Immunological and virological response to initial antiretroviral therapy among older people living with HIV in the Canadian Observational Cohort (CANOC).

OBJECTIVES: The aim of this study was to assess the adequacy of immunological recovery and virological suppression in response to antiretroviral therapy (ART) in the growing population of older people living with HIV (PLWH), as treatment regimens become more effective and tolerable. METHODS: An interprovincial Canadian cohort of treatment-naïve PLWH who initiated ART after 1 January 2000 was used and age assessed in decades. Longitudinal absolute CD4 count response to treatment was modelled using generalized estimating equations. Cumulative incidence functions and proportional hazards models with a competing risk of death were used to estimate time to: (1) CD4 ≥ 200 cells/µL, (2) CD4 ≥ 500 cells/µL, (3) virological suppression (≤ 50 copies/mL), and (4) virological failure (> 200 copies/mL). RESULTS: In all, 12 489 individuals starting ART between 2000 and 2016 with one or more post-treatment CD4 count or viral load were included in the analysis. Age > 60 years was associated with lower absolute CD4 recovery (adjusted ß = -31 cells/µL) compared with age ≤ 30 years when pre-treatment CD4 count and other covariates were accounted for. Older age groups were less likely to achieve a CD4 ≥ 500 cells/µL, with the greatest effect in the > 60 group [adjusted hazard ratio (aHR) = 0.69, 95% confidence interval (CI): 0.57-0.84 vs. age ≤ 30). Older age groups were more likely to achieve viral suppression (age > 60, aHR = 1.20, 95% CI: 1.05-1.37) and less likely to have virological failure (age > 60, aHR = 0.46, 95% CI: 0.3-0.71) compared with those aged ≤ 30 years. CONCLUSIONS: Older adults have robust virological responses to ART; however, individuals over the age 60 are more likely to experience blunted CD4 recovery.

Depression, stress and self-stigma towards seeking psychological help in veterinary students.

Previous research indicates that the prevalence of depression among veterinarians and veterinary students is high. Although self-stigma in seeking psychological help is reportedly elevated in veterinary students, its impact on mental health has been largely unexplored. The aim of this study was to compare the levels of study-related stress, depression symptoms and self-stigma in veterinary students with those of non-veterinary students, and examine whether stress and self-stigma positively predicted depression symptoms in veterinary students. A total of 287 veterinary students and 317 non-veterinary students from Australian universities completed an online questionnaire measuring study-related stress, self-stigma and depression symptoms. Results showed that veterinary students reported significantly higher levels of stress and self-stigma than non-veterinary students, but there was no significant difference between veterinary and non-veterinary students in depression symptoms. Multiple regression analysis indicated that stress and self-stigma both predicted depression symptoms in veterinary students. These findings suggest that reducing stress and help-seeking self-stigma in veterinary students may be important in improving their wellbeing levels. These findings are important in developing a whole-of-career life course approach to understanding the professional and psychological experiences of veterinarians.

Retinal microvascular parameters are not significantly associated with mild cognitive impairment in the Northern Ireland Cohort for the Longitudinal Study of Ageing.

BACKGROUND: The retinal and cerebral microvasculature share similar embryological origins and physiological characteristics. Improved imaging technologies provide opportunistic non-invasive assessment of retinal microvascular parameters (RMPs) against cognitive outcomes. We evaluated baseline measures for associations between RMPs and mild cognitive impairment (MCI) from participants of the Northern Ireland Cohort for the Longitudinal Study of Ageing (NICOLA). METHODS: RMPs (central retinal arteriolar / venular equivalents, arteriole to venular ratio, fractal dimension and tortuosity) were measured from optic disc centred fundus images and analysed using semi-automated software. Associations between RMPs and MCI were assessed by multivariable logistic regression with adjustment for potential confounders including age, sex, alcohol consumption, smoking status, educational attainment, physical activity, cardiovascular disease (CVD), hypertension, mean arterial blood pressure, triglycerides, diabetes, body mass index, and high density lipoprotein levels. P < 0.05 was considered statistically significant. RESULTS: Data were available for 1431 participants, of which 156 (10.9%) were classified with MCI defined by a Montreal Cognitive Assessment (MoCA) score ≤ 26, with subjective cognitive decline, in the absence of depression or problems with activities of daily living. Participants had a mean age of 62.4 ± 8.5 yrs. and 52% were female. As expected, individuals with MCI had a lower MoCA score than those without (23.5 ± 2.6 versus 26.3 ± 2.7, respectively), were more likely to be female, have a lower level of educational attainment, be less physically active, more likely to have CVD, have higher levels of triglycerides and lower levels of high density lipoprotein. No significant associations between RMPs and MCI were detected in unadjusted, minimally adjusted or fully adjusted regression models or subsequent sensitivity analyses. CONCLUSION: Previous studies have reported both increased retinal venular calibre and reduced fractal dimension in association with mild cognitive impairment. Our study failed to detect any associations between RMPs and those individuals at an early stage of cognitive loss in an older community-based cohort.

