Sexually transmitted infections diagnosed in individuals presenting for forensic and medical care following sexual assault.

BACKGROUND: People who report sexual assault express concerns regarding contracting sexually transmitted infection (STI); however, published literature regarding the risk of STI transmission in this context is sparse. METHOD: We audited STI and blood-borne virus (BBV) testing at a forensic and medical sexual assault care service in the Australian Capital Territory between 2004 and 2022. Eligibility for testing among 1928 presentations was defined based on risk (eg, reported penetration). Testing at presentation included chlamydia and gonorrhoea 1850, syphilis and BBV 1472, and after 2-6 weeks, 890 out of 1928 (46.2%) and after 3 months 881 out of 1928 (45.7%), respectively. RESULTS: At presentation, 100 out of 1928 (5.2%) individuals were diagnosed with chlamydia, of those, 95 out of 1799 (5.3%) were female, and 5 out of 121 (4.1%) were male. Gonorrhoea was diagnosed in 7 out of 1920 (0.4%), 5 out of 95 female and 2 out of 5 male. Hepatitis B, which was all pre-existing, was diagnosed in 5 out of 1799 (0.3%). Overall, chlamydia prophylaxis was given to 203 out of 1928 (10.5%) and HIV post-exposure prophylaxis to 141 out of 1928 (7.3%).At 2-6 weeks of follow-up, 10 out of 890 (1.1%) individuals were diagnosed with chlamydia, with no gonorrhoea diagnosed. There were no cases of syphilis, hepatitis B or HIV diagnosed at 3-month serology testing in 881 individuals. Chlamydia detection at follow-up was more common in the group aged 15-29 years. Of those provided with chlamydia prophylaxis, 203 out of 1928, only 16 out of 203 (7.9%) were diagnosed with chlamydia. CONCLUSIONS: The offer of STI testing is almost universally accepted by individuals presenting for post-sexual assault care. There were no identifiable factors to justify the routine use of chlamydia prophylaxis. STI testing provided an opportunity for screening and should remain part of the clinical care of people who report sexual assault.

Characteristics of Human Immunodeficiency Virus (HIV) Seroconversions in a Large Prospective Implementation Cohort Study of Oral HIV Preexposure Prophylaxis in Men Who Have Sex with Men (EPIC-NSW).

BACKGROUND: Most human immunodeficiency virus (HIV) seroconversions in people who have initiated preexposure prophylaxis (PrEP) occur in the context of insufficient adherence. We describe participants who seroconverted after being dispensed PrEP in a large PrEP implementation study in Australia. METHODS: Expanded PrEP Implementation in Communities in New South Wales was an implementation study of daily oral PrEP in individuals aged ≥18 years at high risk for acquiring HIV. HIV seroconversions were defined as a positive HIV test by either antigen, antibody, or detectable HIV viral load after enrollment. Insufficient adherence, measured by dispensing logs or participant self-report, was defined as <4 PrEP doses per week. RESULTS: A total of 9596 participants were enrolled and dispensed PrEP between 1 March 2016 and 30 April 2018; 30 were diagnosed with HIV by 31 March 2019. The median (interquartile range [IQR]) age was 31 (25-38) years, all identified as male, 29 (97%) identified as gay or homosexual, and 20 (69%) lived in a postcode with a low concentration of gay male residents. The median (IQR) days from first PrEP dispensing to diagnosis was 409 (347-656). There was no evidence that participants who seroconverted had been sufficiently adherent to PrEP. Nineteen (63%) participants who seroconverted were diagnosed with chlamydia, gonorrhoea, syphilis, or new hepatitis C infection. One participant had resistance to emtricitabine (M184V mutation) at diagnosis. CONCLUSIONS: Participants who seroconverted were insufficiently adherent to PrEP despite being at high risk for acquiring HIV. Understanding the reasons for poor PrEP adherence in individuals who subsequently acquire HIV is critical to improving PrEP effectiveness.

Do we DARE? Improving digital ano-rectal examination in men who have sex with men living with HIV: a quality improvement initiative.

