Barriers to engagement with testing for sexually transmitted infections within a UK-based young adult Black Caribbean community: a qualitative study.

BACKGROUND: The Black Caribbean population have a disproportionately high burden of sexually transmitted infections (STIs) compared with other ethnic groups. The aim of this study was to explore barriers to engagement with STI testing within a UK-based young adult Black Caribbean community. METHODS: Semi-structured interviews were carried out with 14 young adults from the Black Caribbean community and six sexual healthcare professionals. Data were analysed thematically. A focus group of five young adults was conducted to refine themes. RESULTS: Data analysis generated three themes: (1) culturally embedded stigma; (2) historically embedded mistrust; and (3) lack of knowledge. Perceived as 'dirty', particularly for females, infection with STIs was stigmatised by religious conceptions of 'purity' and shame. This presented challenges in terms of cultural acceptability of talking about STI testing with partners, friends, and family. Legacies of colonialism, medical racism and malpractice compromised young people's trust in medical intervention and confidentiality of data management. A lack of knowledge related to STIs and their treatment, and in how to access and perform STI tests further served as a barrier. Culturally tailored interventions targeting these factors and delivered by radio, podcasts and social media were highlighted as having potential to improve engagement with STI testing. DISCUSSION: Engagement with STI testing by young adults from the Black Caribbean community is impacted by historically and culturally embedded teachings, practices and beliefs inherited through generations. Targeting these factors within culturally tailored interventions may be effective for increasing STI-testing, and thus reducing rates of STI-infection in this population.

Treatment of bacterial sexually transmitted infections in Europe: gonorrhoea, Mycoplasma genitalium, and syphilis.

This review explores the therapeutic challenges of sexually transmitted infections (STI) in Europe, which include increasing antimicrobial resistance and limited progress in drug discovery. We primarily focus on gonorrhoea, Mycoplasma genitalium, and syphilis infections. For gonorrhoea with escalating resistance rates we explore the possibility of combining ceftriaxone with another antibiotic or using alternative antibiotics to mitigate resistance emergence, and we provide insights on the ongoing evaluation of new antimicrobials, like gepotidacin and zoliflodacin. In the case of M. genitalium, which exhibits high resistance rates to first and second-line treatments, we emphasize the importance of resistance-guided therapy in regions with elevated resistance levels, and highlight the limited alternative options, such as pristinamycin and minocycline. Furthermore, we address the challenges posed by syphilis, where the primary treatment consists of penicillin or doxycycline, with challenges arising in neurosyphilis, allergy, pregnancy, and supply shortages and discuss the ongoing evaluation of alternative antimicrobials (e.g., ceftriaxone, cefixime, linezolid). Our findings identify priority actions and provide concrete solutions for long-term effective management of STIs and antimicrobial resistance mitigation.

Economic evaluation of antimicrobial resistance in curable sexually transmitted infections; a systematic review and a case study.

OBJECTIVE: To provide a summary of the economic and methodological evidence on capturing antimicrobial resistance (AMR) associated costs for curable sexually transmitted infections (STIs). To explore approaches for incorporating the cost of AMR within an economic model evaluating different treatment strategies for gonorrhoea, as a case study. METHODS: A systematic review protocol was registered on PROSPERO (CRD42022298232). MEDLINE, EMBASE, CINAHL, Cochrane Library, International Health Technology Assessment Database, National Health Service Economic Evaluation Database, and EconLit databases were searched up to August 2022. Included studies were analysed, quality assessed and findings synthesised narratively. Additionally, an economic evaluation which incorporated AMR was undertaken using a decision tree model and primary data from a randomised clinical trial comparing gentamicin therapy with standard treatment (ceftriaxone). AMR was incorporated into the evaluation using three approaches-integrating the additional costs of treating resistant infections, conducting a threshold analysis, and accounting for the societal cost of resistance for the antibiotic consumed. RESULTS: Twelve studies were included in the systematic review with the majority focussed on AMR in gonorrhoea. The cost of ceftriaxone resistant gonorrhoea and the cost of ceftriaxone sparing strategies were significant and related to the direct medical costs from persistent gonorrhoea infections, sequelae of untreated infections, gonorrhoea attributable-HIV transmission and AMR testing. However, AMR definition, the collection and incorporation of AMR associated costs, and the perspectives adopted were inconsistent or limited. Using the review findings, different approaches were explored for incorporating AMR into an economic evaluation comparing gentamicin to ceftriaxone for gonorrhoea treatment. Although the initial analysis showed that ceftriaxone was the cheaper treatment, gentamicin became cost-neutral if the clinical efficacy of ceftriaxone reduced from 98% to 92%. By incorporating societal costs of antibiotic use, gentamicin became cost-neutral if the cost of ceftriaxone treatment increased from £4.60 to £8.44 per patient. CONCLUSIONS: Inclusion of AMR into economic evaluations may substantially influence estimates of cost-effectiveness and affect subsequent treatment recommendations for gonorrhoea and other STIs. However, robust data on the cost of AMR and a standardised approach for conducting economic evaluations for STI treatment which incorporate AMR are lacking, and requires further developmental research.

