Assessment of online self-testing and self-sampling service providers for sexually transmitted infections against national standards in the UK in 2020.

OBJECTIVES: Online testing for STIs may help overcome barriers of traditional face-to-face testing, such as stigma and inconvenience. However, regulation of these online tests is lacking, and the quality of services is variable, with potential short-term and long-term personal, clinical and public health implications. This study aimed to evaluate online self-testing and self-sampling service providers in the UK against national standards. METHODS: Providers of online STI tests (self-sampling and self-testing) in the UK were identified by an internet search of Google and Amazon (June 2020). Website information on tests and associated services was collected and further information was requested from providers via an online survey, sent twice (July 2020, April 2021). The information obtained was compared with British Association for Sexual Health and HIV and Faculty of Sexual and Reproductive Healthcare guidelines and standards for diagnostics and STI management. RESULTS: 31 providers were identified: 13 self-test, 18 self-sample and 2 laboratories that serviced multiple providers. Seven responded to the online survey. Many conflicts with national guidelines were identified, including: lack of health promotion information, lack of sexual history taking, use of tests licensed for professional-use only marketed for self-testing, inappropriate infections tested for, incorrect specimen type used and lack of advice for postdiagnosis management. CONCLUSIONS: Very few online providers met the national STI management standards assessed, and there is concern that this will also be the case for service provision aspects that were not covered by this study. For-profit providers were the least compliant, with concerning implications for patient care and public health. Regulatory change is urgently needed to ensure that all online providers are compliant with national guidelines to ensure high-quality patient care, and providers are held to account if non-compliant.

An economic evaluation of two PCR-based respiratory panel assays for patients admitted to hospital with community-acquired pneumonia (CAP) in the UK, France and Spain.

BACKGROUND: On admission to hospital, patients with community-acquired pneumonia (CAP), undergo extensive diagnostic testing. Two high-throughput laboratory-based PCR panels which return a result in 5.5 hours (h) have been developed to test for pathogens commonly associated with upper (Respiratory 1 Panel) and lower (Respiratory 3 Panel) respiratory tract infections (GeneFirst, Oxford). These could replace multiple diagnostic tests currently used. METHODS: An online survey, completed by senior clinicians in the UK, France and Spain, was used to collect data on the diagnostic testing of immunocompetent and immunocompromised adults admitted to hospital with CAP, including the cost of diagnostics. Data were used to inform a cost-comparison model. For each country, the average cost of diagnostic testing per patient was calculated separately for immunocompetent and immunocompromised patients. The model compared three testing strategies with standard of care (SoC). In the Panel 1 strategy, the Respiratory 1 Panel was used for patients that would otherwise have tests which could be replaced by Respiratory 1 Panel, equivalent strategies for Respiratory 3 Panel and for both panels combined were assessed. RESULTS: In total, 48 surveys were completed (UK = 17; France = 15; Spain = 16). Compared with SoC, the Panel 1 + 3 strategy was most favourable, resulting in cost savings for immunocompetent and immunocompromised patients respectively, of €22.09 (£18.50) and €26.12 (£21.88) in the UK, €99.60 and €108.77 in France and €27.07 and €51.87 in Spain. CONCLUSION: In all three countries, the use of these respiratory panels could reduce the average cost of diagnostics used for patients admitted to hospital with CAP.

Preferences for chlamydia testing and management in Hong Kong: a discrete choice experiment.

OBJECTIVES: As most chlamydia cases are asymptomatic, regular testing and timely management may be necessary for control. We aimed to determine the preferences of people living in Hong Kong for chlamydia testing and management services. METHODS: An online panel of sexually active individuals living in Hong Kong completed the survey with two discrete choice experiments (DCEs). The first DCE examined the preferred attributes of a chlamydia testing service (cost, location, appointment time, speed of results, delivery of results and availability of other STI testing). The second DCE examined the preferred attributes of a chlamydia management service (cost, access to patient-delivered partner therapy, location, travel time, type of person consulted and attitude of staff). RESULTS: In total, 520 individuals participated: average age 36.8 years (SD 9.9), 40% males and 66% had a bachelor's degree or higher. Choosing to test was most influenced by cost, followed by speed of results, delivery of results, extra STI testing, appointment available and the least important was the location of testing. Choosing to attend for management was most influenced by staff's attitude, followed by cost, who they consult, access to patient-delivered partner therapy, travel time and the least important was treatment location. CONCLUSION: To design effective chlamydia testing and management services, it is vital to respond to patient needs and preferences. For people living in Hong Kong, cost and staff attitude were the most important factors for deciding whether to test or be managed for chlamydia, respectively.