Men who have sex with men (MSM) living with HIV are at increased risk of anal cancer and annual screening via digital ano-rectal examination (DARE) is recommended. Baseline audit (Cycle 1) was undertaken of the medical records of MSM living with HIV aged ≥50years (n =85) from 1 January 2017 to 31 December 2018, in line with guidelines at the time. Data collection included whether DARE was discussed and offered, and whether DARE was accepted or declined. We provided staff training and altered clinic proformas aiming to increase DARE. Audit Cycle 2 (Cycle 2) was undertaken of eligible MSM (n =86) who attended between 1 January 2019 to 31 December 2020. DARE frequency increased from 4.7% in Cycle 1 to 41.8% in Cycle 2 (P <0.001) and discussion and offer of DARE increased from 8% to 64% in Cycle 2 (P <0.001).

Modelling the binding mode of macrocycles: Docking and conformational sampling.

Drug discovery is increasingly tackling challenging protein binding sites regarding molecular recognition and druggability, including shallow and solvent-exposed protein-protein interaction interfaces. Macrocycles are emerging as promising chemotypes to modulate such sites. Despite their chemical complexity, macrocycles comprise important drugs and offer advantages compared to non-cyclic analogs, hence the recent impetus in the medicinal chemistry of macrocycles. Elaboration of macrocycles, or constituent fragments, can strongly benefit from knowledge of their binding mode to a target. When such information from X-ray crystallography is elusive, computational docking can provide working models. However, few studies have explored docking protocols for macrocycles, since conventional docking methods struggle with the conformational complexity of macrocycles, and also potentially with the shallower topology of their binding sites. Indeed, macrocycle binding mode prediction with the mainstream docking software GOLD has hardly been explored. Here, we present an in-depth study of macrocycle docking with GOLD and the ChemPLP scores. First, we summarize the thorough curation of a test set of 41 protein-macrocycle X-ray structures, raising the issue of lattice contacts with such systems. Rigid docking of the known bioactive conformers was successful (three top ranked poses) for 92.7% of the systems, in absence of crystallographic waters. Thus, without conformational search issues, scoring performed well. However, docking success dropped to 29.3% with the GOLD built-in conformational search. Yet, the success rate doubled to 58.5% when GOLD was supplied with extensive conformer ensembles docked rigidly. The reasons for failure, sampling or scoring, were analyzed, exemplified with particular cases. Overall, binding mode prediction of macrocycles remains challenging, but can be much improved with tailored protocols. The analysis of the interplay between conformational sampling and docking will be relevant to the prospective modelling of macrocycles in general.

An observational study of the acceptability of patient-delivered partner therapy for management of chlamydia.

Partners of heterosexual cases with chlamydia, who were identified as having difficulty in attending the clinic, were offered patient-delivered partner therapy (PDPT). Medication was delivered by the index case after telephone consultation with the partner to assess symptoms and medical history. The opportunity for testing of partners for chlamydia was provided. The PDPT process was evaluated by standardised phone interview with index patients and partners. Telephone consultation enables safe medication prescribing and an opportunity for further contact tracing. Partners were unlikely to seek testing when provided with PDPT. Delivery of medication resulted in a reported rate of treatment of 100%. PDPT was an acceptable treatment option to both index and partner and should be considered if legislation permits.

A national study of the clinical management of HIV-positive women in Australia: what are the successes and where are the gaps?

Background Women comprise ~10% of people living with HIV in Australia, so are often underrepresented in research. METHODS: This study invited clinicians providing care to women living with HIV to complete an anonymous survey containing questions related to four key areas: HIV (including diagnosis, treatment and virological outcomes), reproductive health (including sexual activity, contraception, pregnancy and outcomes) and linkage and retention in care. RESULTS: In total, 484 surveys were received, with responses from all states and territories. Most women living with HIV in Australia are on treatment (>90%) and virologically suppressed (>90% have a viral load <50 copies mL-1). Almost 75% of women have had at least one switch in treatment (with toxicity almost as common as simplification as the indication). Treatment interruption is also relatively common, but is more likely the longer a woman has been diagnosed, if she is on benefits (P = 0.007) and is the primary carer of children without a partner (P = 0.001). In Australia, women living with HIV are a diverse heterogeneous group, with over 70 different countries of birth and almost half speaking a language other than English at home. Mental health diagnosis was the most common co-morbid condition identified. A total of 21% of women were post-menopausal, with 42% reporting symptoms to their healthcare provider, but only 17% were receiving treatment for symptoms attributed to menopause. CONCLUSIONS: As well as strategies to support women vulnerable to treatment interruption, important areas for future investment in research and clinical care include co-morbid mental health and menopause symptoms and treatment.