Association of reduced retinal arteriolar tortuosity with depression in older participants from the Northern Ireland Cohort for the Longitudinal Study of Ageing.

INTRODUCTION: The retina shares similar anatomical and physiological features with the brain and subtle variations in retinal microvascular parameters (RMPs) may reflect similar vascular variation in the brain. The aim of this study was to assess associations between RMPs and measures of depression in the Northern Ireland Cohort for the Longitudinal Study of Ageing. METHODS: RMPs (arteriolar and venular caliber, fractal dimension and tortuosity) were measured from optic disc centred fundus images using semi-automated software. Depression was characterised by the Centre for Epidemiologic Studies Depression Scale (CES-D) in the absence of mild cognitive impairment or use of anti-depressive medications. Associations between depression and RMPs were assessed by regression analyses with adjustment for potential confounders. RESULTS: Data were available for 1376 participants of which 113 (8.2%) and 1263 (91.8%) were classified with and without depression. Participants had a mean age of 62.0 ± 8.4 yrs., 52% were female, and 8% were smokers. Individuals with depression had a higher CES-D score than those without (22.0 ± 6.2 versus 4.4 ± 3.9). Lower values of arteriolar tortuosity were significantly associated with depression, before and after adjustment for potential confounders (odds ratio = 0.79; 95% confidence intervals: 0.65, 0.96; P = 0.02). CONCLUSION: Decreased retinal arteriolar tortuosity, a measure of the complexity of the retinal microvasculature was associated with depression in older adults independent of potential confounding factors. Retinal measures may offer opportunistic assessment of microvascular health associated with outcomes of depression.

Association of retinal venular tortuosity with impaired renal function in the Northern Ireland Cohort for the Longitudinal Study of Ageing.

BACKGROUND: Previous studies have identified retinal microvascular features associated with renal dysfunction. Biopsies are necessary to confirm kidney microvascular damage and retinal imaging may enable evaluation of microangiopathic characteristics reflecting renal changes associated with chronic kidney disease (CKD). We evaluated retinal microvascular parameters (RMPs) for associations with renal function in a cross-sectional analysis of the Northern Ireland Cohort for the Longitudinal Study of Ageing. METHODS: RMPs (central retinal arteriolar/ venular equivalents [CRAE/CRVE], arteriolar to venular ratio [AVR], fractal dimension and tortuosity) were measured from optic disc centred fundus images using semi-automated software. Associations were assessed with multivariable regression analyses between RMPs and estimated glomerular filtration rate (eGFR) defined by serum creatinine (eGFRscr) and cystatin C (eGFRcys) and also CKD status characterised by eGFR < 60 mL/min/1.73m2. Regression models were adjusted for potential confounders including age, sex, diabetes, smoking status, educational attainment, cardiovascular disease, body mass index, antihypertensive medication, systolic blood pressure, triglycerides, high- and low-density lipoprotein levels. RESULTS: Data were included for 1860 participants that had measures of renal function and retinal fundus images of sufficient quality for analysis. Participants had a mean age of 62.0 ± 8.5 yrs. and 53% were female. The mean eGFR for scr and cys were 82.2 ± 14.9 mL/min/1.73m2 and 70.7 ± 18.6 mL/min/1.73m2 respectively. eGFRcys provided lower estimates than eGFRscr resulting in a greater proportion of participants categorised as having CKD stages 3-5 (eGFRcys 26.8%; eGFRscr 7.9%). Multivariable regression analyses showed that increased venular tortuosity (OR = 1.30; 95%CI: 1.10, 1.54; P < 0.01) was associated with CKD stages 3-5 characterised by eGFRscr < 60 mL/min/1.73 m2. No additional associations between CKD status characterised by eGFRscr or with eGFRcys, were detected (P > 0.05). Multivariable regression failed to detect associations between CRAE, CRVE, AVR, fractal dimension or tortuosity and eGFRscr or eGFRcys (P > 0.05). CONCLUSION: Increased retinal venular tortuosity was associated with CKD stages 3-5 defined by eGFRscr < 60 mL/min/1.73 m2, in an older population independent of potential confounding factors. These retinal measures may provide non-invasive microvascular assessment of associations with CKD.

