Blood in the joint: effects of hemarthrosis on meniscus health and repair techniques.

Injury to the meniscus is common and frequently leads to the development of post-traumatic osteoarthritis (PTOA). Many times meniscus injuries occur coincident with anterior cruciate ligament (ACL) injuries and lead to a bloody joint effusion. Hemarthrosis, or bleeding into the joint, has been implicated in degeneration of joint tissues. The goal of this review paper is to understand the pathophysiology of blood-induced joint damage, the possible effects of blood on meniscus tissue, and the implications for current meniscus repair techniques that involve the introduction of blood-derived products into the joint. In this review, we illustrate the similarities in the pathophysiology of joint damage due to hemophilic arthropathy (HA) and osteoarthritis (OA). Although numerous studies have revealed the harmful effects of blood on cartilage and synovium, there is currently a gap in knowledge regarding the effects of hemarthrosis on meniscus tissue homeostasis, healing, and the development of PTOA following meniscus injury. Given that many meniscus repair techniques utilize blood-derived and marrow-derived products, it is essential to understand the effects of these factors on meniscus tissue and the whole joint organ to develop improved strategies to promote meniscus tissue repair and prevent PTOA development.

Osteoarthritis year in review 2018: mechanics.

OBJECTIVE: To review recent biomechanics literature focused on the interactions between biomechanics and articular cartilage health, particularly focused on macro-scale and human studies. DESIGN: A literature search was conducted in PubMed using the search terms (biomechanics AND osteoarthritis) OR (biomechanics AND cartilage) OR (mechanics AND osteoarthritis) OR (mechanics AND cartilage) for publications from April 2017 to April 2018. RESULTS: Abstracts from the 559 articles generated from the literature search were reviewed. Due to the wide range of topics, 62 full texts with a focus on in vivo biomechanical studies were included for further discussion. Several overarching themes in the recent literature were identified and are summarized, including 1) new methods to detect early osteoarthritis (OA) development, 2) studies describing healthy and OA cartilage and biomechanics, 3) ACL injury and OA development, 4) meniscus injury and OA development, and 5) OA prevention, treatment, and management. CONCLUSIONS: Mechanical loading is a critical factor in the maintenance of joint health. Abnormal mechanical loading can lead to the onset and progression of OA. Thus, recent studies have utilized various biomechanical models to better describe the etiology of OA development and the subsequent effects of OA on the mechanics of joint tissues and whole body biomechanics.

Private sex workers' engagement with sexual health services: an online survey.

This study examined where private sex workers (PSW) present for sexual health services, disclosure, services received, and their satisfaction with care. An online anonymous survey was conducted via SurveyMonkey (surveymonkey.com). Among the 53 participants, 42% attended a sexual health clinic, 24% attended a general practitioner (GP) and 34% attended both. Participants attending GPs were less likely to be offered a throat swab and opportunities for cervical screening, contraception and vaccination were often missed in both service models. Participants attending GPs were less likely to disclose sex work and were less satisfied. Better awareness of the sexual health needs of PSWs is important in GP services.

Multi-centre field evaluation of the performance of the Trinity Biotech Uni-Gold HIV 1/2 rapid test as a first-line screening assay for gay and bisexual men compared with 4th generation laboratory immunoassays.