Where do those experiencing sexual violence seek help and is routine enquiry acceptable within a sexual healthcare setting? Findings from a population-based survey.

OBJECTIVES: Most sexual violence (SV) remains undisclosed to healthcare professionals. The aims of this study were to identify where support would be sought after SV and whether routine enquiry about SV was acceptable in a sexual healthcare setting. DESIGN: An online population-based survey collected data on a history of SV and preferences on support after SV, in addition to sociodemographic data. Respondents' views on being routinely asked about SV were sought. SETTING AND PARTICIPANTS: This online survey was based in England, UK. There were 2007 respondents. RESULTS: The police were the most frequent first choice for support after experiencing SV (n=520; 25.9%); however, this was less common in individuals in younger age groups (p<0.001) and in those with a history of SV (17.2% vs 29.9%, p<0.001). For the 27.1% (532 of 1960) of respondents who reported a history of SV, the first choice of place for support was Rape Crisis or similar third-sector organisation. The majority of respondents supported routine enquiry about SV during Sexual and Reproductive Health Service (SRHS) consultations (84.4%), although acceptability was significantly lower in older age groups. CONCLUSIONS AND STUDY IMPLICATIONS: A greater awareness of the influence of sociodemographic factors, including ethnicity, age, gender, disability and a history of SV, when planning and delivering services for those who have experienced SV is needed. A history of SV is common in the general population, and a 'one-size-fits-all' approach to encourage disclosure and access to support is unlikely to be optimal. Routine enquiry about SV is highly acceptable in an SRHS setting and likely to improve disclosure when appropriately implemented.

Immune responses to Neisseria gonorrhoeae and implications for vaccine development.

Neisseria gonorrheoae is the causative agent of gonorrhea, a sexually transmitted infection responsible for a major burden of disease with a high global prevalence. Protective immunity to infection is often not observed in humans, possible due to high variability of key antigens, induction of blocking antibodies, or a large number of infections being relatively superficial and not inducing a strong immune response. N. gonorrhoeae is a strictly human pathogen, however, studies using mouse models provide useful insights into the immune response to gonorrhea. In mice, N. gonorrhoea appears to avoid a protective Th1 response by inducing a less protective Th17 response. In mouse models, candidate vaccines which provoke a Th1 response can accelerate the clearance of gonococcus from the mouse female genital tract. Human studies indicate that natural infection often induces a limited immune response, with modest antibody responses, which may correlate with the clinical severity of gonococcal disease. Studies of cytokine responses to gonococcal infection in humans provide conflicting evidence as to whether infection induces an IL-17 response. However, there is evidence for limited induction of protective immunity from a study of female sex workers in Kenya. A controlled human infection model (CHIM) has been used to examine the immune response to gonococcal infection in male volunteers, but has not to date demonstrated protection against re-infection. Correlates of protection for gonorrhea are lacking, which has hampered the progress towards developing a successful vaccine. However, the finding that the Neisseria meningitidis serogroup B vaccines, elicit cross-protection against gonorrhea has invigorated the gonococcal vaccine field. More studies of infection in humans, either natural infection or CHIM studies, are needed to understand better gonococcal protective immunity.

Intravaginal lactic acid gel versus oral metronidazole for treating women with recurrent bacterial vaginosis: the VITA randomised controlled trial.

