Increased targeted HIV testing and reduced undiagnosed HIV infections among gay and bisexual men.

OBJECTIVES: To evaluate the impact of government HIV strategies that aimed to increase HIV testing uptake and frequency among gay and bisexual men (GBM) in New South Wales (NSW), Australia. DESIGN: We analysed HIV testing data from existing passive and sentinel surveillance systems between 2010 and 2018. METHODS: Six indicators were measured: (1) state-wide total HIV laboratory tests; (2) number of GBM attending publicly-funded clinics; (3) 12-monthly testing uptake; (4) annual testing frequency; (5) HIV testing with a STI diagnosis; and (6) HIV positivity. Mathematical modelling was used to estimate (7) the proportion of men with undiagnosed HIV. Indicators were stratified by Australian vs. overseas-born. RESULTS: Overall, 43,560 GBM attended participating clinics (22,662 Australian-born, 20,834 overseas-born) from 2010-2018. Attendees increased from 5,186 in 2010 to 16,507 in 2018. There were increasing trends (p<0.001 for all) in testing uptake (83.9% to 95.1%); testing with a STI diagnosis (68.7% to 94.0%); annual HIV testing frequency (1.4 to 2.7); and a decreasing trend (p<0.01) in HIV positivity (1.7% to 0.9%).Increases in testing were similar in Australian-born and overseas-born GBM. However, there were decreasing trends in the estimated undiagnosed HIV proportion overall (9.5% to 7.7%) and in Australian-born GBM (7.1% to 2.8%), but an increasing trend in overseas-born GBM (15.3% to 16.9%) (p<0.001 for all).

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.

A longitudinal cohort study of HIV 'treatment as prevention' in gay, bisexual and other men who have sex with men: the Treatment with Antiretrovirals and their Impact on Positive And Negative men (TAIPAN) study protocol.

BACKGROUND: Australia has increased coverage of antiretroviral treatment (ART) over the past decade, reaching 73% uptake in 2014. While ART reduces AIDS-related deaths, accumulating evidence suggests that it could also bolster prevention efforts by reducing the risk of HIV transmission ('treatment as prevention'). While promising, evidence of community-level impact of treatment as prevention on reducing HIV incidence among gay and bisexual men is limited. We describe a study protocol that aims to determine if scale up of testing and treatment for HIV leads to a reduction in community viraemia and, in turn, if this reduction is temporally associated with a reduction in HIV incidence among gay and bisexual men in Australia's two most populous states. METHODS: Over the period 2009 to 2017, we will establish two cohorts making use of clinical and laboratory data electronically extracted retrospectively and prospectively from 73 health services and laboratories in the states of New South Wales and Victoria. The 'positive cohort' will consist of approximately 13,000 gay and bisexual men (>90% of all people living with HIV). The 'negative cohort' will consist of at least 40,000 HIV-negative gay and bisexual men (approximately half of the total population). Within the negative cohort we will use standard repeat-testing methods to calculate annual HIV incidence. Community prevalence of viraemia will be defined as the proportion of men with a viral load ≥200RNA copies/mm3, which will combine viral load data from the positive cohort and viraemia estimates among those with an undiagnosed HIV infection. Using regression analyses and adjusting for behavioural and demographic factors associated with infection, we will assess the temporal association between the community prevalence of viraemia and the incidence of HIV infection. Further analyses will make use of these cohorts to assess incidence and predictors of treatment initiation, repeat HIV testing, and viral suppression. DISCUSSION: This study will provide important information on whether 'treatment as prevention' is associated with a reduction in HIV incidence at a community level among gay and bisexual men.

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.

The acceptability of different HIV testing approaches: cross-sectional study among GMSM in Australia.

BACKGROUND: We explored the attitudes of Australian gay and other men who have sex with men (GMSM) about the current standard-of-care (non-rapid tests at healthcare settings) and alternative approaches (rapid tests and testing in non-healthcare settings) to better understand the acceptability of alternative testing approaches. METHODS: The Contemporary Norms in Networks and Communities of GMSM study enrolled GMSM in Sydney, Melbourne and Perth in 2011-2012 using peer referrals. We explored the self-reported preferences for testing: rapid versus non-rapid and in non-healthcare settings (community-based or home-based testing) versus in healthcare settings, and examined factors associated with preferences for these approaches. Analyses of associations used standard univariate and age-adjusted logistic regression models. RESULTS: Among 827 sexually active non-HIV-positive participants, 89% had been tested for HIV. Most preferred by participants was home rapid testing (46%), followed by standard-of-care (23%) and rapid testing in healthcare (20%) or community settings (7%). About 73% of participants preferred rapid over non-rapid testing, and 56% preferred testing in non-healthcare settings rather than in healthcare settings. Preference for rapid testing was associated with being fully employed (adjusted OR (aOR): 1.81; 95% CI 1.16 to 2.82), managerial/professional occupation (aOR: 2.03; 95% CI 1.19 to 3.46) and engaging in unprotected anal intercourse with casual partners (aOR: 1.89; 95% CI 1.29 to 2.78). The same factors were associated with preference for testing in non-healthcare settings. CONCLUSIONS: Australian GMSM prefer alternative testing approaches, possibly due to their convenience. The availability of new testing approaches may provide more options for GMSM at risk for HIV infection, improve access to HIV testing and potentially increase HIV testing rates.