BACKGROUND: The Trinity Biotech Uni-Gold HIV test (Uni-Gold) is often used as a supplementary rapid test in testing algorithms. OBJECTIVE: To evaluate the operational performance of the Uni-Gold as a first-line screening test among gay and bisexual men (GBM) in a setting where 4th generation HIV laboratory assays are routinely used. STUDY DESIGN: We compared the performance of Uni-Gold with conventional HIV serology conducted in parallel among GBM attending 22 testing sites. Sensitivity was calculated separately for acute and established infection, defined using 4th generation screening Ag/Ab immunoassay (EIA) and Western blot results. Previous HIV testing history and results of supplementary 3rd generation HIV Ab EIA, and p24 antigen EIA were used to further characterise cases of acute infection. RESULTS: Of 10,793 specimens tested with Uni-Gold and conventional serology, 94 (0.90%, 95%CI:0.70-1.07) were confirmed as HIV-positive by conventional serology, and 37 (39.4%) were classified as acute infection. Uni-Gold sensitivity was 81.9% overall (77/94, 95%CI:72.6-89.1); 56.8% for acute infection (21/37, 95%CI:39.5-72.9) and 98.2% for established infection (56/57, 95%CI:90.6-100.0). Of 17 false non-reactive Uni-Gold results, 16 were acute infections, and of these seven were p24 antigen reactive but antibody negative. Uni-Gold specificity was 99.9% (10,692/10,699, 95%CI:99.9-100.0), PPV was 91.7% (95%CI:83.6-96.6) and NPV was 99.8% (95%CI:99.7-99.9), respectively. CONCLUSIONS: In this population, Uni-Gold had good specificity and sensitivity was high for established infections when compared to 4th generation laboratory assays, however sensitivity was lower in acute infections. Where rapid tests are used in populations with a high proportion of acute infections, additional testing strategies are needed to detect acute infections.

Protocol for an open-label, single-arm trial of HIV pre-exposure prophylaxis (PrEP) among people at high risk of HIV infection: the NSW Demonstration Project PRELUDE.

INTRODUCTION: Despite a number of HIV prevention strategies, the number of new HIV infections remains high. In Australia, over three-quarters of new HIV diagnoses are in gay and bisexual men (GBM). Pre-exposure prophylaxis (PrEP) has been shown to be effective at preventing new HIV infections in several randomised trials. The PRELUDE study aims to evaluate the implementation of PrEP in healthcare settings in New South Wales (NSW), Australia, among a sample of high-risk adults. METHODS AND ANALYSIS: PRELUDE is an ongoing open-label, single-arm demonstration project, conducted in public and private clinics across NSW, Australia. Enrolment began in November 2014. The study is designed for 300 high-risk participants-mainly GBM and heterosexual women. Participants receive daily oral PrEP, composed of emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF), for up to 2.5 years. Quarterly study visits include testing for HIV and sexually transmitted infections (STIs), assessment of ongoing eligibility and side effects, and self-reported adherence. Following each study visit, online behavioural surveys are administered to collect information on medication adherence, risk behaviours and attitudes. Blood samples will be collected in a subset of patients 1, 6 and 12 months after PrEP initiation to measure FTC/TDF concentrations. Analyses using longitudinal regression models will focus on feasibility, adherence, safety, tolerability and effects of PrEP on behaviour. This study will inform PrEP policy and guide the implementation of PrEP in Australia in people at high risk of HIV. ETHICS AND DISSEMINATION: The study will be conducted in accordance with the Declaration of Helsinki. All patients will provide written informed consent prior to participation in the study. Publications relating to each of the primary end points will be gradually released after 12 months of follow-up is complete. TRIAL REGISTRATION NUMBER: NCT02206555; Pre-results.

Advances in combining gene therapy with cell and tissue engineering-based approaches to enhance healing of the meniscus.

Meniscal lesions are common problems in orthopaedic surgery and sports medicine, and injury or loss of the meniscus accelerates the onset of knee osteoarthritis (OA). Despite a variety of therapeutic options in the clinics, there is a critical need for improved treatments to enhance meniscal repair. In this regard, combining gene-, cell-, and tissue engineering-based approaches is an attractive strategy to generate novel, effective therapies to treat meniscal lesions. In the present work, we provide an overview of the tools currently available to improve meniscal repair and discuss the progress and remaining challenges for potential future translation in patients.

Reactive arthritis following a Microsporidia infection.

Reactive arthritis may be caused by both sexually transmissible and enteric organisms, though Microsporidia is not currently recognised as a causative agent. This case report describes the development of reactive arthritis following Microsporidia infection in an immunocompetent man.