Simple non-mydriatic retinal photography is feasible and demonstrates retinal microvascular dilation in Chronic Obstructive Pulmonary Disease (COPD).

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is associated with an increased risk of myocardial infarction and stroke but it remains unclear how to identify microvascular changes in this population. OBJECTIVES: We hypothesized that simple non-mydriatic retinal photography is feasible and can be used to assess microvascular damage in COPD. METHODS: Novel Vascular Manifestations of COPD was a prospective study comparing smokers with and without COPD, matched for age. Non-mydriatic, retinal fundus photographs were assessed using semi-automated software. RESULTS: Retinal images from 24 COPD and 22 control participants were compared. Cases were of similar age to controls (65.2 vs. 63.1 years, p = 0.38), had significantly lower Forced Expiratory Volume in one second (FEV1) (53.4 vs 100.1% predicted; p < 0.001) and smoked more than controls (41.7 vs. 29.6 pack years; p = 0.04). COPD participants had wider mean arteriolar (155.6 ±15 uM vs. controls [142.2 ± 12 uM]; p = 0.002) and venular diameters (216.8 ±20.7 uM vs. [201.3± 19.1 uM]; p = 0.012). Differences in retinal vessel caliber were independent of confounders, odds ratios (OR) = 1.08 (95% confidence intervals [CI] = 1.02, 1.13; p = 0.007) and OR = 1.05 (CI = 1.01, 1.09; p = 0.011) per uM increase in arteriolar and venular diameter respectively. FEV1 remained significantly associated with retinal vessel dilatation r = -0.39 (p = 0.02). CONCLUSIONS: Non-mydriatic retinal imaging is easily facilitated. We found significant arteriole and venous dilation in COPD compared to age-matched smokers without COPD associated with lung function independent of standard cardiovascular risk factors. Retinal microvascular changes are known to be strongly associated with future vascular events and retinal photography offers potential to identify this risk. TRIAL REGISTRATION: clinicaltrials.gov NCT02060292.

Distance to HIV care and treatment adherence: Adjusting for socio-demographic and geographical heterogeneity.

Distance to health services plays an important role in determining access to care and an individual's health. This study aims to examine the relationship between distance to antiretroviral therapy (ART) prescribing physician and adherence to HIV treatment in British Columbia, Canada. Only participants who provided highly accurate locational data for both place of residence and their physician were used in the analysis. Using logistic regression, a multivariable confounder model was created to assess the association between distance and adherence. A geographically weighted logistic regression was also performed to adjust for spatial dependency. There were 1528 participants in the analysis, for a median distance of 17.85km. The final model showed further away from ART prescribing physician had a higher chance of incomplete adherence to ART (adjusted odds ratio 1.31; 95% Confidence Interval 1.04-1.65). Mobile services could potentially increase adherence rates for population residing further away from their ART prescribing physician.

A tale of two countries: all-cause mortality among people living with HIV and receiving combination antiretroviral therapy in the UK and Canada.

