar was detected in both specimens for participants, MLST was used to further discriminate between genotypes. An algorithm based on genotype and sexual behaviour data was used to differentiate treatment failure from reinfection. Results There were 600 participants (200 MSM, 200 heterosexual males, 200 females) diagnosed with chlamydia. Of 301/600 who retested between 1-4 months: 258/301 (85.7%) were cured (treated and negative on retest); 4/301 (1.3%) had a definite reinfection (positive retest and different genotype); 19/301 (6.3%) had probable reinfection (positive retest, same genotype and reported unprotected sex with the same or a different partner); 17/301 (5.6%) had possible treatment failure (positive retest, same genotype and reported not having sex or always using condoms); 1/301 (0.3%) had a persistent infection (positive retest, same genotype and no documented treatment); and 2/301 (0.7%) could not be categorised due to insufficient information. Possible treatment failures were more common in MSM (11.3%, 12/106) vs other groups (2.6%, 5/195; p < 0.01). Among the possible treatment failures in MSM, 10/12 (83.3%) were initial rectal samples. Conclusion Treatment failure was common in MSM with rectal chlamydia, suggesting the need for treatment efficacy trials. Disclosure of interest statement No conflict of interest is declared.

BackgroundOvarian cancer is the most lethal gynaecological malignancy, accounting for approximately 185,000 deaths worldwide in 2018. The majority of patients will experience recurrence of disease. Therefore, there is an urgent need for the development of further therapies to improve patient survival. Tumour infiltrating lymphocyte (TIL) therapy has shown clear efficacy in immunogenic cancers, and TIL can be readily expanded ex vivo from samples of high grade serous ovarian cancer (HGSOC). Key indicators of effective TIL products for infusion are high TIL yield and functionality against autologous tumour. Blockade of checkpoint proteins is effective in increasing TIL yield and functional response from ovarian cancer TIL cultures. However, it is unknown whether blockade of other key checkpoints, including programmed death ligand-1 (PD-1), T cell immunoglobulin mucin-3 (TIM-3) and lymphocyte activation gene-3 (LAG-3) increase TIL yield in ex vivo cultures from HGSOC samples.Materials and MethodsTIL cultures were generated from surgically resected HGSOC tumour samples and were incubated with CD3/CD28 Dynabeads. 3000IU/mL recombinant interleukin-2 (IL-2) was added on alternate days for 7 days before beads were removed. 1000IU/mL IL-2 was added on alternate days for a further 12 days of culture. In cohort 1, 10µg/mL αPD-1, αTIM-3 or αLAG-3 antibodies were added at initiation of TIL cultures only. In cohort 2, 10µg/mL αPD-1, αTIM-3 or αLAG-3 antibodies were added on alternate days until Day 19. Interferon gamma (IFN-γ) release in response to TIL co-culture with autologous tumour cultures was measured with a human IFN-γ ELISA kit. Data are presented as mean±SEM.ResultsAddition of checkpoint inhibitors at the initiation of HGSOC TIL culture in cohort 1 increased TIL expansion above untreated control in αPD-1 (1.20±0.04 fold, P<0.01, n=9) and αLAG-3 (1.31±0.08 fold, P<0.001, n=9) but not αTIM-3 treated cultures. However, intermittent dosing of HGSOC cultures in cohort 2 with either αPD-1, αTIM-3 or αLAG-3 antibodies did not increase TIL expansion above untreated cultures. In cohort 1, IFN-γ secretion was increased above untreated control in at least one culture treated with a checkpoint inhibitor in 5/7 patients. However, there was no overall fold change in IFN-γ secretion in either αPD-1, αTIM-3 or αLAG-3 treated cultures.ConclusionsThis data suggests that initial blockade of checkpoint proteins is effective in increasing the ex vivo expansion of TIL from HGSOC tumours, thus providing a method of improving the efficacy of TIL products in ovarian cancer patients.FundingGO was funded through a CRUK Manchester Centre Clinical Fellowship. PJ was in receipt of a bursary from the Emma Gyles Bursary Fund. The project was funded by TESARO Inc.Disclosure InformationC.A. Waddell: None. M.J. Price: None. P. Johnson: None. R.J. Edmondson: None. G.L. Owens None.