The acceptability and cost of a home-based chlamydia retesting strategy: findings from the REACT randomised controlled trial.

BACKGROUND: Chlamydia retesting three months after treatment is recommended to detect reinfections, but retesting rates are typically low. The REACT (retest after Chlamydia trachomatis) randomised trial demonstrated that home-based retesting using postal home-collection kits and SMS reminders, resulted in substantial improvements in retesting rates in women, heterosexual men and men who have sex with men (MSM), with detection of more repeat positive tests compared with SMS reminder alone. In the context of this trial, the acceptability of the home-based strategy was evaluated and the costs of the two strategies were compared. METHODS: REACT participants (200 women, 200 heterosexual men, 200 MSM) were asked to complete an online survey that included home-testing acceptability and preferred methods of retesting. The demographics, sexual behaviour and acceptability of home collection were compared between those preferring home-testing versus clinic-based retesting or no preference, using a chi-square test. The costs to the health system of the clinic-based and home retesting strategies and the cost per infection for each were also compared. RESULTS: Overall 445/600 (74 %) participants completed the survey; 236/445 from the home-testing arm, and 141 of these (60 %) retested at home. The majority of home arm retesters were comfortable having the kit posted to their home (86 %); found it easy to follow the instructions and collect the specimens (96 %); were confident they had collected the specimens correctly (90 %); and reported no problems (70 %). Most (65 %) preferred home retesting, 21 % had no preference and 14 % preferred clinic retesting. Comparing those with a preference for home testing to those who didn't, there were significant differences in being comfortable having a kit sent to their home (p = 0.045); not having been diagnosed with chlamydia previously (p = 0.030); and living with friends (p = 0.034). The overall cost for the home retest pathway was $154 (AUD), compared to $169 for the clinic-based retesting pathway and the cost per repeat infection detected was $1409 vs $3133. CONCLUSIONS: Among individuals initially diagnosed with chlamydia in a sexual health clinic setting, home-based retesting was shown to be highly acceptable, preferred by most participants, and cost-efficient. However some clients preferred clinic-based testing, often due to confidentiality concerns in their home environment. Both options should be provided to maximise retesting rates. TRIAL REGISTRATION: The trial was registered with the Australia New Zealand Clinical Trials Registry on September 9, 2011: ACTRN12611000968976.

Reactive arthritis at the Sydney Sexual Health Centre 1992-2012: declining despite increasing chlamydia diagnoses.

Reactive arthritis is an under-studied complication of genital Chlamydia trachomatis infection (chlamydia). We assessed trends and risk factors for reactive arthritis in a large urban sexual health clinic. Using a case-control design, data on reactive arthritis cases and controls at the Sydney Sexual Health Centre over the period 1992-2012 were extracted and multivariate analyses were performed. Trend analyses were performed on reactive arthritis diagnoses. Over the 1992-2012 study period, 85 reactive arthritis cases were diagnosed at Sydney Sexual Health Centre. The rate of reactive arthritis diagnoses decreased over time (23 in 1992-1996 to one in 2007-2011 and none in 2012), while chlamydia diagnoses increased (770 in 1992-1996 to 2257 in 2007-2011). In multivariate analysis, factors independently associated with a reactive arthritis diagnosis were: being male (adjusted odds ratio [aOR] 3.27; 95% confidence interval [CI] 1.04-10.32; p = 0.043) or born overseas (aOR 2.69; 95% CI 1.27-5.70; p = 0.010), while a past sexually transmitted infection other than chlamydia or non-gonococcal urethritis was protective (aOR 0.21; 95% CI 0.10-0.45; p < 0.001). Reactive arthritis was not associated with current or recent chlamydia infection (p = 0.184) but was marginally associated with past non-gonococcal urethritis (p = 0.080). This study found a decline in reactive arthritis diagnoses despite an increase in chlamydia diagnoses.