OBJECTIVES: We sought to compare all-cause mortality of people living with HIV and accessing care in Canada and the UK. METHODS: Individuals from the Canadian Observational Cohort (CANOC) collaboration and UK Collaborative HIV Cohort (UK CHIC) study who were aged ≥ 18 years, had initiated antiretroviral therapy (ART) for the first time between 2000 and 2012 and who had acquired HIV through sexual transmission were included in the analysis. Cox regression was used to investigate the difference in mortality risk between the two cohort collaborations, accounting for loss to follow-up as a competing risk. RESULTS: A total of 19 960 participants were included in the analysis (CANOC, 4137; UK CHIC, 15 823). CANOC participants were more likely to be older [median age 39 years (interquartile range (IQR): 33, 46 years) vs. 36 years (IQR: 31, 43 years) for UK CHIC participants], to be male (86 vs. 73%, respectively), and to report men who have sex with men (MSM) sexual transmission risk (72 vs. 56%, respectively) (all P < 0.001). Overall, 762 deaths occurred during 98 798 person-years (PY) of follow-up, giving a crude mortality rate of 7.7 per 1000 PY [95% confidence interval (CI): 7.1, 8.3 per 1000 PY]. The crude mortality rates were 8.6 (95% CI: 7.4, 10.0) and 7.5 (95% CI: 6.9, 8.1) per 1000 PY among CANOC and UK CHIC study participants, respectively. No statistically significant difference in mortality risk was observed between the cohort collaborations in Cox regression accounting for loss to follow-up as a competing risk (adjusted hazard ratio 0.86; 95% CI: 0.72-1.03). CONCLUSIONS: Despite differences in national HIV care provision and treatment guidelines, mortality risk did not differ between CANOC and UK CHIC study participants who acquired HIV through sexual transmission.

An exploratory factor analysis of visual performance in a large population.

A factor analysis was performed on 25 visual and auditory performance measures from 1060 participants. The results revealed evidence both for a factor relating to general perceptual performance, and for eight independent factors that relate to particular perceptual skills. In an unrotated PCA, the general factor for perceptual performance accounted for 19.9% of the total variance in the 25 performance measures. Following varimax rotation, 8 consistent factors were identified, which appear to relate to (1) sensitivity to medium and high spatial frequencies, (2) auditory perceptual ability (3) oculomotor speed, (4) oculomotor control, (5) contrast sensitivity at low spatial frequencies, (6) stereo acuity, (7) letter recognition, and (8) flicker sensitivity. The results of a hierarchical cluster analysis were consistent with our rotated factor solution. We also report correlations between the eight performance factors and other (non-performance) measures of perception, demographic and anatomical measures, and questionnaire items probing other psychological variables.

Quality of initial HIV care in Canada: extension of a composite programmatic assessment tool for HIV therapy.

OBJECTIVES: To document the quality of initial HIV care in Canada using the Programmatic Compliance Score (PCS), to explore the association of the PCS with mortality, and to identify factors associated with higher quality of care. METHODS: We analysed data from the Canadian Observational Cohort Collaboration (CANOC), a multisite Canadian cohort of HIV-positive adults initiating combination antiretroviral therapy (ART) from 2000 to 2011. PCS indicators of noncompliance with HIV treatment guidelines include: fewer than three CD4 count tests in the first year of ART; fewer than three viral load tests in the first year of ART; no drug resistance testing before initiation; baseline CD4 count < 200 cells/mm3 ; starting a nonrecommended ART regimen; and not achieving viral suppression within 6 months of initiation. Indicators are summed for a score from 0 to 6; higher scores indicate poorer care. Cox regression was used to assess the association between PCS and mortality and ordinal logistic regression was used to explore factors associated with higher quality of care. RESULTS: Of the 7460 participants (18% female), the median score was 1.0 (Q1-Q3 1.0-2.0); 21% scored 0 and 8% scored ≥ 4. In multivariable analysis, compared with a score of 0, poorer PCS was associated with mortality for scores > 1 [score = 2: adjusted hazard ratio (AHR) 1.64; 95% confidence interval (CI) 1.13-2.36; score = 3: AHR 2.02; 95% CI 1.38-2.97; score ≥ 4: AHR 2.14; 95% CI 1.43-3.21], after adjustments for age, sex, province, ART start year, hepatitis C virus (HCV) coinfection, and baseline viral load. Women, individuals with HCV coinfection, younger people, and individuals starting ART earlier (2000-2003) had poorer scores. CONCLUSIONS: Our findings further validate the PCS as a predictor of all-cause mortality. Disparities identified suggest that further efforts are needed to ensure that care is equitably accessible.