Use of the Iowa Self-Assessment Inventory with older hospitalized patients.

This study examined the utility of the Iowa Self-Assessment Inventory (ISAI) as a multidimensional screening tool for older adults in the acute care hospital setting. A sample of 98 patients age 60 and older were administered the ISAI, the Short Geriatric Depression Scale, and the Mini-Mental State Examination. The findings suggest the ISAI is useful for screening for depression but does not detect differences in cognition. However, qualitative data and literature review support the continued search for a holistic, humanistic screening tool to increase the quality and effectiveness of patient care.

Use of protease inhibitors increases the amounts of substance P extracted from small specimens of nerve tissue.

When using radioimmunoassay to measure the levels of peptides from small pieces of nerve tissue it is crucial to maximize the amount of peptides extracted. Here we report on the value of including protease inhibitors in the extraction buffer when extracting substance P (SP) from short lengths of rat saphenous nerve tissue. Nerve segments were removed from terminally anesthetized 13-week-old rats and directly added to acid buffer (including EDTA) either with or without 1 mM 4-(2-amino-ethyl)-benzesulfonyl fluoride-HCl, 2 micrograms/ml aprotinin, 100 microM leupeptin, 1 microgram/ml cystatin, and 1 mM benzamidine. These "direct" samples were then boiled for 10 min. With additional groups of pieces of saphenous nerve tissue the effects of leaving the samples for 10 min in both buffers at room temperature either intact ("delayed") or after mincing the tissue ("minced") were investigated. Addition of protease inhibitors increased the amount of SP extracted in both direct and delayed procedures, although the increase was only significant for the delayed situation (P < or = 0.05). "Delay" in the absence of protease inhibitors resulted in a significantly decreased amount of SP being extracted compared to the direct and minced situations (P < or = 0.05). We recommend use of protease inhibitors be included as part of the standard procedure for extracting neuropeptides from small specimens of nerve tissue for radioimmunoassay.

Leucocyte and erythrocyte counts during a multi-stage cycling race ('the Milk Race').

Venous blood samples were taken from eight competitors in mid-evening after a racing day, and in the early morning before the next day's race, three times during the course of the Milk Race, 1992. These were used to gather information about the changes in circulating leucocyte levels in response to the exceptionally high sustained daily workload required during a major multi-stage race. The primary objective was to provide knowledge of 'normal' values against which future clinical judgements of abnormality might be made in these unusual circumstances. During the race, estimated energy output was about 25 MJ (6000 kCal)/day. The mean total circulating leucocyte numbers (per litre of blood), and those of individual leucocyte classes (neutrophil, lymphocyte, monocyte, eosinophil and basophil) were all inside the normal range both in the morning and in the evening. Evening counts were, however, 30-50% higher than morning counts, for all classes except eosinophils. We conclude that individual clinical decisions about leucocyte levels can best be made using normal (sedentary man) values if a morning sample is taken.

Effect of exercise on simple reaction times of recreational athletes.

To examine the effect of moderate and fatiguing exercise on the simple reaction times of recreational athletes, 12 subjects took a simple reaction-time test while at rest and while cycling on a Monark cycle ergometer at 70% and 100% of maximum workload. To estimate 70% and 100% of maximum workload the subjects underwent a standard incremental test until exhaustion, defined as subjects being unable to maintain the required pedal rate of 70 rpm. Simple reaction time during maximal exercise was significantly slower than in the other two conditions which did not differ significantly from one another. Heart rate and rate of perceived exertion differed significantly for all three conditions.

Multiple personality disorder and borderline personality disorder. Distinct entities or variations on a common theme?

We report data from a comparison of 14 subjects with multiple personality disorder (MPD) and 13 subjects with borderline personality disorder (BPD). There were few significant differences between the groups. The authors discuss the concept of MPD as an epiphenomenon of BPD, and argue their fundamental similarity.