Effect of testing experience and profession on provider acceptability of rapid HIV testing after implementation in public sexual health clinics in Sydney.

OBJECTIVES: Rapid HIV testing (RHT) is well established in many countries, but it is new in Australia since a policy change in 2011. We assessed service provider acceptability of RHT before and after its implementation in four Sydney public sexual health clinics. METHODS: Service providers were surveyed immediately after training in RHT and again 6-12 months later. Differences in mean scores between survey rounds were assessed via t-tests, with stratification by profession and the number of tests performed. RESULTS: RHT was rated as highly acceptable among staff at baseline and acceptability scores improved between survey rounds. Belief in being sufficiently skilled and experienced to perform RHT (P = 0.004) and confidence in the delivery of nonreactive results increased (P = 0.007), while the belief that RHT was disruptive declined (P = 0.001). Acceptability was higher for staff who had performed a greater number of tests regarding comfort with their role in RHT (P = 0.004) and belief that patients were satisfied with RHT (P = 0.007). Compared with nurses, doctors had a stronger preference for a faster rapid test (P = 0.027) and were more likely to agree that RHT interfered with consultations (P = 0.014). CONCLUSIONS: Differences in responses between professions may reflect differences in staff roles, the type of patients seen by staff and the model of testing used, all of which may affect the number of tests performed by staff. These findings may inform planning for how best to implement RHT in clinical services.

Raltegravir-emtricitabine-tenofovir as HIV nonoccupational post-exposure prophylaxis in men who have sex with men: safety, tolerability and adherence.

OBJECTIVES: Three-drug nonoccupational post-exposure prophylaxis (NPEP) typically includes co-formulated emtricitabine-tenofovir (FTC-TDF) and a protease inhibitor. However, protease inhibitors can cause significant toxicities, can interact with prescribed and illicit drugs, and work late in the viral cycle. Agents that act before viral integration into host DNA may have efficacy advantages. Raltegravir (RAL) is a good candidate for NPEP as it has few side effects or drug interactions and acts prior to HIV integration. The objective of this study was to investigate the use of RAL in 3-drug NPEP in terms of safety, adherence and tolerability. METHODS: We evaluated 28 days of RAL-FTC-TDF treatment in 86 men and FTC-TDF treatment in 34 men eligible for three- and two-drug NPEP, respectively. We assessed adherence (compared between groups and with nonstudy controls) and clinical and adverse events at weeks 1, 2 and 4, and efficacy at week 12. Analyses were by intention to treat, excluding from the adherence analysis subjects who ceased NPEP because their source was HIV-uninfected. RESULTS: No participant became infected with HIV. For RAL-FTC-TDF and FTC-TDF, regimen completion rates were 92% and 91% and medication adherence rates were 89% and 90%, respectively. Eight (9%) RAL recipients developed mild myalgias, with four developing transient grade 4 elevations in creatine kinase (two developed both), all of which improved to grade 2 or less by week 4 without RAL discontinuation. Eight prescribed and 37 potential illicit drug interactions with a protease inhibitor were avoided by use of RAL. CONCLUSIONS: RAL-FTC-TDF is well tolerated as NPEP, results in high levels of adherence and avoids potential drug-drug interactions. Patients and clinicians should be aware of the potential for acute muscle toxicity when RAL is used as NPEP.

Is azithromycin adequate treatment for asymptomatic rectal chlamydia?

Rectal chlamydia is a common sexually transmissible infection (STI) in men who have sex with men (MSM) that is predominantly asymptomatic. The recommended treatment of azithromycin 1 g as a single oral dose has not been subject to randomized trials and so its efficacy is unknown. We conducted a retrospective case-note review of all MSM diagnosed at the Sydney Sexual Health Centre with asymptomatic rectal chlamydia in 2009. We identified 116 MSM who received azithromycin; 85 (73%) attended for the recommended re-test at varying times (median 78 days, range 21-372 days). Of the men who returned, 11 (13%) had a persistently positive result; we reviewed behavioural data to classify these men as probable re-infections (6/11) or possible treatment failures (5/11), suggesting an efficacy of 94%. Until a randomized controlled trial (RCT) is conducted, patients with rectal chlamydia should be encouraged to attend for a re-test at 6-12 weeks.