Modelling the effect of COVID-19 mass vaccination on acute hospital admissions.

BACKGROUND: Managing high levels of acute COVID-19 bed occupancy can affect the quality of care provided to both affected patients and those requiring other hospital services. Mass vaccination has offered a route to reduce societal restrictions while protecting hospitals from being overwhelmed. Yet, early in the mass vaccination effort, the possible impact on future bed pressures remained subject to considerable uncertainty. OBJECTIVE: The aim of this study was to model the effect of vaccination on projections of acute and intensive care bed demand within a 1 million resident healthcare system located in South West England. METHODS: An age-structured epidemiological model of the susceptible-exposed-infectious-recovered type was fitted to local data up to the time of the study, in early March 2021. Model parameters and vaccination scenarios were calibrated through a system-wide multidisciplinary working group, comprising public health intelligence specialists, healthcare planners, epidemiologists and academics. Scenarios assumed incremental relaxations to societal restrictions according to the envisaged UK Government timeline, with all restrictions to be removed by 21 June 2021. RESULTS: Achieving 95% vaccine uptake in adults by 31 July 2021 would not avert the third wave in autumn 2021 but would produce a median peak bed requirement ∼6% (IQR: 1-24%) of that experienced during the second wave (January 2021). A 2-month delay in vaccine rollout would lead to significantly higher peak bed occupancy, at 66% (11-146%) of that of the second wave. If only 75% uptake was achieved (the amount typically associated with vaccination campaigns), then the second wave peak for acute and intensive care beds would be exceeded by 4% and 19%, respectively, an amount which would seriously pressure hospital capacity. CONCLUSION: Modelling influenced decision-making among senior managers in setting COVID-19 bed capacity levels, as well as highlighting the importance of public health in promoting high vaccine uptake among the population. Forecast accuracy has since been supported by actual data collected following the analysis, with observed peak bed occupancy falling comfortably within the inter-quartile range of modelled projections.

Evidence of changing sexual behaviours and clinical attendance patterns, alongside increasing diagnoses of STIs in MSM and TPSM.

BACKGROUND: Due to rising numbers of STI diagnosis and increasing prevalence of antimicrobial resistance, we explored trends in STI testing frequency and diagnoses, alongside sexual decision making and attitudes concerning condom use and HIV pre-exposure prophylaxis (PrEP) at a large urban UK sexual health clinic. METHODS: We examined 66 528 electronic patient records covering 40 321 attendees between 2016 and 2019, 3977 of whom were men who have sex with men or trans persons who have sex with men (MSM/TPSM). We also explored responses from MSM/TPSM attendees sent an electronic questionnaire between November 2018 and 2019 (n=1975) examining behaviours/attitudes towards PrEP. We measured trends in STI diagnoses and sexual behaviours including condomless anal intercourse (CAI), using linear and logistic regression analyses. RESULTS: Tests resulting in gonorrhoea, chlamydia or syphilis diagnoses increased among MSM/TPSM from 13.5% to 18.5% between 2016 and 2019 (p<0.001). The average MSM/TPSM STI testing frequency increased from 1.5/person/year to 2.1/person/year (p=0.017). Gay MSM/TPSM had the highest proportions of attendances resulting in diagnoses, increasing from 15.1% to 19.6% between 2016 and 2019 (p<0.001) compared with bisexual/other MSM/TPSM increasing from 6.9% to 14.5% (p<0.001), alongside smaller but significant increases in non-MSM/TPSM from 5.9% to 7.7% (p<0.001).The proportion of MSM/TPSM clinic attendees reporting CAI in the previous 3 months prior to at least one appointment in a given year increased significantly from 40.6% to 45.5% between 2016 and 2019 (p<0.0001) and average number of partners from 3.8 to 4.5 (p=0.002). Of 617 eligible questionnaire responses, 339/578 (58.7%) HIV-negative and 29/39 (74.4%) HIV-positive MSM/TPSM indicated they would be more likely to have CAI with someone on PrEP versus not on PrEP. 358/578 (61.9%) HIV-negative respondents said that PrEP use would make them more likely to have CAI with HIV-negative partners. CONCLUSION: Rising numbers of STI diagnoses among MSM/TPSM are not attributable to increased testing alone. Increased CAI and number of partners may be attributable to evolving sexual decision making among PrEP users and their partners. Proportionally, bisexual/other MSM/TPSM have the steepest increase in STI diagnoses.