'Catching chlamydia': combining cash incentives and community pharmacy access for increased chlamydia screening, the view of young people.

In Australia and elsewhere, chlamydia screening rates for those aged between 16 and 30 years continue to be low. Innovative, age-appropriate approaches are necessary to increase chlamydia screening among this target group to prevent short- and long-term consequences of the infection such as pelvic inflammatory disease, chronic pelvic pain, ectopic pregnancy and infertility. Studies have demonstrated that offering chlamydia screening in community pharmacies may be a useful adjunct to current screening services. Approximately 90% of Australians visit a pharmacy at least once a year. Chlamydia screening and education in community pharmacies with remuneration may provide another option for opportunistic testing as part of a national chlamydia screening scheme. Compensation is an accepted practice in the field of research and has been demonstrated to improve adherence to health promotion activities. In 2011, a cross-sectional study of community pharmacy-based chlamydia screening offered in conjunction with an A$10 cash incentive to participate was conducted in the Australian Capital Territory. As part of this study young people were asked about their experience of, and views about, pharmacy-based chlamydia screening. The views of consented participants were collected using the one-page questionnaire consisting of 10 closed questions and one open-ended question. Participants completed the questionnaire when they returned their urine sample and before being given the cash incentive. Overall participants were highly satisfied with the pharmacy-based chlamydia screening service. Over 60% of questionnaire respondents felt that the payment did affect their decision to have the chlamydia test, and 23% stated that it made no difference. Young people reported that pharmacy-based screening is acceptable and convenient. Accessibility and the small cash incentive played significant roles in increasing participation.

Intergroup Contact Improves Medical Student Attitudes and Skill in Transgender Health Care.

Purpose: Poorer health outcomes for transgender and gender diverse (TGD) individuals have been associated with lack of health care provider knowledge and personal bias. Training at all levels of medical education has been positioned as one strategy to combat these inequities. This study sought to characterize preclinical medical student attitude, skill, and knowledge pre- and post-teaching with TGD community volunteers. Methods: This matched pre- and post-test study was conducted from July 2020 to August 2021 capturing two preclinical medical student cohorts exposed to the same teaching intervention. Students completed the Transgender Attitudes and Beliefs Scale (TABS) and the Transgender Development of Clinical Skills Scale (T-DOCSS) at baseline, 1 week, and 1 month after the clinical skills session. Tutors' attitudes to TGD health were measured before facilitating teaching, using the Attitudes Toward Transgender Patients and Beliefs and Knowledge about Treating Transgender Patients scales. Results: Fifty-nine students completed questionnaires at three time points and were included in this study. Total TABS and T-DOCCS scores increased from preintervention to 1-week follow-up, maintained at 1 month, with significant changes in Interpersonal Comfort and Sex and Gender Beliefs subscales. Scores on the Human Value subscale did not change, remaining consistently high. Postintervention knowledge-question scores were high. Nine of 13 tutors completed surveys, demonstrating overall positive attitudes toward gender diversity and TGD health. Conclusion: This study demonstrates improvement in preclinical medical student attitudes and self-reported skill toward gender health care sustained at 1 month after small-group teaching with TGD community volunteers.

Community pharmacy and cash reward: a winning combination for chlamydia screening?