BACKGROUND: Bacterial vaginosis is a common and distressing condition for women. Short-term antibiotic treatment is usually clinically effective, but recurrence is common. We assessed the effectiveness of intravaginal lactic acid gel versus oral metronidazole for treating recurrent bacterial vaginosis. METHODS: We undertook an open-label, multicentre, parallel group, randomised controlled trial in nineteen UK sexual health clinics and a university health centre. Women aged ≥ 16 years, with current bacterial vaginosis symptoms and a preceding history of bacterial vaginosis, were randomised in a 1:1 ratio using a web-based minimisation algorithm, to 400 mg twice daily oral metronidazole tablets or 5 ml once daily intravaginal lactic acid gel, for 7 days. Masking of participants was not possible. The primary outcome was participant-reported resolution of symptoms within 2 weeks. Secondary outcomes included time to first recurrence of symptoms, number of recurrences and repeat treatments over 6 months and side effects. RESULTS: Five hundred and eighteen participants were randomised before the trial was advised to stop recruiting by the Data Monitoring Committee. Primary outcome data were available for 79% (204/259) allocated to metronidazole and 79% (205/259) allocated to lactic acid gel. Resolution of bacterial vaginosis symptoms within 2 weeks was reported in 70% (143/204) receiving metronidazole versus 47% (97/205) receiving lactic acid gel (adjusted risk difference -23·2%; 95% confidence interval -32.3 to -14·0%). In those participants who had initial resolution and for whom 6 month data were available, 51 of 72 (71%) women in the metronidazole group and 32 of 46 women (70%) in the lactic acid gel group had recurrence of symptoms, with median times to first recurrence of 92 and 126 days, respectively. Reported side effects were more common following metronidazole than lactic acid gel (nausea 32% vs. 8%; taste changes 18% vs. 1%; diarrhoea 20% vs. 6%, respectively). CONCLUSIONS: Metronidazole was more effective than lactic acid gel for short-term resolution of bacterial vaginosis symptoms, but recurrence is common following both treatments. Lactic acid gel was associated with fewer reported side effects. TRIAL REGISTRATION: ISRCTN14161293 , prospectively registered on 18th September 2017.

STI testing and subsequent clinic attendance amongst test negative asymptomatic users of an internet STI testing service; one-year retrospective study.

AIM: To explore the characteristics of online STI test users, and assess the frequency and factors associated with subsequent service use following a negative online STI test screen in individuals without symptoms. METHODS: One-year retrospective study of online and clinic STI testing within a large integrated sexual health service (Umbrella in Birmingham and Solihull, England) between January and December 2017. A multivariable analysis of sociodemographic and behavioural characteristics of patients was conducted. Sexual health clinic appointments occurring within 90 days of a negative STI test, in asymptomatic individuals who tested either online or in clinic were determined. Factors associated with online STI testing and subsequent clinic use were determined using generalized estimating equations and reported as odds ratios (OR) with corresponding 95% confidence intervals (CI). RESULTS: 31 847 online STI test requests and 40 059 clinic attendances incorporating STI testing were included. 79% (25020/31846) of online STI test users and 49% (19672/40059) of clinic STI test takers were asymptomatic. Online STI testing was less utilised (p<0.05) by men who have sex with men (MSM), non-Caucasians and those living in neighborhoods of greater deprivation. Subsequent clinic appointments within 90 days of an asymptomatic negative STI test occurred in 6.2% (484/7769) of the online testing group and 33% (4960/15238) for the clinic tested group. Re-attendance following online testing was associated with being MSM (aOR 2.55[1.58 to 4.09]-MSM vs Female) and a recent prior history of STI testing (aOR 5.65[4.30 to 7.43] 'clinic tested' vs 'No' recent testing history). CONCLUSIONS: Subsequent clinic attendance amongst online STI test service users with negative test results was infrequent, suggesting that their needs were being met without placing an additional burden on clinic based services. However, unequal use of online services by different patient groups suggests that optimised messaging and the development of online services in partnership with users are required to improve uptake.

Providing a Supportive Environment for Disclosure of Sexual Violence and Abuse in a Sexual and Reproductive Healthcare Setting: A Realist Review.