Optimisation of photonic crystal coupling through waveguide design.

This paper considers multiple structural designs for photonic crystal surface emitting lasers operating at key wavelengths. Initially a structure from Williams et al. is modelled, the structure is modified to include an additional GaAs waveguide layer (termed ballast layer) and to include an additional PC layer (termed double decker). These structures are modelled by a combination of coupling calculation and waveguide modelling and are compared to the original structure. We show that both of these schemes give an increase in coupling, but present fabrication challenges. Next, we model standard laser structures operating at key wavelengths (400 nm, 1.3 and 10 µm) where a photonic crystal is located above the active region and explore the effect of increasing thickness of photonic crystal. We find that increasing the thickness increases the coupling coefficient but not true for the full range of thicknesses considered. This study allows a more universal comparison of the use of all-semiconductor, or void containing PCSELs to be conducted and we find that the realisation of all semiconductor PCSELs covering a wide range of material and wavelengths are possible.

Does age matter? Sexual event-level analysis of age-disparate sexual partners among gay, bisexual and other men who have sex with men (GBM) in Vancouver, Canada.

BACKGROUND: To determine factors associated with age-disparate sexual partners among Vancouver gay, bisexual and other men who have sex with men (GBM). METHODS: Sexually active GBM aged ≥16 years were recruited from February 2012 to February 2014. Participants self-completed a questionnaire on demographics, attitudes and sexual behaviour and substance use at last sexual event with five most recent partners. Two generalised linear mixed models identified factors associated with: (1) 'same-age' (referent), 'younger' or 'much-younger' and (2) 'same-age' (referent), 'older' or 'much-older' partners. Statistical interactions between age and HIV status were tested. RESULTS: Participants (n=719) were predominantly gay (85.1%), White (75.0%), HIV-negative/unknown status (72.9%) with median age of 33 years (Q1,Q3: 26,47). A minority of sexual events were reported with much-older/much-younger partners (13.7%). In the multivariable models, GBM reporting older partners were more likely to be Asian or Latino, have greater Escape Motivation scores, report their partner used erectile dysfunction drugs (EDDs) and have received something for sex; compared with condom-protected insertive anal sex, participants with older partners were more likely to report condomless insertive anal sex with a serodiscordant or unknown status partner or no insertive anal sex. GBM reporting older partners were less likely to be bisexual-identified, have given something for sex and report event-level alcohol and EDD use. GBM reporting younger partners were more likely to have annual incomes >$30 000 and have met their partner online. As per significant statistical interactions, age-disparate relations were more common for younger HIV-positive and older HIV-negative GBM. CONCLUSIONS: Differences among age-disparate partners highlight important targets for health promotion and future research.

Clinical features and long-term progression of reticular pseudodrusen in age-related macular degeneration: findings from a multicenter cohort.

PurposeTo determine whether reticular pseudodrusen (RPD) confer a long-term increased risk of progression to late age-related macular degeneration (AMD) in the fellow eye of patients with unilateral wet-AMD.Patients and methodsThis was a multicenter, combined prospective and retrospective, longitudinal, observational, study. Patients with wet-AMD in one eye were recruited from two centers and evaluated on the risk of progression to late-AMD in the second eye (study eye). A minimum follow-up of 5 years was required, unless progression occurred first. Baseline retinal profile of patients was evaluated using multimodal imaging. Baseline images were graded by two separate centers.ResultsWe recruited 88 patients (48 female) with a mean age of 75.6±7.1 years and mean follow-up of 65.7±20.9 months. Baseline prevalence of RPD was 58% (n=51). There was no statistically significant association of RPD with increased age (P=0.29) or sex distribution (P=0.39). The most sensitive image modality for RPD was IR (93%), followed by FAF (92%), OCT (74%, RF (33%) and CFP (29%). After 5 years, 54.50% (n=48) of the study eyes progressed to late-AMD. Of those, 81.25% (n=39) developed CNV and 18.75% (n=9) geographic atrophy. After correcting for age and sex, the presence of RPD was significantly associated with development of late-stage AMD (OR=2.55, P=0.03).ConclusionA multimodal approach is mandatory for RPD detection. RPD are highly prevalent in the fellow eyes of patients with unilateral neovascular AMD. Presence of RPD is associated with increased long-term risk of progression, highlighting the importance of comprehensive multimodal retinal imaging and careful monitoring of at-risk patients.