OBJECTIVES: To date, the uptake of chlamydia screening in community pharmacies has been limited. The objective of this cross-sectional study was to determine if a cash reward, offered to both the provider and the consumer of chlamydia screening, increased the uptake of screening in community pharmacies. METHODS: During 4 weeks in 2011, chlamydia screening and education were offered in four city and two suburban pharmacies to people aged 16-30 years. Those who provided a urine sample for testing, contact details, and completed a brief questionnaire were rewarded with $A10. Positive participants, and their nominated contacts, were offered treatment. RESULTS: Over a period of 751.5 h, 979 testing kits were requested, and 900 (93%) urine samples returned. Using probabilistic linkage methods, we determined that 671/900 (75%) urine samples were from unique individuals. 0.9 unique samples were obtained/hour of screening, 63% of which were provided by men. 19/671 (2.8%; 95% CI 1.7% to 4.4%) people tested positive, 5.2% (95% CI 2.8% to 8.8%) of women, and 1.4% (1.4 0.5 to 3.1) of men. 11/19 (58%) people were contacted and treated-two for suspected pelvic inflammatory disease. CONCLUSIONS: Providing a cash reward to encourage chlamydia screening in community pharmacies resulted in greater participation rates than previously reported pharmacy-based studies, particularly among men. Easily implemented mechanisms to reduce inappropriate repeat screening, incorrect contact details and effects on pharmacy work flow may enhance the efficiency of this approach.

Cultivating intellectual community in academia: reflections from the Science and Technology Studies Food and Agriculture Network (STSFAN).

Scholarship flourishes in inclusive environments where open deliberations and generative feedback expand both individual and collective thinking. Many researchers, however, have limited access to such settings, and most conventional academic conferences fall short of promises to provide them. We have written this Field Report to share our methods for cultivating a vibrant intellectual community within the Science and Technology Studies Food and Agriculture Network (STSFAN). This is paired with insights from 21 network members on aspects that have allowed STSFAN to thrive, even amid a global pandemic. Our hope is that these insights will encourage others to cultivate their own intellectual communities, where they too can receive the support they need to deepen their scholarship and strengthen their intellectual relationships.

Is non-occupational HIV Post Exposure Prophylaxis (nPEP) still used? An exploration of nPEP use since widespread availability of HIV PrEP.

BACKGROUND: Non-occupational Post-Exposure Prophylaxis (nPEP) is an effective HIV prevention strategy in gay and bisexual men (GBM) taken after possible exposure. HIV Pre-Exposure Prophylaxis (PrEP) is also a highly effective HIV prevention strategy. METHODS: A retrospective audit of medical records of GBM presenting to a sexual health centre and provided with nPEP compared two periods to determine if nPEP usage changed following availability of PrEP. In the first period (P1) PrEP was available through extended trials. In the second period (P2) PrEP became more accessible through the Australian Pharmaceutical Benefits Scheme (PBS). Period comparisons were performed using a two-population test of proportions with one-tailed testing and significance set at P < .05 using SPSS Statistics Version 25. RESULTS: There were 232 GBM provided with nPEP in P1, and 202 in P2. A two-population test of proportions demonstrated that GBM presentations for nPEP decreased significantly from 302/4779 (6.3%) of GBM visits in P1 to 221/7205 (3.1%) in P2 when PrEP was more accessible (Z=8.53, P < .001). PrEP uptake after presenting for nPEP increased from 30 (12.9%) of total GBM visits in P1 to 69 (34.2%) in P2 (Z=5.26, p < .001). CONCLUSIONS: GBM accessing nPEP decreased with statistical significance post introduction of PBS PrEP.

FutureMS cohort profile: a Scottish multicentre inception cohort study of relapsing-remitting multiple sclerosis.

