Client and staff perceptions of acceptability of MyCheck: a direct-to-pathology telehealth and e-testing service for comprehensive bloodborne virus and sexually transmissible infection screening.

Background Sydney Sexual Health Centre (SSHC) is the largest sexual health clinic in New South Wales (NSW), servicing clients at high risk of sexually transmissible infections and bloodborne viruses. SSHC piloted a direct-to-pathology pathway that facilitated bloodborne virus/sexually transmissible infection testing at one of the ~500 participating pathology collection centres located across NSW. This qualitative study sought to understand SSHC client and provider perspectives of acceptability of the MyCheck intervention. Methods Semi-structured in-depth interviews were conducted with 11 clients who underwent testing via the MyCheck pathway and eight staff members involved in implementing MyCheck. The seven components of Sekhon's Theoretical Framework of Acceptability informed this analysis. Results Participants broadly conveyed 'affective attitude' toward the MyCheck pathway. The telehealth intervention reduced client 'burden' and 'opportunity cost' through enabling greater testing convenience at a location suitable to them and provided timely results. Issues of 'ethicality' were raised by clients and staff as pathology centre staff were, on a few occasions, regarded as being judgmental of SSHC clients. 'Intervention coherence' issues were largely attributed to pathology centre personnel being unfamiliar with the intervention, with billing issues being a recurrent concern. Participants perceived MyCheck as an 'effective' testing pathway. SSHC staff were able to offer the intervention with ease through seamless IT integration ('self-efficacy'). Conclusion The MyCheck intervention was perceived by both SSHC clients and staff as an acceptable bloodborne virus/sexually transmissible infection testing pathway. However, further work is required to address stigma experienced by some clients when attending pathology collection centres.

Non-empirical management of asymptomatic chlamydia and gonorrhoea reduces unnecessary antibiotic use fivefold: a before and after study.

OBJECTIVES: In 2019, informed by favourable patient and provider acceptability surveys and concerns about antimicrobial resistance, Sydney Sexual Health Centre stopped routinely providing empirical antibiotic treatment to asymptomatic contacts of Chlamydia trachomatis (chlamydia) and Neisseria gonorrhoea (gonorrhoea). We aimed to assess if this policy change had any negative impact on patient outcomes. METHODS: A retrospective file review of people who presented as asymptomatic contacts of chlamydia and gonorrhoea cases before and after the policy change was conducted. Data on infection type, test results and treatment were extracted. For contacts who tested positive and were treated non-empirically, additional data were reviewed including sexual activity and symptom or complication development between testing and treatment, time from testing to notification and treatment and loss to follow-up. RESULTS: Of 1194 asymptomatic sexual contacts of chlamydia or gonorrhoea, most tested negative to both infections (814, 68%). All contacts with a positive result who were not treated empirically were notified of their result and 173 (99%) were treated within a mean time of 5 days. More contacts were overtreated in 2018 (n=355, 58%) under the empirical treatment model compared with 2019 (n=58, 11%, p≤0.001). There was no significant difference in the proportion of contacts who tested positive and were treated (p=0.111) or developed symptoms (p=0.413) before and after the policy change and no contacts who were treated non-empirically developed complications of pelvic inflammatory disease, epididymitis or proctitis between testing and treatment. CONCLUSION: In this population, a switch from empirically treating all asymptomatic contacts to treating only those who tested positive significantly reduced antibiotic overuse with minimal adverse outcomes. Our findings support results-directed treatment for asymptomatic sexual contacts of chlamydia and gonorrhoea.

Real-world trends in incidence of bacterial sexually transmissible infections among gay and bisexual men using HIV pre-exposure prophylaxis (PrEP) in Australia following nationwide PrEP implementation: an analysis of sentinel surveillance data.