Background: Sexual and reproductive healthcare services (SRHS) are an environment where medical care relevant to sexual violence and abuse (SV) is available. However, barriers to disclosure need to be overcome to allow timely access to this care. There is limited research identifying and explaining how interventions remove barriers and create a safe and supportive environment for disclosure. The purpose of this review was to develop and refine theories that explain how, for whom and in what context SRHS facilitate disclosure. Methods: Following published realist standards we undertook a realist review. After focussing the review question and identifying key contextual barriers, articles pertaining to these were identified using a traditional systematic database search. This strategy was supplemented with iterative searches. Results: Searches yielded 3172 citations, and 28 articles with sufficient information were included to develop the emerging theories. Four evidence-informed theories were developed proposing ways in which a safe and supportive environment for the disclosure of SV is enabled in SRHS. The theories consider how interventions may overcome barriers surrounding SV disclosure at individual, service-delivery and societal levels. Conclusions: Benefits of SRHS engagement with health promotion and health activism activities to address societal level barriers like lack of service awareness and stereotypic views on SV are presented. Although trauma informed practice and person-centred care were central in creating a safe and supportive environment for disclosure the review found them to be poorly defined in this setting.

Increasing attendance at pre-booked sexual health consultations: a systematic review.

BACKGROUND: Attending a sexual health consultation is integral to the effective prevention and treatment of sexually transmitted infections (STIs). However, individuals who may be at risk of STIs do not always do so, leading to an increased risk of STI complications and transmission of infection to others. This systematic review aimed to identify interventions implemented to increase attendance at a pre-booked sexual health clinic appointment and to identify behavioural theory and behaviour change techniques (BCTs), which form the basis for such interventions. METHODS: Articles were identified through a systematic search of four electronic databases (Web of Science; ProQuest; Scopus; PubMed) and included if they aimed to increase attendance at a pre-booked, synchronous sexual health consultation. The quality of included studies was assessed independently by two researchers. Findings were synthesised narratively. RESULTS: Thirteen studies were included from three countries; eight non-randomised before-after study designs and five randomised controlled trials. Behavioural interventions increased attendance at pre-booked sexual health consultations. Text messages were the most frequently used mode for intervention delivery. A total of 19 BCTs were identified, but only three studies mentioned behavioural theory. The most frequently used BCTs in effective interventions were: using credible sources, employing prompts/cues and the provision of information about health consequences. However, these BCTs were also identified in interventions that were not effective, meaning that optimal content and theoretical underpinning of effective interventions remains unclear. CONCLUSIONS: Behavioural interventions can increase attendance at sexual health consultations. Further research is needed to examine the effectiveness of different BCT combinations.

Sexual exposure and sexual behaviour in the interval between gonorrhoea treatment and test of cure: a cross-sectional cohort study.

OBJECTIVES: We explored sexual contact in the interval between the treatment for gonorrhoea and attending for a test of cure (ToC) and identified factors associated with sexual contact in this period. METHODS: Multivariable analysis of demographic, behavioural and clinical data with self-reported sexual contact prior to attending for a gonorrhoea ToC evaluation among participants recruited into the 'Gentamicin for the Treatment of Gonorrhoea' trial in England, between October 2014 and November 2016. Associations with sexual contact were expressed as prevalence ratios (PR) and their corresponding 95% CI. RESULTS: The median time to ToC was 15 days (interquartile range 14-20 days). 197/540 (37%) participants reported sexual contact in the time between treatment and ToC. Of these, 173/197 (88%) participants reported inconsistent condom use, including with previous partners (133/197 (68%)). A history of gonorrhoea (adjusted PR (aPR) 1.32 (1.03 to 1.69)) or syphilis (aPR 1.19 (1.08 to 1.32)), being in regular (aPR 1.71 (1.41 to 2.09)) sexual relationships, high number of partners in the last 3 months (aPR 1.77 (1.25 to 2.51))-'more than 5 partners' vs '0 to 1 partner', and attending for a ToC more than 14 days after treatment (aPR 1.40 (1.08 to 1. 81)) were associated with reporting sexual contact before the ToC appointment. However, age (aPR (1.00 (0.99 to 1.01)) and presenting with specific symptoms at baseline (aPR 1.17 (0.95 to 1.44)) were not associated with sexual contact by the ToC attendance. CONCLUSION: Sexual activity after receiving treatment for gonorrhoea and prior to a ToC evaluation was common. This was associated with previous infection history and specific behavioural characteristics. Knowledge of these factors can help guide safe sex counselling at the time of treatment.

The effect of intramuscular injection technique on injection associated pain; a systematic review and meta-analysis.