Human Immunodeficiency Virus Preexposure Prophylaxis Knowledge, Attitudes and Perceptions of Sexual Health Risk in an Age of Sexually Transmitted Infection Antimicrobial Resistance.

BACKGROUND: Human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP) has helped reduce new HIV infections. However, bacterial sexually transmitted infections (STIs) have increased among PrEP users. We examined PrEP knowledge, access, and risk perceptions in an age of antimicrobial resistance (AMR). METHODS: An online anonymous survey was distributed to all cisgender men/transpersons who have sex with men attending a sexual health clinic in Bristol, United Kingdom (October 2018 to November 2019). Interviews with a sample identified at increased risk of HIV were analyzed thematically and integrated with survey data. RESULTS: Five hundred and seventy-eight (95%) of 617 cisgender men/transpersons who have sex with men survey respondents were HIV-negative/unknown, of these, 202 (34.9%) had ever used PrEP. Interviewees (n = 24) reported widespread awareness of and enthusiasm for PrEP. Among nonusers, 39% (146/376) were unaware how to access PrEP, and 27% (103/376) could not access PrEP through the national "impact" trial of whom 79% (81/103) were eligible. The PrEP was described as "life-changing," but expense was the main barrier to use. Sixty-two percent (358/578) of HIV-negative/unknown respondents on PrEP were more likely to have condomless anal intercourse with someone they thought was HIV-negative. Interviewees used PrEP with other risk-reduction strategies. Sexually transmitted infections were seen as "curable" and AMR rarely influenced risk perception or sexual decision making. CONCLUSIONS: The PrEP awareness was high, but purchase cost limited access. PrEP may increase condomless anal intercourse, but interviewees used PrEP as one of many risk-reduction tools. Reduced fear of HIV transmission and testing was highly valued. Sexually transmitted infection AMR was not seen as an immediate threat and did not influence risk perception or sexual decision making.

Agent-based modelling study of antimicrobial-resistant Neisseria gonorrhoeae transmission in men who have sex with men: towards individualised diagnosis and treatment.

Background Antimicrobial-resistant (AMR) gonorrhoea is a global public health threat. Discriminatory point-of-care tests (POCT) to detect drug sensitivity are under development, enabling individualised resistance-guided therapy. METHODS: An individual-based dynamic transmission model of gonorrhoea infection in MSM living in London has been developed, incorporating ciprofloxacin-sensitive and resistant strains. The time-dependent sexual contact network is captured by periodically restructuring active connections to reflect the transience of contacts. Different strategies to improve treatment selection were explored, including discriminatory POCT and selecting partner treatment based on either the index case or partner susceptibility. Outcomes included population prevalence of gonorrhoea and drug dose counts. RESULTS: It is shown that using POCT to detect ciprofloxacin-sensitive infections could result in a large decrease in ceftriaxone doses (by 70% compared with the reference case in the simulations of this study). It also suggests that ceftriaxone use can be reduced with existing technologies, albeit to a lesser degree; either using index case sensitivity profiles to direct treatment of partners, or testing notified partners with strain discriminatory laboratory tests before treatment, reduced ceftriaxone use in our model (by 27% and 47% respectively). CONCLUSIONS: POCT to detect ciprofloxacin-sensitive gonorrhoea are likely to dramatically reduce reliance on ceftriaxone, but requires the implementation of new technology. In the meantime, the proportion of unnecessary ceftriaxone treatment by testing partners before treatment could be reduced significantly. Alternatively, index case sensitivity profiles could be used to select effective treatments for partners.

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.

Comparing the characteristics of users of an online service for STI self-sampling with clinic service users: a cross-sectional analysis.