Morphine, but not sodium cromoglycate, modulates the release of substance P from capsaicin-sensitive neurones in the rat trachea in vitro.

1. Opioids have been shown to inhibit substance P (SP) release from primary afferent neurones (PAN). In addition, opioid receptors have been identified on PAN of the vagus nerves. Sodium cromoglycate (SCG) decreases the excitability of C-fibres in the lung of the dog in vivo. We have utilised a multi-superfusion system to investigate the effect of opioids and SCG on the release of SP from the rat trachea in vitro. 2. Pretreatment of newborn rats with capsaicin (50 mg kg-1 s.c. at day 1 and 2 of life) resulted in a 93.2 +/- 6.3% reduction in tracheal substance P-like immunoreactivity (SP-LI) content when determined by radioimmunoassay in the adult. 3. Exposure to isotonically elevated potassium concentrations (37-90 mM), capsaicin (100 nM-10 microM), and bradykinin (BK; 10nm-1 microM) but not des-Arg9-BK (1 microM) stimulated SP-LI release by a calcium-dependent mechanism. 4. SCG (1 microM and 100 microM) did not affect spontaneous, potassium (60 mM)- or BK (1 microM)-stimulated SP-LI release. 5. Morphine (0.1-100 microM) caused dose-related inhibition of potassium (60 mM)-stimulated SP-LI release with the greatest inhibition of 60.4 +/- 13.7% at 100 microM. The effect of morphine was not mimicked by the kappa-opioid receptor agonist, U50,488H (10 microM) or the delta-opioid receptor agonist, Tyr-(D-Pen)-Gly-Phe-(D-Pen) (DPDPE). 6. The effect of morphine was totally abolished by prior and concomitant exposure to naloxone (100 nM) which had no effect on control release values. 7. We conclude that opioid receptors, predominantly of the MM-opioid receptor subtype, inhibit SP-LI release from PAN in the rat trachea and suggest that centrally inactive MM-opioid receptor agonists may have therapeutic potential in the treatment of asthma.

GABAB receptor modulation of the release of substance P from capsaicin-sensitive neurones in the rat trachea in vitro.

1. The role of gamma-aminobutyric acid (GABA) as an inhibitory transmitter in the central nervous system is well documented. Recently, GABAA and GABAB receptors have been identified in the peripheral nervous system, notably on primary afferent neurones (PAN). We have utilised a multi-superfusion system to investigate the effect of selective GABA receptor agonists and antagonists on the release of substance P (SP) from the rat trachea in vitro. 2. GABA (1-100 microM) did not affect spontaneous release of SP-like immunoreactivity (LI) but caused dose-related inhibition of calcium-dependent potassium (60 mM)-stimulated SP-LI release. The greatest inhibition of 77.7 +/- 18.8% was observed at 100 microM. 3. The inhibitory effect of GABA was mimicked by the GABAB receptor agonist, (+/-)-baclofen (1-100 microM), but not the GABAA receptor agonist, 3-amino-1-propane-sulphonic acid (3-APS, 1-100 microM). Baclofen (100 microM) had no effect on SP-LI release stimulated by capsaicin (1 microM). 4. The inhibitory effect of baclofen (30 microM) was significantly reduced by prior and concomitant exposure to the GABAB receptor antagonist, phacolofen (100 microM) but not the GABAA receptor antagonist, bicuculline (10 microM). Neither antagonist, alone, affected spontaneous or potassium-stimulated SP-LI release. 5. We conclude that activation of pre-synaptic GABAB receptors on the peripheral termini of PANs in the rat trachea inhibits SP-LI release and suggest that GABAB receptor agonists may be of value in the therapeutic treatment of asthma.

Axonal transport of substance P-like immunoreactivity in ganglioside-treated diabetic rats.

This study examined the effect of treatment of control and streptozotocin-diabetic rats with a mixture of gangliosides, derived from bovine brain, on parameters of axonal transport of substance P-like immunoreactivity (SPLI) and its levels in sciatic nerve and lumbar spinal ganglia. Rats were treated daily (10 mg/kg i.p.) for 28 days and compared with untreated control and diabetic groups. The duration of diabetes was 28 days in both cases. Untreated diabetic rats showed deficits in accumulation of axonally transported SPLI proximal (59% of controls) and distal (34% of controls) to sciatic nerve ligations (left in place for 12 h). Rates of accumulation were unaltered by diabetes. There were small numerical reductions in the SPLI content of unconstricted sciatic nerve and of L4 and L5 dorsal root ganglia in diabetic rats. None of these diabetes-associated changes was altered by ganglioside treatment, nor was there any indication of an effect of gangliosides on substance P in non-diabetic rats. The implications are discussed in relation to the possible pathogenesis of diabetic neuropathy.