BACKGROUND: Although data from large implementation trials suggest that sexually transmissible infection (STI) risk increases among gay and bisexual men who initiate HIV pre-exposure prophylaxis (PrEP), there are few data on the trends in population-level STI incidence in the years following widespread PrEP implementation. We aimed to describe trends in bacterial STI incidence among gay and bisexual men using PrEP across Australia in the context of broad PrEP availability through Australia's subsidised medicines scheme. METHODS: We analysed linked clinical data from HIV-negative gay and bisexual men aged 16 years or older who had been prescribed PrEP across a sentinel surveillance clinical network, including 37 clinics in Australia, between Jan 1, 2016, and Dec 31, 2019. Patients were included if they had STI testing at least twice during the observation period. Repeat testing methods were used to calculate chlamydia, gonorrhoea, syphilis, and any STI incidence rates during individuals' periods of PrEP use. Incidence rate ratios (IRRs) for estimated change in incidence per half calendar year (6-month) period were calculated using negative binomial regression. Secondary analyses compared STI incidence rates across individuals initiating PrEP in each year from 2016 to 2019, as well as by length of time using PrEP (per each additional 6 months of PrEP use). FINDINGS: 22 730 men were included in the analyses. During the observation period, 11 351 chlamydia infections were diagnosed in 6630 (30·1%) of 22 034 men over 25 991·2 person-years of PrEP use (incidence rate 43·7 cases [95% CI 42·9-44·5] per 100 person-years). Chlamydia incidence decreased from 48·7 cases per 100 person-years in July-December, 2016, to 42·0 cases per 100 person-years in July-December, 2019 (IRR for estimated change per 6-month period 0·98 [95% CI 0·97-0·99]; p=0·0031). 9391 gonorrhoea infections were diagnosed in 5885 (26·9%) of 21 845 men over 24 858·7 person-years of PrEP use (incidence rate 37·8 cases [95% CI 37·0-38·5] per 100 person-years). Gonorrhoea incidence decreased from 45·5 cases per 100 person-years in July-December, 2016, to 37·2 cases per 100 person-years in July-December, 2019 (IRR 0·97 [95% CI 0·96-0·98]; p<0·0001). Declines in chlamydia and gonorrhoea incidence were most prominent in the first 18 months of observation and incidence was stable thereafter. 2062 syphilis infections were diagnosed in 1488 (7·7%) of 19 262 men over 21 978·9 person-years of PrEP use (incidence rate 9·4 cases [95% CI 9·0-9·8] per 100 person-years). Syphilis incidence increased from 6·2 cases per 100 person-years in July-December, 2016, to 9·8 cases per 100 person-years in July-December, 2019 (IRR 1·08 [95% CI 1·05-1·10]; p<0·0001). INTERPRETATION: Chlamydia and gonorrhoea incidence among gay and bisexual men using PrEP were highest in the early months of PrEP implementation in Australia and stabilised at slightly lower rates thereafter following wider PrEP uptake. Lower prospective STI risk among people initiating PrEP in later years contributed to the observed trends in STI incidence. Widespread PrEP implementation can contribute to increased STI screening and detection. FUNDING: Australian Department of Health, National Health and Medical Research Council.

Low Awareness of Mycoplasma genitalium in Men Who Have Sex With Men in Sydney, Australia.

OBJECTIVES: Mycoplasma genitalium (M. genitalium) is a sexually transmitted infection of importance because of the high prevalence rates and antimicrobial resistance (AMR) among men who have sex with men (MSM). METHODS: A prospective cross-sectional analysis was carried out on MSM who presented rectally asymptomatic at a central Sydney sexual health clinic or a community site for routine testing. Between March and May 2017, participants were asked to complete a questionnaire before testing. We used multivariable logistic regression to identify factors associated with awareness and concern toward M. genitalium and AMR. RESULTS: Overall, 692 (92.5%) of 746 (95% confidence interval [CI], 90.7-94.5) MSM had no prior awareness of M. genitalium; 512 (68.6%) of 746 (95% CI, 65.2-72.0) were not concerned or were neutral about the infection; and 234 (31.4%) of 746 (95% CI, 28.0-34.8) were a little, somewhat, or very concerned. High partner numbers (adjusted odds ratio [AOR], 4.2; 95% CI, 2.1-8.2) and inconsistent condom users (AOR, 3.1; 95% CI, 1.2-8.2) and no condoms used (AOR, 3.9; 95% CI, 1.2-12.6) were associated with awareness of the infection. Time since arrival in Australia of more than 10 years (AOR, 1.73; 95% CI, 1.09-2.75), more than 12 months (AOR, 1.91; 95% CI, 1.31-2.79), and recreational drug use (AOR, 1.95; 95% CI, 1.17-3.24) were associated with concern around having M. genitalium. Overall, 61.6% (458/744; 95% CI, 58.2-65.3) MSM reported that they would increase condom use (38.6% agreed and 23.1% strongly agreed) after reading about AMR. Among the remaining 38.4% (286/744), 28.4% indicated a neutral response to increasing their condom use. Relative to MSM born in Australia, Latin American (AOR, 7.3; 95% CI, 2.9-18.4) or Asian MSM (AOR, 2.3; 95% CI, 1.4-3.3), were significantly more likely to increase condom use after reading a statement on AMR. CONCLUSIONS: Knowledge of M. genitalium remains low among MSM. Targeted messages using AMR and treatment difficulties with M. genitalium is unlikely to change behavior for a large proportion of MSM.

Ask Dr Google: what STI do I have?