AIM: To review the effect of different intramuscular injection (IMI) techniques on injection associated pain, in adults. METHODS: The review protocol was registered on PROSPERO (CRD42019136097). MEDLINE, EMBASE, British Nursing Index and CINAHL were searched up to June 2020. Included studies were appraised and a meta-analysis, where appropriate, was conducted with a random effects model and test for heterogeneity. Standardised mean difference (SMD) with a 95% confidence interval in reported injection pain (intervention cf. control) was reported. RESULTS: 29 studies were included in the systematic review and 20 studies in the meta-analysis. 13 IMI techniques were identified. 10 studies applied local pressure to the injection site. Of these, applying manual pressure (4 studies, SMD = -0.85[-1.36,-0.33]) and Helfer (rhythmic) tapping (3 studies, SMD = -2.95[-5.51,-0.39]) to the injection site reduced injection pain, whereas the use of a plastic device to apply local pressure to the skin (ShotBlocker) did not significantly reduce pain (2 studies, SMD = -0.51[-1.58,0.56]). Acupressure techniques which mostly involved applying sustained pressure followed by intermittent pressure (tapping) to acupressure points local to the injection site reduced pain (4 studies: SMD = -1.62[-2.80,-0.44]), as did injections to the ventrogluteal site compared to the dorsogluteal site (2 studies, SMD = -0.43[-0.81,-0.06]). There was insufficient evidence on the benefits of the 'Z track technique' (2 studies, SMD = -0.20[-0.41,0.01]) and the cold needle technique (2 studies, SMD = -0.73[-1.83,0.37]) on injection pain. The effect of changing the needle after drawing up the injectate on injection pain was conflicting and warming the injectate did not reduce pain. Limitations included considerable heterogeneity, poor reporting of randomisation, and possible bias in outcome measures from unblinding of assessors or participants. CONCLUSIONS: Manual pressure or rhythmic tapping over the injection site and applying local pressure around the injection site reduced IMI pain. However, there was very high unexplained heterogeneity between studies and risk of significant bias within small studies.

Uptake and User Characteristics for Pharmacy-Based Contraception and Chlamydia Treatment: A Quantitative Retrospective Study from the UK.

The health provider Umbrella delivers several SRHS through more than 120 pharmacies in Birmingham (England). Umbrella pharmacy data collected between August 2015 and August 2018 were used to descriptively analyse the uptake and user characteristics for emergency contraception, short-acting oral contraception, condoms and chlamydia treatment. In total, 54,309 pharmacy visits were analysed. A total of 30,473 females presented for emergency contraception. Most were supplied with an emergency contraceptive pill (98.6%, 30,052 out of 30,473), which was levonorgestrel in 57.4% of cases (17,255 out of 30,052). Of those females who attended for short-acting oral contraception, 54.3% (1764 out of 3247) were provided with the progesterone-only pill. Of those who were given chlamydia treatment, the majority received doxycycline (76.8%, 454 out of 591). A total of 74% (14,888 out of 19,998) of those who requested condoms were not provided with specific instructions on their use. Pharmacies have the potential to make a substantial contribution to the delivery of an integrated sexual health service including rapid access to emergency contraception, convenient delivery of short-acting hormonal contraception and treatment of chlamydia. Appropriate education, support and audit is required to ensure the delivery of high-quality care.

Assessing the costs and outcomes of control programmes for sexually transmitted infections: a systematic review of economic evaluations.