Penetration of antibiotics into bovine neutrophils and their activity against intracellular Staphylococcus aureus.

The penetration of three antibiotics, penicillin, chloramphenicol and erythromycin into bovine neutrophils, either alone or containing previously ingested Staphylococcus aureus, was determined, and their intracellular activity against these bacteria was measured. Uptake of radiolabelled antibiotics was assessed by rapidly separating neutrophils from extracellular antibiotic by centrifugation through silicone oil. Intracellular activity was estimated by comparing the numbers of bacteria surviving intracellularly in neutrophils exposed to antibiotic for 3 h at ten times the MBC, with those surviving intracellularly in untreated neutrophils. Penicillin was slightly concentrated within the neutrophils, reaching a maximum intracellular concentration 1.75 times that of the extracellular concentration; this is the C/E ratio. Chloramphenicol entered to a greater extent with a maximum C/E ratio of 7.08. Erythromycin became highly concentrated within the neutrophils with a C/E ratio of 11.46 after 90 min incubation. The presence of ingested staphylococci significantly reduced the uptake of chloramphenicol, but had no significant effect on the penetration of the other antibiotics. Intracellular activity studies indicated that, at ten times MBC, only penicillin had any significant activity against intracellular staphylococci, reducing survival by 28%. This work demonstrates that penetration of certain antibiotics can be altered by the presence of ingested staphylococci and that high intracellular levels of antibiotics do not necessarily ensure good intracellular activity against pathogenic micro-organisms.

Essential fatty acid treatment--effects on nerve conduction, polyol pathway and axonal transport in streptozotocin diabetic rats.

This study was designed to examine the effect of dietary supplementation with essential fatty acids (evening primrose oil--5% weight:weight added to the diet) on acute neurophysiological and neurochemical defects in streptozotocin-diabetic rats. Diabetic rats, which were not given evening primrose oil, showed highly significant elevations of nerve sorbitol and fructose combined with a depletion of nerve myo-inositol. In those animals there was also a 40% reduction (p less than 0.02) in the accumulation of axonally transported substance P-like immunoreactivity proximal to a 12 h sciatic nerve ligature together with reduced motor nerve conduction velocity (13% [p less than 0.001] and 20% [p less than 0.001] in two separate experiments). Treatment of other diabetic rats with evening primrose oil prevented completely the development of the motor nerve conduction velocity deficit without affecting sorbitol, fructose or myo-inositol levels or the deficit in axonal transport of substance P. In a second experiment, treatment of diabetic rats with evening primrose oil was associated with significant attenuation of the conduction velocity deficit, but not complete prevention.

Oral contraceptive use in women with chronic medical conditions.

Health care practitioners are often faced with the dilemma of whether or not to provide oral contraceptives to women who have certain chronic medical conditions. This article reviews literature regarding the use of oral contraceptives in clients with histories of gestational diabetes, mitral valve prolapse or sickle cell disease. Recommendations for management are provided regarding oral contraceptive use in women with these conditions.

PIP: Health care practitioners are often faced with the dilemma of whether or not to provide oral contraceptives (OCs) to women who have certain chronic medical conditions. Oral contraceptive use among gestational diabetics who use OCs may be at increased risk for developing insulin- dependent diabetes. It appears that progestins are primarily responsible because they decrease the number of insulin receptors on cell membranes. Norgestrel has a more marked effect on carbohydrate metabolism than norethindrone. Estrogen may also play a role by slowing the uptake of glucose. Findings of available studies show that progestin only OCs, combined, low-dose OCs (35 mcg of ethinyl estradiol), or preparations with norethindrone are relatively safe for gestational diabetics. In mitral valve prolapse (MVP) abnormal hemodynamics at the prolapsed valve may promote formation of thrombi and lead to cerebrovascular accidents (CVAs). Oral contraceptives are also known to increase the incidence of thrombi, especially in the lower extremities. A 1986 study of 11 OC users who had had CVAS found that a specific subject of women with MVP are at risk for CVA, perhaps due to persistent clotting abnormalities, however most could safely use a combined, low-dose pill unless headaches, smoking, and MVP symptoms. Oral contraceptive use has usually been avoided in women with sickle cell disease. The major concern has been the possibility of an additive or synergistic effect of OCs on the blood-clotting mechanism. However sickle cell disease is a relative contraindication. Several studies showed that OC use, even up to 54 months, did not increase sickle cell crises, and only 5 cases of thromboses have been reported. The increase of fetal and maternal mortality, however, is a definite risk, therefore a similar low-dose pill may be safe for women with the sickle cell trait.