An integrated approach to care attracts people living with HIV who use illicit drugs in an urban centre with a concentrated HIV epidemic.

BACKGROUND: People living with HIV (PLHIV) who are also marginalized by social and structural inequities often face barriers to accessing and adhering to HIV treatment and care. The Dr. Peter Centre (DPC) is a non-profit integrated care facility with a supervised injection room that serves PLHIV experiencing multiple barriers to social and health services in Vancouver, Canada. This study examines whether the DPC is successful in drawing in PLHIV with complex health issues, including addiction. METHODS: Using data collected by the Longitudinal Investigations into Supportive and Ancillary health services (LISA) study from July 2007 to January 2010, linked with clinical variables available through the British Columbia Centre for Excellence in HIV/AIDS Drug Treatment Program, we identified DPC and non-DPC clients with a history of injection drug use. Bivariable and multivariable logistic regression analyses compared socio-demographic and clinical characteristics of DPC clients (n = 76) and non-DPC clients (n = 482) with a history of injection drug use. RESULTS: Of the 917 LISA participants included within this analysis, 100 (10.9%) reported being a DPC client, of which 76 reported a history of injection drug use. Adjusted results found that compared to non-DPC clients with a history of injection drug use, DPC-clients were more likely to be male (AOR: 4.18, 95% CI = 2.09-8.37); use supportive services daily vs. less than daily (AOR: 3.16, 95% CI = 1.79-5.61); to have been diagnosed with a mental health disorder (AOR: 2.11; 95% CI: 1.12-3.99); to have a history of interpersonal violence (AOR: 2.76; 95% CI: 1.23-6.19); and to have ever experienced ART interruption longer than 1 year (AOR: 2.39; 95% CI: 1.38-4.15). CONCLUSIONS: Our analyses suggest that the DPC operating care model engages PLHIV with complex care needs, highlighting that integrated care facilities are needed to support the multiple intersecting vulnerabilities faced by PLHIV with a history of injection drug use living within urban centres in North America and beyond.

Cost-effectiveness of community versus hospital eye service follow-up for patients with quiescent treated age-related macular degeneration alongside the ECHoES randomised trial.

OBJECTIVES: To assess the cost-effectiveness of optometrist-led follow-up monitoring reviews for patients with quiescent neovascular age-related macular degeneration (nAMD) in community settings (including high street opticians) compared with ophthalmologist-led reviews in hospitals. DESIGN: A model-based cost-effectiveness analysis with a 4-week time horizon, based on a 'virtual' non-inferiority randomised trial designed to emulate a parallel group design. SETTING: A virtual internet-based clinical assessment, conducted at community optometry practices, and hospital ophthalmology clinics. PARTICIPANTS: Ophthalmologists with experience in the age-related macular degeneration service; fully qualified optometrists not participating in nAMD shared care schemes. INTERVENTIONS: The participating optometrists and ophthalmologists classified lesions from vignettes and were asked to judge whether any retreatment was required. Vignettes comprised clinical information, colour fundus photographs and optical coherence tomography images. Participants' classifications were validated against experts' classifications (reference standard). Resource use and cost information were attributed to these retreatment decisions. MAIN OUTCOME MEASURES: Correct classification of whether further treatment is needed, compared with a reference standard. RESULTS: The mean cost per assessment, including the subsequent care pathway, was £411 for optometrists and £397 for ophthalmologists: a cost difference of £13 (95% CI -£18 to £45). Optometrists were non-inferior to ophthalmologists with respect to the overall percentage of lesions correctly assessed (difference -1.0%; 95% CI -4.5% to 2.5%). CONCLUSIONS: In the base case analysis, the slightly larger number of incorrect retreatment decisions by optometrists led to marginally and non-significantly higher costs. Sensitivity analyses that reflected different practices across eye hospitals indicate that shared care pathways between optometrists and ophthalmologists can be identified which may reduce demands on scant hospital resources, although in light of the uncertainty around differences in outcome and cost it remains unclear whether the differences between the 2 care pathways are significant in economic terms. TRIAL REGISTRATION NUMBER: ISRCTN07479761; Pre-results.