Objectives: To assess the accuracy and completeness of information provided by websites selling home self-sampling and testing kits for COVID-19. Design: Cross-sectional observational study. Setting: All websites (n=27) selling direct to user home self-sampling and testing for COVID-19 (41 tests) in the UK (39 tests) and US (2 tests) identified by a website search on 23rd May 2020. Main outcome measures: Thirteen predefined basic information items to communicate to a user, including who should be tested, when and how testing should be done, test accuracy, and interpretation of results. Results: Many websites did not provide the name or manufacturer of the test (32/41; 78%), when to use the test (10/41; 24%), test accuracy (12/41; 29%), and how to interpret results (21/41; 51%). Sensitivity and specificity were the most commonly reported test accuracy measures (either reported for 27/41 (66%) tests); we could only link these figures to manufacturers documents or publications for four (10%) tests. Predictive values, most relevant to users, were rarely reported (five [12%] tests reported positive predictive values). For molecular virus tests, 9/23 (39%) websites explained that test positives should self-isolate, and 8/23 (35%) explained that test negatives may still have the disease. For antibody tests, 12/18 (67%) websites explained that testing positive does not necessarily infer immunity from future infection. Seven (39%) websites selling antibody tests claimed the test had a CE mark, when they were for a different intended use (venous blood rather than finger-prick samples). Conclusions: At the point of online purchase of home self-sampling COVID-19 tests, users in the UK are provided with incomplete, and in some cases misleading information on test accuracy, intended use and test interpretation. Best practice guidance for communication about tests to the public should be developed and enforced for online sales of COVID-19 tests.

Defective DNA damage response (DDR) pathways allow cancer cells to accrue genomic aberrations and evade normal cellular growth checkpoints. Defective DDR also determines response to chemotherapy. However, the interaction and overlap between the two double strand repair pathways and the three single strand repair pathways is complex, and has remained poorly understood. Here we show that, in ovarian cancer, a disease hallmarked by chromosomal instability, explant cultures show a range of DDR abrogation patterns. Defective homologous recombination (HR) and non-homologous end joining (NHEJ) are near mutually exclusive with HR deficient (HRD) cells showing increased abrogation of the single strand repair pathways compared to NHEJ defective cells. When combined with global markers of DNA damage, including mitochondrial membrane functionality and reactive oxygen species burden, the pattern of DDR abrogation allows the construction of DDR signatures which are predictive of both ex vivo cytotoxicity, and more importantly, patient outcome.

No abstract

Background The risk of Pelvic Inflammatory Disease (PID) and Ectopic Pregnancy (EP) from Chlamydia are crucial in estimating the cost-effectiveness of screening, but they remain poorly understood. Methods We use evidence from RCTs of screening and controlled observational studies to estimate the risk of PID following Chlamydia and the probability PID would be prevented by annual testing. The studies are synthesised using a model that allows for the possibility that the rate of developing PID is higher in the period soon after infection. We examine the role of Chlamydia and PID in EP using prospective evidence from the Lund study, evidence on the incidence and cumulative incidence of PID and EP in England, and retrospective evidence from case control studies. We assess the consistency of the data under different sets of assumptions about the severity of undiagnosed and non-hospital referred PID.Results If the risk of PID due to Chlamydia is constant over time then the probability that an untreated Chlamydia episode causes clinical PID is estimated to be about 15%, and there is approximately a 60% chance that annual testing would prevent an associated PID in a woman who becomes infected. If the PID rate is assumed to be higher for 1-3 months the respective figures are 16% and 50%. We estimate that between a third and a half of EPs are caused by PID. Of these, around a third are due to Chlamydia though estimates are highly uncertain. Our comparison of different data sources suggests that undiagnosed PID carries some risk of EP. Conclusions Our findings support a public health strategy that (a) identifies women with Chlamydia as soon after infection as possible i.e. to get tested on change of sexual partner; (b) has a low threshold for diagnosing and treating women with pelvic pain or suspected PID. Health Protection Agency, London, UKBackground Although the importance of age in the prevalence of Chlamydia is well recognised, its importance in the relationship between Chlamydia and pelvic inflammatory disease (PID) has received little attention in epidemiology. Methods We generate and compare several sets of estimates of the population attributable fraction (PAF) of PID due to chlamydia by age-group using a number of data sources. Estimates are obtained using data from case-control studies and Chlamydia population prevalence in England. A second set of estimates is obtained from data on the incidence of PID, the incidence of Chlamydia, and the risk that a Chlamydia infection causes PID. We estimate the incidence of all-cause PID by age in England from routine data sources, and evidence on the proportion of PID episodes that are diagnosed. We synthesise these data with data from the control arm of the POPI trial. We estimate Chlamydia incidence by age in a multiparameter evidence synthesis of studies of Chlamydia incidence, prevalence, and duration of infection. Finally we estimate the risk of PID following Chlamydia from a statistical synthesis of randomised controlled trials using a multistate model. A third estim...