OBJECTIVES: Between 2013 and 2014, a third of Australian adults reported using the internet to investigate medical symptoms before consulting a medical practitioner. However, there is limited evidence regarding internet health information seeking behaviour (HISB) in sexual health. This study aims to determine the frequency, predictors and accuracy of internet HISB for sexual health self-diagnosis. METHODS: A cross-sectional paper-based survey, available in English, Chinese and Thai, was conducted during April to August 2019 at the Sydney Sexual Health Centre (SSHC). Symptomatic patients were recruited to answer an 18-item survey on their HISB, self-assessed diagnosis, anxiety and health literacy. Survey responses were correlated with SSHC electronic medical record data including participant demographics and clinician diagnosis. Data analyses were performed using Stata V.14. RESULTS: The majority of participants searched the internet (355; 79.1%) before attending clinic, and of these only 16.9% made a correct self-diagnosis. Multivariate analyses demonstrated that relative to Australian-born participants, people born in Asia were twice as likely to undertake internet HISB (adjusted OR (AOR) 2.41, 95% CI 1.25 to 4.64, p<0.01), and those born in Latin America were more likely to self-diagnose correctly (AOR 3.35, 95% CI 1.20 to 9.37, p<0.01). On average, participants who searched the internet scored higher relative to those who did not search, on measures of feeling generally tense (2.26, 95% CI 2.16 to 2.7 and 1.86, 95% CI 1.67 to 2.05, p<0.001), upset (1.96, 95% CI 1.85 to 2.08 and 1.53, 95% CI 1.35 to 1.72, p<0.001) and worried (2.55, 95% CI 2.44 to 2.65, and 2.16, 95% CI 1.95 to 2.38, p=0.001). CONCLUSIONS: This study has filled important gaps in the literature and highlighted the high prevalence of adults engaging in HISB for sexual health information. Of concern are the increased levels of anxiety and low accuracy of self-diagnoses associated with HISB. Strategies to direct patients to reputable and user-friendly health websites that mitigate anxiety and misinterpretation of online health information should be explored.

Changing the Use of HIV Pre-exposure Prophylaxis Among Men Who Have Sex With Men During the COVID-19 Pandemic in Melbourne, Australia.

We surveyed 204 men who have sex with men (MSM) who were pre-exposure prophylaxis (PrEP) users. One in 4 daily PrEP users stopped taking PrEP during the COVID-19 pandemic, and 5% switched to on-demand PrEP. Most men reduced PrEP use because they stopped having casual sex and reduced the number of casual partners during the COVID-19 pandemic.

Increases in HIV Testing Frequency in Australian Gay and Bisexual Men are Concentrated Among PrEP Users: An Analysis of Australian Behavioural Surveillance Data, 2013-2018.

Increasing HIV testing frequency in gay and bisexual men (GBM) is critical to reducing the time between HIV infection and diagnosis. Using anonymous national behavioural surveillance data (2013-2018) from 43,753 surveys of Australian GBM, we examined HIV testing frequency trends and factors differentiating PrEP-users, non-PrEP-users reporting two or more tests in the previous year, and non-PrEP-users reporting less frequent testing. The proportion tested at least annually increased from 64.4% in 2013 to 70.8% in 2018 (p-trend < 0.001), and from 73.9% to 84.6% among the 51.6% of men classified as higher-risk. Among higher-risk men, having two or more tests in the previous year increased from 48.0% to 69.3% (p-trend < 0.001). Among higher-risk non-PrEP-users, it increased from 47.2% to 54.8% (p-trend < 0.001), however, there was a decrease since 2016 (p-trend < 0.001). Among PrEP-users, it increased from 82.1% in 2013 to 97.3% in 2018 (p-trend < 0.001). Non-PrEP-using higher-risk men having less frequent tests reported lower risk than PrEP-users and non-PrEP-using men reporting two or more tests in the previous year. However, recent risk behaviour was not uncommon: nearly half reported condomless sex; one-fifth reported receptive condomless sex with ejaculation; over half reported group sex; one-quarter used drugs for the purposes of sex; and one-fifth had more than ten sex partners. Efforts are needed to encourage frequent testing and PrEP use among non-PrEP-users who are at higher-risk.

Association of obesity with hypertension and type 2 diabetes mellitus in India: A meta-analysis of observational studies.