Awareness and use of nonoccupational post-exposure prophylaxis among men who have sex with men in Vancouver, Canada.

OBJECTIVES: Nonoccupational post-exposure prophylaxis (nPEP) is a strategy to reduce the risk of HIV infection in those with high-risk exposure. This study characterized nPEP awareness among gay, bisexual and other men who have sex with men (MSM) in Metro Vancouver, British Columbia, Canada after a pilot nPEP programme established in 2012. METHODS: Momentum Health Study participants were MSM aged ≥16 years recruited via respondent-driven sampling (RDS) who completed a computer-assisted self-interview. Stratifying patients by HIV status, we used multivariable logistic regression with backward selection to identify factors associated with nPEP awareness. All analyses were RDS-adjusted. RESULTS: A total of 51.9% (112 of 173) of HIV-positive and 48.5% (272 of 500) of HIV-negative participants had heard of nPEP. Only 3% (five of 106) of HIV-negative participants who reported recent high-risk sex used nPEP. Generally, nPEP awareness was higher for participants who engaged in sexual activities with increased HIV transmission potential. Factors associated with greater awareness among HIV-negative participants included recent alcohol use, higher communal sexual altruism, previous sexually transmitted infection diagnosis, and greater perceived condom use self-efficacy. Other factors associated with greater awareness among HIV-negative participants included white race/ethnicity, gay sexual identity, more formal education, lower personal sexual altruism, and Vancouver residence. Greater nPEP awareness among HIV-positive participants was associated with greater perceived agency to ask sexual partners' HIV status and more frequently reporting doing so, a higher number of lifetime receptive sex partners, and greater access to condoms. CONCLUSIONS: Following implementation of an nPEP pilot programme, nPEP awareness among HIV-negative MSM was 51% and use was 3%. These data support the need to expand access to and actively promote nPEP services.

Reductions in all-cause and cause-specific mortality among HIV-infected individuals receiving antiretroviral therapy in British Columbia, Canada: 2001-2012.

OBJECTIVES: Since 2006, the British Columbia HIV/AIDS Drug Treatment Program (DTP) has expanded enrolment and dramatically increased its number of participants. We examined the effect this expansion has had on the underlying cause of death in HIV-infected individuals. METHODS: We analysed data from participants aged 18 years and older in the DTP to measure 2-year mortality rates and causes of death from 2001 to 2012. We conducted tests of trend for all-cause and cause-specific mortality, and compared demographics and characteristics of individuals. Cox proportional hazard models were used to determine the risk of death. RESULTS: A total of 8185 participants received antiretroviral therapy (ART) during the study period. Mortality declined from 3.88 per 100 person-years (PY) in 2001-2002 to 2.15 per 100 PY in 2011-2012 (P = 0.02). There were significant decreases in HIV-related deaths (2.34 to 0.56 per 100 PY; P = 0.02) and deaths attributable to chronic liver disease (0.20 to 0.09 per 100 PY; P = 0.01), cardiovascular disease (0.24 to 0.05 per 100 PY; P = 0.03) and suicides (0.47 to 0 per 100 PY; P = 0.003). Multivariate models, adjusted for age, gender, history of injecting drug use, AIDS diagnoses and baseline CD4 cell counts, demonstrated that initiation of ART in all time periods after 2001-2002 was independently associated with reduced mortality (P < 0.001). CONCLUSIONS: We observed declines in HIV-related mortality and certain non-HIV-related causes of death among participants in the BC DTP from 2001 to 2012. These findings suggest that there may be broader benefits to the increasingly liberal HIV treatment guidelines, including reductions in death caused by cardiovascular disease and chronic liver disease.