OBJECTIVE: To identify economic evaluations of interventions to control STIs and HIV targeting young people, and to assess how costs and outcomes are measured in these studies. DESIGN: Systematic review. DATA SOURCES: Seven databases were searched (Medline (Ovid), EMBASE (Ovid), Web of Science, PsycINFO, NHS Economic Evaluation Database, NHS Health Technology Assessment and Database of Abstracts of Reviews of Effects) from January 1999 to April 2019. Key search terms were STIs (chlamydia, gonorrhoea, syphilis) and HIV, cost benefit, cost utility, economic evaluation, public health, screening, testing and control. REVIEW METHODS: Studies were included that measured costs and outcomes to inform an economic evaluation of any programme to control STIs and HIV targeting individuals predominantly below 30 years of age at risk of, or affected by, one or multiple STIs and/or HIV in Organisation for Economic Co-operation and Development countries. Data were extracted and tabulated and included study results and characteristics of economic evaluations. Study quality was assessed using the Philips and BMJ checklists. Results were synthesised narratively. RESULTS: 9530 records were screened and categorised. Of these, 31 were included for data extraction and critical appraisal. The majority of studies assessed the cost-effectiveness or cost-utility of screening interventions for chlamydia from a provider perspective. The main outcome measures were major outcomes averted and quality-adjusted life years. Studies evaluated direct medical costs, for example, programme costs and 11 included indirect costs, such as productivity losses. The study designs were predominantly model-based with significant heterogeneity between the models. DISCUSSION/CONCLUSION: None of the economic evaluations encompassed aspects of equity or context, which are highly relevant to sexual health decision-makers. The review demonstrated heterogeneity in approaches to evaluate costs and outcomes for STI/HIV control programmes. The low quality of available studies along with the limited focus, that is, almost all studies relate to chlamydia, highlight the need for high-quality economic evaluations to inform the commissioning of sexual health services.

Time to resolution of genital symptoms for uncomplicated gonorrhoea: a prospective cohort study.

OBJECTIVES: To determine the time to resolution of symptoms (TTR) following treatment of uncomplicated gonorrhoea and to identify factors associated with TTR in a cohort of sexual health clinic attendees. METHODS: Participants were recruited from 14 clinics across England into the 'Gentamicin for the Treatment of Gonorrhoea (GToG)' trial between October 2014 and November 2016. We analysed demographic, behavioural and clinical data in a subset of the GToG study cohort presenting with genital discharge and/or dysuria, who subsequently experienced microbiological clearance of Neisseria gonorrhoeae 2 weeks after treatment. Testing for gonorrhoea was performed using a nucleic acid amplification test. The results were expressed as median TTR (IQR) and HRs with 95% CIs for resolution of symptoms. RESULTS: 216 participants (89% male) with a mean age of 32 years reported genital discharge (204/216 (94%)) or dysuria (173/216 (80%)) at their baseline visit. Symptom resolution occurred in 202/216 (94%) at the 2-week follow-up appointment. The median TTR was 2 days (IQR 1-3 days). 50/216 (23%) patients presented with gonorrhoea-chlamydia coinfection at their baseline attendance and in this group symptom resolution was slower (3 days for gonorrhoea-chlamydia coinfection compared with 2 days for gonorrhoea only, HR 0.68 (95% CI 0.48 to 0.95)). TTR was also longer in women (4 days for females compared with 2 days for males, HR 0.47 (95% CI 0.29 to 0.77)). CONCLUSIONS: The time to resolution of genital symptoms following effective treatment of gonorrhoea is variable, but 90% of patients report symptom resolution within 1 week. Concurrent chlamydia infection and being female were associated with prolonged TTR.

Factors associated with severity and resolution of intramuscular injection site pain following treatment for uncomplicated gonorrhoea: a prospective cohort study of GToG trial participants.

Background:Intramuscular injection (IMI) pain reduces the acceptability of treatment, but data identifying those at highest risk of severe pain following an injection are limited. This study identified factors associated with the severity, duration and resolution of IMI pain following treatment for uncomplicated gonorrhoea. Methods: Data from a subset of participants (aged 16-70 years) recruited between October 2014 and November 2016 into the 'Gentamicin for the treatment of gonorrhoea' trial in England were analysed. Pain was measured using a visual analogue scale (VAS) immediately after injection. Self-reported duration of pain was collected at a scheduled 2-week follow-up visit. Results: Overall, 688 participants (82% male), reported a median pain VAS score of 23.5 (range 0-100), which was moderate-severe (VAS score >30) in 38% (262/688) of participants. Age [adjusted odds ratio (aOR) 0.86 per 5-yearly increase, (0.78-0.94)], gender [female cf. male, aOR 1.62 (1.18-2.24)], ethnicity [Asian cf. Caucasian, aOR 2.79 (1.72-4.51)], body mass index [aOR 0.80 per 5 kgm-2 increase, (0.72-0.89)] and antibiotic regimen [gentamicin cf. ceftriaxone, aOR 3.92, (3.12-4.93)] were associated with moderate-severe injection pain. The median duration of pain was 2 h (range 0-648). Gender [female cf. male, adjusted hazard ratio (aHR) 0.76 (0.57-1.00)], ethnicity [Mixed race cf. Caucasian, aHR 0.64 (0.45-0.92)], self-reported pain [aHR 0.97 per 10 mm VAS score increase, (0.95-0.99)] and symptom status [asymptomatic cf. symptomatic aHR 1.35 (1.12-1.64)] were associated with pain resolution. Conclusions: IMI pain is influenced by specific demographic, anthropometric and clinical factors. Knowledge of these factors will help identify those most at risk of pain.