OBJECTIVES: Online services for self-sampling at home could improve access to STI testing; however, little is known about those using this new modality of care. This study describes the characteristics of users of online services and compares them with users of clinic services. METHODS: We conducted a cross-sectional analysis of routinely collected data on STI testing activity from online and clinic sexual health services in Lambeth and Southwark between 1January 2016 and 31March 2016. Activity was included for chlamydia, gonorrhoea, HIV and syphilis testing for residents of the boroughs aged 16 years and older. Logistic regression models were used to explore potential associations between type of service use with age group, gender, ethnic group, sexual orientation, positivity and Index of Multiple Deprivation (IMD) quintiles. We used the same methods to explore potential associations between return of complete samples for testing with age group, gender, ethnic group, sexual orientation and IMD quintiles among online users. RESULTS: 6456 STI tests were carried out by residents in the boroughs. Of these, 3582 (55.5%) were performed using clinic services and 2874 (44.5%) using the online service. In multivariate analysis, online users were more likely than clinic users to be aged between 20 and 30 years, female, white British, homosexual or bisexual, test negative for chlamydia or gonorrhoea and live in less deprived areas. Of the individuals that ordered a kit from the online service, 72.5% returned sufficient samples. In multivariate analysis, returners were more likely than non-returners to be aged >20 years and white British. CONCLUSION: Nearly half (44.5%) of all basic STI testing was done online, although the characteristics of users of clinic and online services differed and positivity rates for those using the online service for testing were lower. Clinics remain an important point of access for some groups.

Cross-sectional study to evaluate Trichomonas vaginalis positivity in women tested for Neisseria gonorrhoeae and Chlamydia trachomatis, attending genitourinary medicine and primary care clinics in Bristol, South West England.

BACKGROUND: Highly sensitive, commercial nucleic acid amplification tests (NAAT) for Trichomonas vaginalis have only recently been recommended for use in the UK. While testing for T. vaginalis is routine in symptomatic women attending genitourinary medicine (GUM) clinics, it is rare in asymptomatic women or those attending primary care. The aim of this study was to evaluate the positivity of T. vaginalis using a commercial NAAT, in symptomatic and asymptomatic women undergoing testing for chlamydia and gonorrhoea in GUM and primary care settings. METHODS: Samples from 9186 women undergoing chlamydia and gonorrhoea testing in South West England between May 2013 and Jan 2015 were also tested for T. vaginalis by NAAT alongside existing tests. RESULTS: T. vaginalis positivity using NAAT was as follows: in GUM 4.5% (24/530, symptomatic) and 1.7% (27/1584, asymptomatic); in primary care 2.7% (94/3499, symptomatic) and 1.2% (41/3573, asymptomatic). Multivariable regression found that in GUM older age, black ethnicity and deprivation were independent risk factors for T. vaginalis infection. Older age and deprivation were also risk factors in primary care. Testing women presenting with symptoms in GUM and primary care using TV NAATs is estimated to cost £260 per positive case diagnosed compared with £716 using current microbiological tests. CONCLUSIONS: Aptima TV outperforms existing testing methods used to identify T. vaginalis infection in this population. An NAAT should be used when testing for T. vaginalis in women who present for testing with symptoms in primary care and GUM, based on test performance and cost.

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.

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.

An economic evaluation of two cervical screening algorithms in Belgium: HR-HPV primary compared to HR-HPV and liquid-based cytology co-testing.

OBJECTIVE: To assess the costs and benefits of two algorithms for cervical cancer screening in Belgium (1) high-risk human papillomavirus (HR-HPV) primary screening and (2) HR-HPV and liquid-based cytology (LBC) co-testing. METHODS: A decision tree was adapted from published work and parameterised using HORIZON study data and Belgian cost and population data. The theoretical model represents two different screening algorithms for a cohort of 577 846 women aged 25-64 attending routine cervical screening. Scenario analyses were used to explore the impact of including vaccinated women and alternative pricing approaches. Uncertainty analyses were conducted. RESULTS: The cost per woman screened was €113.50 for HR-HPV primary screening and €101.70 for co-testing, representing a total cost of €65 588 573 and €58 775 083, respectively, for the cohort; a 10% difference. For one screening cycle, compared to HR-HPV primary, co-testing resulted in 13 173 more colposcopies, 67 731 more HR-HPV tests and 477 020 more LBC tests. Co-testing identified 2351 more CIN2+ cases per year (27% more than HR-HPV primary) and 1602 more CIN3+ cases (24% more than HR-HPV primary) than HR-HPV primary. CONCLUSION: In Belgium, a co-testing algorithm could increase cervical pre-cancer detection rates compared to HR-HPV primary. Co-testing would cost less than HR-HPV primary if the cost of the HPV test and LBC were cost-neutral compared to the current cost of LBC screening but would cost more if the cost per HPV test and LBC were the same in both co-testing and HR-HPV primary strategies.

Multiple Streptococcus pneumoniae serotypes in aural discharge samples from children with acute otitis media with spontaneous otorrhea.