10 GHz pulse repetition rate Er:Yb:glass laser modelocked with quantum dot semiconductor saturable absorber mirror.

Semiconductor saturable absorber mirror (SESAM) modelocked high pulse repetition rate (≥10 GHz) diode-pumped solid-state lasers are proven as an enabling technology for high data rate coherent communication systems owing to their low noise and high pulse-to-pulse optical phase-coherence. Compared to quantum well, quantum dot (QD)-based SESAMs offer potential advantages to such laser systems in terms of reduced saturation fluence, broader bandwidth, and wavelength flexibility. Here, we describe the first 10 GHz pulse repetition rate QD-SESAM modelocked laser at 1.55 µm, exhibiting 2 ps pulse width from an Er-doped glass oscillator (ERGO). The 10 GHz ERGO laser is modelocked with InAs/GaAs QD-SESAM with saturation fluence as low as 9 µJ/cm2.

STAT3 Activation in Circulating Monocytes Contributes to Neovascular Age-Related Macular Degeneration.

Infiltrating macrophages are critically involved in pathogenic angiogenesis such as neovascular agerelated macular degeneration (nAMD). Macrophages originate from circulating monocytes and three subtypes of monocyte exist in humans: classical (CD14(+)CD16(-)), non-classical (CD14(-)CD16(+)) and intermediate (CD14(+)CD16(+)) monocytes. The aim of this study was to investigate the role of circulating monocyte in neovascular age-related macular degeneration (nAMD). Flow cytometry analysis showed that the intermediate monocytes from nAMD patients expressed higher levels of CX3CR1 and HLA-DR compared to those from controls. Monocytes from nAMD patients expressed higher levels of phosphorylated Signal Transducer and Activator of Transcription 3 (pSTAT3), and produced higher amount of VEGF. In the mouse model of choroidal neovascularization (CNV), pSTAT3 expression was increased in the retina and RPE/choroid, and 49.24% of infiltrating macrophages express pSTAT3. Genetic deletion of the Suppressor of Cytokine Signalling 3 (SOCS3) in myeloid cells in the LysM-Cre(+/-):SOCS3(fl/fl) mice resulted in spontaneous STAT3 activation and accelerated CNV formation. Inhibition of STAT3 activation using a small peptide LLL12 suppressed laserinduced CNV. Our results suggest that monocytes, in particular the intermediate subset of monocytes are activated in nAMD patients. STAT3 activation in circulating monocytes may contribute to the development of choroidal neovascularisation in AMD.

The design and implementation of a study to investigate the effectiveness of community vs hospital eye service follow-up for patients with neovascular age-related macular degeneration with quiescent disease.

IntroductionStandard treatment for neovascular age-related macular degeneration (nAMD) is intravitreal injections of anti-VEGF drugs. Following multiple injections, nAMD lesions often become quiescent but there is a high risk of reactivation, and regular review by hospital ophthalmologists is the norm. The present trial examines the feasibility of community optometrists making lesion reactivation decisions.MethodsThe Effectiveness of Community vs Hospital Eye Service (ECHoES) trial is a virtual trial; lesion reactivation decisions were made about vignettes that comprised clinical data, colour fundus photographs, and optical coherence tomograms displayed on a web-based platform. Participants were either hospital ophthalmologists or community optometrists. All participants were provided with webinar training on the disease, its management, and assessment of the retinal imaging outputs. In a balanced design, 96 participants each assessed 42 vignettes; a total of 288 vignettes were assessed seven times by each professional group.The primary outcome is a participant's judgement of lesion reactivation compared with a reference standard. Secondary outcomes are the frequency of sight threatening errors; judgements about specific lesion components; participant-rated confidence in their decisions about the primary outcome; cost effectiveness of follow-up by optometrists rather than ophthalmologists.DiscussionThis trial addresses an important question for the NHS, namely whether, with appropriate training, community optometrists can make retreatment decisions for patients with nAMD to the same standard as hospital ophthalmologists. The trial employed a novel approach as participation was entirely through a web-based application; the trial required very few resources compared with those that would have been needed for a conventional randomised controlled clinical trial.