Short message service reminder intervention doubles sexually transmitted infection/HIV re-testing rates among men who have sex with men.

OBJECTIVES: To evaluate the impact of a short message service (SMS) reminder system on HIV/sexually transmitted infection (STI) re-testing rates among men who have sex with men (MSM). METHODS: The SMS reminder programme started in late 2008 at a large Australian sexual health clinic. SMS reminders were recommended 3-6 monthly for MSM considered high-risk based on self-reported sexual behaviour. The evaluation compared HIV negative MSM who had a HIV/STI test between 1 January and 31 August 2010 and received a SMS reminder (SMS group) with those tested in the same time period (comparison group) and pre-SMS period (pre-SMS group, 1 January 2008 and 31 August 2008) who did not receive the SMS. HIV/STI re-testing rates were measured within 9 months for each group. Baseline characteristics were compared between study groups and multivariate logistic regression used to assess the association between SMS and re-testing and control for any imbalances in the study groups. RESULTS: There were 714 HIV negative MSM in the SMS group, 1084 in the comparison group and 1753 in the pre-SMS group. In the SMS group, 64% were re-tested within 9 months compared to 30% in the comparison group (p<0.001) and 31% in the pre-SMS group (p<0.001). After adjusting for baseline differences, re-testing was 4.4 times more likely (95% CI 3.5 to 5.5) in the SMS group than the comparison group and 3.1 times more likely (95% CI 2.5 to 3.8) than the pre-SMS group. CONCLUSION: SMS reminders increased HIV/STI re-testing among HIV negative MSM. SMS offers a cheap, efficient system to increase HIV/STI re-testing in a busy clinical setting.

Dynamic loading enhances integrative meniscal repair in the presence of interleukin-1.

OBJECTIVE: Meniscal tears are a common knee injury and increased levels of interleukin-1 (IL-1) have been measured in injured and degenerated joints. Studies have shown that IL-1 decreases the shear strength, cell accumulation, and tissue formation in meniscal repair interfaces. While mechanical stress and IL-1 modulate meniscal biosynthesis and degradation, the effects of dynamic loading on meniscal repair are unknown. The purpose of this study was to determine the effects of mechanical compression on meniscal repair under normal and inflammatory conditions. EXPERIMENTAL DESIGN: Explants were harvested from porcine medial menisci. To simulate a full-thickness defect, a central core was removed and reinserted. Explants were loaded for 4h/day at 1 Hz and 0%-26% strain for 14 days in the presence of 0 or 100 pg/mL of IL-1. Media were assessed for matrix metalloproteinase (MMP) activity, aggrecanase activity, sulfated glycosaminoglycan (S-GAG) release, and nitric oxide (NO) production. After 14 days, biomechanical testing and histological analyses were performed. RESULTS: IL-1 increased MMP activity, S-GAG release, and NO production, while decreasing the shear strength and tissue repair in the interface. Dynamic loading antagonized IL-1-mediated inhibition of repair at all strain amplitudes. Neither IL-1 treatment nor strain altered aggrecanase activity. Additionally, strain alone did not alter meniscal healing, except at the highest strain magnitude (26%), a level that enhanced the strength of repair. CONCLUSIONS: Dynamic loading blocked the catabolic effects of IL-1 on meniscal repair, suggesting that joint loading through physical therapy may be beneficial in promoting healing of meniscal lesions under inflammatory conditions.

The behaviour and sexual health of young international travellers (backpackers) in Australia.