AIM: To perform a meta-analysis of the association of obesity with hypertension and type 2 diabetes mellitus (T2DM) in India among adults. METHODS: To conduct meta-analysis, we performed comprehensive, electronic literature search in the PubMed, CINAHL Plus, and Google Scholar. We restricted the analysis to studies with documentation of some measure of obesity namely; body mass index, waist-hip ratio, waist circumference and diagnosis of hypertension or diagnosis of T2DM. By obtaining summary estimates of all included studies, the meta-analysis was performed using both RevMan version 5 and "metan" command STATA version 11. Heterogeneity was measured by I2 statistic. Funnel plot analysis has been done to assess the study publication bias. RESULTS: Of the 956 studies screened, 18 met the eligibility criteria. The pooled odds ratio between obesity and hypertension was 3.82 (95%CI: 3.39 to 4.25). The heterogeneity around this estimate (I2 statistic) was 0%, indicating low variability. The pooled odds ratio from the included studies showed a statistically significant association between obesity and T2DM (OR = 1.14, 95%CI: 1.04 to 1.24) with a high degree of variability. CONCLUSION: Despite methodological differences, obesity showed significant, potentially plausible association with hypertension and T2DM in studies conducted in India. Being a modifiable risk factor, our study informs setting policy priority and intervention efforts to prevent debilitating complications.

Glycogen Synthase Kinase 3: A Kinase for All Pathways?

Glycogen synthase kinase-3 (GSK-3) is an unusual protein-serine kinase in that it is primarily regulated by inhibition and lies downstream of multiple cell signaling pathways. This raises a variety of questions in terms of its physiological role(s), how signaling specificity is maintained and why so many eggs have been placed into one basket. There are actually two baskets, as there are two isoforms, GSK-3α and ß, that are highly related and largely redundant. Their many substrates range from regulators of cellular metabolism to molecules that control growth and differentiation. In this chapter, we review the characteristics of GSK-3, update progress in understanding the kinase, and try to answer some of the questions raised by its unusual properties. Indeed, the kinase may trigger transformation in our thinking of how cellular signals are organized and controlled.

DJ-1 links muscle ROS production with metabolic reprogramming and systemic energy homeostasis in mice.

Reactive oxygen species (ROS) have been linked to a wide variety of pathologies, including obesity and diabetes, but ROS also act as endogenous signalling molecules, regulating numerous biological processes. DJ-1 is one of the most evolutionarily conserved proteins across species, and mutations in DJ-1 have been linked to some cases of Parkinson's disease. Here we show that DJ-1 maintains cellular metabolic homeostasis via modulating ROS levels in murine skeletal muscles, revealing a role of DJ-1 in maintaining efficient fuel utilization. We demonstrate that, in the absence of DJ-1, ROS uncouple mitochondrial respiration and activate AMP-activated protein kinase, which triggers Warburg-like metabolic reprogramming in muscle cells. Accordingly, DJ-1 knockout mice exhibit higher energy expenditure and are protected from obesity, insulin resistance and diabetes in the setting of fuel surplus. Our data suggest that promoting mitochondrial uncoupling may be a potential strategy for the treatment of obesity-associated metabolic disorders.

Dysregulation of lipolysis and lipid metabolism in visceral and subcutaneous adipocytes by high-fat diet: role of ATGL, HSL, and AMPK.

This study investigated the molecular mechanisms by which a high-fat diet (HFD) dysregulates lipolysis and lipid metabolism in mouse epididymal (visceral, VC) and inguinal (subcutaneous, SC) adipocytes. Eight-weeks of HFD feeding increased adipose triglyceride lipase (ATGL) content and comparative gene identification-58 (CGI-58) expression, whereas hormone-sensitive lipase (HSL) phosphorylation and perilipin content were severely reduced. Adipocytes from HFD mice elicited increased basal but blunted epinephrine-stimulated lipolysis and increased diacylglycerol content in both fat depots. Consistent with impaired adrenergic receptor signaling, HFD also increased adipose-specific phospholipase A(2) expression in both fat depots. Inhibition of E-prostanoid 3 receptor increased basal lipolysis in control adipocytes but failed to acutely alter the effects of HFD on lipolysis in both fat depots. In HFD visceral adipocytes, activation of adenylyl cyclases by forskolin increased HSL phosphorylation and surpassed the lipolytic response of control cells. However, in HFD subcutaneous adipocytes, forskolin induced lipolysis without detectable HSL phosphorylation, suggesting activation of an alternative lipase in response to HFD-induced suppression of HSL in VC and SC adipocytes. HFD also powerfully inhibited basal, epinephrine-, and forskolin-induced AMP kinase (AMPK) activation as well peroxisome proliferator-activated receptor gamma coactivator-1alpha expression, citrate synthase activity, and palmitate oxidation in both fat depots. In summary, novel evidence is provided that defective adrenergic receptor signaling combined with upregulation of ATGL and suppression of HSL and AMPK signaling mediate HFD-induced alterations in lipolysis and lipid utilization in VC and SC adipocytes, which may play an important role in defective lipid mobilization and metabolism seen in diet-induced obesity.