How, why, for whom and in what context, do sexual health clinics provide an environment for safe and supported disclosure of sexual violence: protocol for a realist review.

INTRODUCTION: Supporting people subjected to sexual violence includes provision of sexual and reproductive healthcare. There is a need to ensure an environment for safe and supported disclosure of sexual violence in these clinical settings. The purpose of this research is to gain a deeper understanding of how, why, for whom and in what circumstances safe and supported disclosure occurs in sexual health services. METHODS AND ANALYSIS: To understand how safe and supported disclosure of sexual violence works within sexual health services a realist review will be undertaken with the following steps: (1) Focussing of the review including a scoping literature search and guidance from an advisory group. (2) Developing the initial programme theories and a search strategy using context-mechanism-outcome (CMO) configurations. (3) Selection, data extraction and appraisal based on relevance and rigour. (4) Data analysis and synthesis to further develop and refine programme theory, CMO configurations with consideration of middle-range and substantive theories. DATA ANALYSIS: A realist logic of analysis will be used to align data from each phase of the review, with CMO configurations being developed. Programme theories will be sought from the review that can be further tested in the field. ETHICS AND DISSEMINATION: This study has been approved by the ethics committee at University of Birmingham, and has Health Research Authority approval. Findings will be disseminated through knowledge exchange with stakeholders, publications in peer-reviewed journals, conference presentations and formal and informal reports. In addition, as part of a doctoral study, the findings will be tested in multisite case studies. PROSPERO REGISTRATION DETAILS: CRD4201912998. Dates of the planned realist review, from protocol design to completion, January 2019 to July 2020.

The frontiers of addressing antibiotic resistance in Neisseria gonorrhoeae.

The sexually transmitted infection gonorrhea, caused by the Gram-negative bacterium Neisseria gonorrhoeae, can cause urethritis, cervicitis, and systemic disease, among other manifestations. N. gonorrhoeae has rapidly rising incidence along with increasing levels of antibiotic resistance to a broad range of drugs including first-line treatments. The rise in resistance has led to fears of untreatable gonorrhea causing substantial disease globally. In this review, we will describe multiple approaches being undertaken to slow and control this spread of resistance. First, a number of old drugs have been repurposed and new drugs are being developed with activity against Neisseria gonorrhoeae. Second, vaccine development, long an important goal, is advancing. Third, new diagnostics promise rapid detection of antibiotic resistance and a shift from empiric to tailored treatment. The deployment of these new tools for addressing the challenge of antibiotic resistance will require careful consideration to provide optimal care for all patients while extending the lifespan of treatment regimens.

Factors associated with time to presentation for individuals with symptomatic uncomplicated genital gonorrhoea: a cross sectional cohort study of GToG trial participants.

OBJECTIVES: To determine the variation in the time from onset of symptoms to clinical presentation (time to presentation [TTP]) in a cohort of sexual health attendees with symptomatic uncomplicated genital gonorrhoea and to identify factors associated with TTP. METHODS: Participants were recruited from 14 clinics across England into the 'Gentamicin for the Treatment of Gonorrhoea (GToG)' trial between October 2014 and November 2016. Multivariable analysis was performed using prospectively collected demographic, behavioural and clinical data in a subset of the GToG study cohort presenting with genital discharge and/or dysuria who tested positive for Neisseria gonorrhoeae using a nucleic acid amplification test. The results were expressed as geometric mean ratios (GMR) with 95% CI for time to presentation after onset of symptoms. RESULTS: 316 participants (269 men and 47 women) with a median age of 27.6 years (IQR 23.0-34.8) were included. 194 (61%) were Caucasian, 29 (9%) Black African, 27 (9%) Asian and 66 (21%) of other ethnicities. Median TTP was 3 days for men (IQR 2-7) and 14 days for women (IQR 7-21). Participants reported genital discharge (297/316 [94%]), dysuria (251/316 [79%]), both genital discharge and dysuria (232/316 [73%]) and other concurrent symptoms 76/316 (24%) (e.g., rectal bleeding or genital itching). 45/316 (14%) participants reported sexual contact while symptomatic, of whom TTP was more than 7 days in 32/45 (71%). A longer TTP was associated with gender (female cf. male, GMR 2.34 [1.67 to 3.26]), no prior history of gonorrhoea (GMR 1.46 [1.15 to 1.86]), 'regular' or 'ex-regular' sexual relationship (regular cf. one off GMR 1.35 [1.05 to 1.72]); ex-regular cf. one off GMR 1.88 [1.12 to 3.14]), and being heterosexual (GMR 1.69 [1.31 to 2.19]). CONCLUSION: Specific demographic and behavioural factors are associated with a longer TTP in individuals with symptomatic genital gonorrhoea. Detailed knowledge of these factors can be used to prioritise and optimise gonorrhoea management and prevention.