OBJECTIVES: To study the demographics, risk behaviours and morbidity of young long-term international travellers (backpackers) attending a sexual health service in Sydney, Australia. METHODS: Data on new patients were extracted from the Sydney Sexual Health Centre database for the period 1998 to 2006. The sexual risk behaviours and morbidity of the backpackers were compared with other patients of a similar age. RESULTS: The 5698 backpackers who attended the centre reported higher numbers of sexual partners (three or more partners in the past 3 months, 18% vs 12%, p<0.001) and a greater proportion drank alcohol at hazardous levels (22%) than the comparison group (9%, p<0.001). Rates of consistent (100%) condom use in the past 3 months were low in both backpackers (22%) and the comparison population (19%). Backpackers had higher rates of genital chlamydia infection (7% vs 5%, p<0.001) and reported higher rates of previous sexually transmitted infections (15% vs 10%, p<0.001). CONCLUSIONS: Backpackers should be a priority population for sexual health promotion and access to services.

Increasing role of herpes simplex virus type 1 in first-episode anogenital herpes in heterosexual women and younger men who have sex with men, 1992-2006.

OBJECTIVES: Herpes simplex virus (HSV) type 1 is causing an increasing proportion of anogenital herpes; however, it is unclear which populations are affected. We describe the contribution of HSV-1 to first-episode anogenital herpes and its associations. METHODS: For all cases of first-episode anogenital herpes diagnosed at the Sydney Sexual Health Centre from 1992 to 2006, medical record review was used to confirm the type and anatomical site. Age, sex, HIV status and sexual behaviour data were extracted from the clinic database. RESULTS: Overall, among 1845 confirmed cases of first-episode anogenital herpes the proportion attributable to HSV-1 increased from 29% to 42% (odds ratio (OR) per 3-year band 1.19; 95% CI 1.11 to 1.27). When stratified by gender of sexual partners the proportion of first-episode anogenital herpes due to HSV-1 increased over time, but only achieved significance in heterosexual women (p<0.01). Among men who have sex with men (MSM), HSV-1 only increased for those less than 28 years of age, 17% in 1992-4 to 76% in 2004-6 (OR per 3-year band 1.58; 95% CI 1.14 to 2.19). The proportion attributable to HSV-1 was higher for anal than genital herpes and MSM were much more likely to have anal disease. CONCLUSIONS: The proportion of first-episode anogenital herpes due to HSV-1 significantly increased among younger MSM and heterosexual women over the 15-year period. In some clinical populations, such as young MSM and women or patients with anal disease, HSV-1 may now account for the majority of first-episode anogenital herpes.

Gonorrhoea screening in general practice: perceived barriers and strategies to improve screening rates.

OBJECTIVE: To investigate perceived barriers to gonorrhoea screening in general practice and suggest strategies to overcome them. DESIGN: Questionnaire-based survey. SETTING AND PARTICIPANTS: All 47 general practitioners (GPs) authorised to prescribe subsidised HIV drugs under the Pharmaceutical Benefits Scheme in inner, eastern and northern Sydney. MAIN OUTCOME MEASURES: Agreement on a five-point Likert scale with statements about attitudes and practices in relation to gonorrhoea screening of homosexually active men, and views on how testing rates could be increased. RESULTS: 32 GPs responded (68%). Perceived barriers to gonorrhoea testing included structural measures imposed by the Federal Government to limit pathology testing by GPs (the Medicare "three-test rule") (17 respondents agreed or strongly agreed), pressure from the Health Insurance Commission (HIC) to minimise pathology testing (15), concerns about confidentiality of notification procedures (8), clinical time pressure (8), and concerns about recriminations against HIV patients with gonorrhoea (6). Suggested measures to increase testing were education of gay men to request testing (25), relaxation of the three-test rule (25), easier tests (23), anonymous notification procedures, review of HIC policy on screening, and training about testing (21 each). CONCLUSIONS: Sydney GPs with high HIV caseloads perceived structural barriers to gonorrhoea testing and supported a range of achievable strategies to overcome these. As the sustained epidemic of gonorrhoea in Sydney may be directly promoting HIV transmission, these strategies should be considered urgently.