PURPOSE: Multiple sclerosis (MS) is an immune-mediated, neuroinflammatory disease of the central nervous system and in industrialised countries is the most common cause of progressive neurological disability in working age persons. While treatable, there is substantial interindividual heterogeneity in disease activity and response to treatment. Currently, the ability to predict at diagnosis who will have a benign, intermediate or aggressive disease course is very limited. There is, therefore, a need for integrated predictive tools to inform individualised treatment decision making. PARTICIPANTS: Established with the aim of addressing this need for individualised predictive tools, FutureMS is a nationally representative, prospective observational cohort study of 440 adults with a new diagnosis of relapsing-remitting MS living in Scotland at the time of diagnosis between May 2016 and March 2019. FINDINGS TO DATE: The study aims to explore the pathobiology and determinants of disease heterogeneity in MS and combines detailed clinical phenotyping with imaging, genetic and biomarker metrics of disease activity and progression. Recruitment, baseline assessment and follow-up at year 1 is complete. Here, we describe the cohort design and present a profile of the participants at baseline and 1 year of follow-up. FUTURE PLANS: A third follow-up wave for the cohort has recently begun at 5 years after first visit and a further wave of follow-up is funded for year 10. Longer-term follow-up is anticipated thereafter.

PrEP your team! Clinician initiation of HIV pre-exposure prophylaxis discussion at sexually transmissible infection testing and diagnosis in gay and bisexual men.

HIV pre-exposure prophylaxis (PrEP) is recommended for gay and bisexual men (GBM) with recent diagnosis of rectal chlamydia (CT), rectal gonorrhoea (NG) or infectious syphilis. A retrospective medical record audit was undertaken at Canberra Sexual Health Centre (CSHC) of all GBM who met this criterion in 2019 and were thus determined to be at higher risk of acquisition of human immunodeficiency virus (HIV). Pre-exposure prophylaxis was discussed and/or commenced in 85% of GBM at higher risk of HIV. Audit results and education were provided to the team with a post-interventional audit in 2020 showing significant improvement. This audit is easily replicated and may be applicable to other settings engaged in GBM care.

Primary invasive aspergillosis with disseminated intravascular coagulation as a presenting feature of non-Hodgkin's lymphoma.

Invasive aspergillosis (IA) is a life-threatening infection. IA is usually seen in severely immunocompromised patients. However, IA as a presenting feature of non-Hodgkin's lymphoma is rare. The patient we describe had no signs or symptoms of lymphoma prior to hospital admission. A. fumigatus was isolated from respiratory tract specimens on the day of admission and fungal elements were detected on autopsy. Isolation of Aspergillus in patients with severe sepsis should trigger a search haematological malignancy.

Can pharmacy assistants play a greater role in public health programs in community pharmacies? Lessons from a chlamydia screening study in Canberra, Australia.

BACKGROUND: Little is known about the engagement of pharmacy assistants (PA) in public health service provision. OBJECTIVE: To explore the experiences of PA participating in a study to determine whether a cash reward, offered to consumers and pharmacy businesses, increased participation in community pharmacy-based chlamydia screening. METHODS: PA experience of the study education and training package, participant recruitment and conducting screening (providing information about chlamydia, specimen collection and handling urine samples) were evaluated using knowledge assessment, a questionnaire and focus groups. RESULTS: Twenty PA participated in the study: 15 (75%) completed all education and training components, 20 (100%) completed the questionnaire and 10 (50%) attended a focus group. PA rated all education and training components as effective (mean visual analog scale scores >8.5). Most PA (13/18, 72.2%) did not support/were unsure about continuing the program, citing the 25% repeat testing rate (presumed to relate to the cash reward) and privacy/confidentiality issues as reasons. Qualitative analysis suggested that minimizing repeat testing, improved workload management and recognition of, and remuneration for, education and training would make this model more acceptable to PA. CONCLUSION: Findings from this study support the assertion that PA can play a significant role in public health initiatives.

[1,2,4]triazolo[4,3-a]phthalazines: inhibitors of diverse bromodomains.

Bromodomains are gaining increasing interest as drug targets. Commercially sourced and de novo synthesized substituted [1,2,4]triazolo[4,3-a]phthalazines are potent inhibitors of both the BET bromodomains such as BRD4 as well as bromodomains outside the BET family such as BRD9, CECR2, and CREBBP. This new series of compounds is the first example of submicromolar inhibitors of bromodomains outside the BET subfamily. Representative compounds are active in cells exhibiting potent cellular inhibition activity in a FRAP model of CREBBP and chromatin association. The compounds described are valuable starting points for discovery of selective bromodomain inhibitors and inhibitors with mixed bromodomain pharmacology.