Gentamicin, azithromycin and ceftriaxone in the treatment of gonorrhoea: the relationship between antibiotic MIC and clinical outcome.

OBJECTIVES: To investigate the relationship between MIC and clinical outcome in a randomized controlled trial that compared gentamicin 240 mg plus azithromycin 1 g with ceftriaxone 500 mg plus azithromycin 1 g. MIC analysis was performed on Neisseria gonorrhoeae isolates from all participants who were culture positive before they received treatment. METHODS: Viable gonococcal cultures were available from 279 participants, of whom 145 received ceftriaxone/azithromycin and 134 received gentamicin/azithromycin. Four participants (6 isolates) and 14 participants (17 isolates) did not clear infection in the ceftriaxone/azithromycin and gentamicin/azithromycin arms, respectively. MICs were determined by Etest on GC agar base with 1% Vitox. The geometric mean MICs of azithromycin, ceftriaxone and gentamicin were compared using logistic and linear regression according to treatment received and N. gonorrhoeae clearance. RESULTS: As the azithromycin MIC increased, gentamicin/azithromycin treatment was less effective than ceftriaxone/azithromycin at clearing N. gonorrhoeae. There was a higher geometric mean MIC of azithromycin for isolates from participants who had received gentamicin/azithromycin and did not clear infection compared with those who did clear infection [ratio 1.95 (95% CI 1.28-2.97)], but the use of categorical MIC breakpoints did not accurately predict the treatment response. The geometric mean MIC of azithromycin was higher in isolates from the pharynx compared with genital isolates. CONCLUSIONS: We found that categorical resistance to azithromycin or ceftriaxone in vitro, and higher gentamicin MICs in the absence of breakpoints, were poorly predictive of treatment failure.

Metronidazole versus lactic acid for treating bacterial vaginosis (VITA): protocol for a randomised controlled trial to assess the clinical and cost effectiveness of topical lactic acid gel for treating second and subsequent episodes of bacterial vaginosis.

BACKGROUND: Bacterial vaginosis (BV) affects 30-50% of women at some time in their lives and is an embarrassing and distressing condition which can be associated with potentially serious comorbidities. Current antibiotic treatments such as metronidazole are effective but can result in side effects, and recurrence is common. This trial aims to investigate whether lactic acid gel is clinically effective and cost effective in the treatment of recurrent BV compared with metronidazole. METHODS: VITA is an open-label, multicentre, parallel group randomised controlled trial for women with a clinical diagnosis of BV and at least one previous BV episode in the past 2 years. Participants will be randomised 1:1 to intravaginal lactic acid gel 5 ml once daily for 7 days or oral metronidazole tablets 400 mg twice daily for 7 days. All participants will be followed up for 6 months to assess health status and healthcare costs. A subgroup will be interviewed to further explore adherence, tolerability and acceptability of treatment. The estimated sample size is 1900 participants to detect a 6% absolute increase in response rate to 86% in those receiving lactic acid gel. The primary outcome is participant-reported resolution of BV at Week 2. DISCUSSION: Results from this trial will help inform UK treatment guidelines for BV and may provide an alternative effective treatment for recurrent episodes of this condition which avoids repeated exposure to antibiotics. TRIAL REGISTRATION: ISRCTN, ISRCTN14161293. Registered on 8 September 2017.