Among 55 children with cultures positive for acute otitis media with spontaneous otorrhea, 28 (51%) had cultures positive for aural Streptococcus pneumoniae, and in 10 of these, two distinct strains were detected, in which 5 had pairs of strains that were both capsule-bearing serotypes. Such cases were more likely to have cultures positive for other otopathogens than those with only one pneumococcus present.

Chlamydia screening, retesting and repeat diagnoses in Cornwall, UK 2003-2009.

OBJECTIVES: This study aims to describe the patterns of testing and retesting for chlamydia in Cornwall during the first 5 years of the National Chlamydia Screening Programme. We evaluate the factors associated with retesting and estimate the incidence of chlamydia diagnosis and repeat diagnosis. STUDY DESIGN: Secondary database analysis. SELECTION CRITERIA: men and women tested for chlamydia between March 2003 and January 2009 in Cornwall, aged ≥12 years and ≤25 years at the first test. The factors associated with retesting in those with at least one known test result and at least 14 days follow-up time were analysed using Cox regression and the incidence of diagnosis and repeat diagnosis were calculated. RESULTS: The final dataset consisted of 71 066 records from 49 941 individuals; of whom 59.0% were female and 75.4% were only tested once. There were 48 375 individuals with at least one known test result (negative or positive) and at least 14 days follow-up, included in the Cox regression analysis. Factors associated with testing more than once were (adjusted HR, 95% CI): being female (2.24; 2.14 to 2.34) and initially testing positive (1.43; 1.35 to 1.51). The positivity at first episode declined from 13.2% (1077 cases) in 2003/2004 to 5.8% (843 cases) in 2008/2009. The incidence of diagnosis at the second test was 5.9 per 100 person years in those testing negative at the first test compared with 18.1 per 100 person years in those initially positive. DISCUSSION: Most individuals in this analysis were tested only once, but the testing volume and proportion of repeat tests were highest at the end of the study period. As the testing rate stabilises to 30% coverage, maintaining retesting rates in those previously tested and especially in those previously diagnosed with chlamydia will be necessary for the sustainability of the screening programme. CONCLUSIONS: A key feature of the next 5 years of the screening programme will be to maintain screening and rescreening.

Comparing the Costs and Diagnostic Outcomes of Replacing Cytology with the QIAsure DNA Methylation Test as a Triage within HPV Primary Cervical Cancer Screening in The Netherlands.

Detecting hypermethylation of tumour suppressor genes could provide an alternative to liquid-based cytology (LBC) triage within HPV primary cervical screening. The impact of using the QIAsure® FAM19A4/mir124-2 DNA Methylation Test (QIAGEN, N.V, Hilden, Germany) on CIN3+ diagnoses, retention, unnecessary colposcopies, and programme costs is unknown. A decision-tree model was developed to compare LBC with the QIAsure Methylation testing to guide colposcopy referral. Incorporating clinician- and self-sampling pathways the model was informed by the Dutch cervical cancer screening programme, published studies, and manufacturer data. Clinical and cost outcomes were assessed using two scenarios for DNA methylation testing and LBC relative performance. Sensitivity analyses (deterministic and probabilistic) were performed to assess model and parameter uncertainty. A range of self-sampling uptake was assessed in scenario analyses. For the screening cohort (n = 807,269) where 22.1% self-sampled, the number of unnecessary colposcopies and CIN3+ diagnoses varied according to the relative performance of methylation testing and LBC. Irrespective of relative performance, the cost per complete screen was lower and fewer people were lost to follow-up when using DNA methylation testing. The results indicate that, within an HPV primary screening programme that incorporates self-sampling, using the QIAsure Methylation Test for triage reduces the cost per screen compared to LBC.

Estimating the Health and Economic Impact of Improved Management in Prevalent Chronic Obstructive Pulmonary Disease Populations in England, Germany, Canada, and Japan: A Modelling Study.

Introduction: COPD is a leading cause of morbidity and mortality globally. Management is complex and costly. Although international quality standards for diagnosis and management exist, opportunities remain to improve outcomes, especially in reducing avoidable hospitalisations. Objective: To estimate the potential health and economic impact of improved adherence to guideline-recommended care for prevalent, on-treatment COPD populations in four high-income settings. Methods: A disease simulation model was developed to evaluate the impact of theoretical improvements to COPD management, comparing outcomes for usual care and policy scenarios for interventions that reduce avoidable hospitalisations: 1) increased attendance (50% vs 31-38%) of early follow-up review after severe exacerbation hospitalisation; 2) increased access (30% vs 5-10%) to an integrated disease management (IDM) programme that provides guideline adherent care. Results: For cohorts of 100,000 patients, Policy 1 yielded additional life years (England: 523; Germany: 759; Canada: 1316; Japan: 512) and lifetime cost savings (-£2.89 million; -€6.58 million; -$40.08 million; -¥735.58 million). For Policy 2, additional life years (2299; 3619; 3656) and higher lifetime total costs (£38.15 million; €35.58 million; ¥1091.53 million) were estimated in England, Germany and Japan, and additional life years (4299) and cost savings (-$20.52 million) in Canada. Scenarios found that the cost impact depended on the modelled intervention effect size. Conclusion: Interventions that reduce avoidable hospitalisations are estimated to improve survival and may generate cost savings. This study provides evidence on the theoretical impact of policies to improve COPD care and highlights priority areas for further research to support evidence-based policy decisions.

Evidence that faecal carriage of resistant Escherichia coli by 16-week-old dogs in the United Kingdom is associated with raw feeding.

We report a survey (August 2017 to March 2018) and risk factor analysis of faecal carriage of antibacterial-resistant (ABR) Escherichia coli in 223 16-week-old dogs in the United Kingdom. Raw feeding was associated with the presence of fluoroquinolone-resistant (FQ-R) E. coli and those resistant to tetracycline, amoxicillin, and streptomycin, but not to cefalexin. Whole genome sequencing of 36 FQ-R E. coli isolates showed a wide range of sequence types (STs), with almost exclusively mutational FQ-R dominated by ST744 and ST162. Comparisons between E. coli isolates from puppies known to be located within a 50 × 50 km region with those isolated from human urinary tract infections (isolated in parallel in the same region) identified an ST744 FQ-R lineage that was carried by one puppy and caused one urinary tract infection. Accordingly, we conclude that raw feeding is associated with carriage of ABR E. coli in dogs even at 16 weeks of age and that bacteria carried by puppies are shared with humans. We therefore suggest that those who feed their dogs raw meat seriously consider the potential ABR-transmission threat their pet may become as a result and deploy appropriate hygiene practices in mitigation.

Effectiveness of a behavioural intervention delivered by text messages (safetxt) on sexually transmitted reinfections in people aged 16-24 years: randomised controlled trial.

OBJECTIVE: To quantify the effects of a series of text messages (safetxt) delivered in the community on incidence of chlamydia and gonorrhoea reinfection at one year in people aged 16-24 years. DESIGN: Parallel group randomised controlled trial. SETTING: 92 sexual health clinics in the United Kingdom. PARTICIPANTS: People aged 16-24 years with a diagnosis of, or treatment for, chlamydia, gonorrhoea, or non-specific urethritis in the past two weeks who owned a mobile phone. INTERVENTIONS: 3123 participants assigned to the safetxt intervention received a series of text messages to improve sex behaviours: four texts daily for days 1-3, one or two daily for days 4-28, two or three weekly for month 2, and 2-5 monthly for months 3-12. 3125 control participants received a monthly text message for one year asking for any change to postal or email address. It was hypothesised that safetxt would reduce the risk of chlamydia and gonorrhoea reinfection at one year by improving three key safer sex behaviours: partner notification at one month, condom use, and sexually transmitted infection testing before unprotected sex with a new partner. Care providers and outcome assessors were blind to allocation. MAIN OUTCOME MEASURES: The primary outcome was the cumulative incidence of chlamydia or gonorrhoea reinfection at one year, assessed by nucleic acid amplification tests. Safety outcomes were self-reported road traffic incidents and partner violence. All analyses were by intention to treat. RESULTS: 6248 of 20 476 people assessed for eligibility between 1 April 2016 and 23 November 2018 were randomised. Primary outcome data were available for 4675/6248 (74.8%). At one year, the cumulative incidence of chlamydia or gonorrhoea reinfection was 22.2% (693/3123) in the safetxt arm versus 20.3% (633/3125) in the control arm (odds ratio 1.13, 95% confidence interval 0.98 to 1.31). The number needed to harm was 64 (95% confidence interval number needed to benefit 334 to ∞ to number needed to harm 24) The risk of road traffic incidents and partner violence was similar between the groups. CONCLUSIONS: The safetxt intervention did not reduce chlamydia and gonorrhoea reinfections at one year in people aged 16-24 years. More reinfections occurred in the safetxt group. The results highlight the need for rigorous evaluation of health communication interventions. TRIAL REGISTRATION: ISRCTN registry ISRCTN64390461.