Routinized Syphilis Screening Among Men Living With Human Immunodeficiency Virus: A Stepped Wedge Cluster Randomized Controlled Trial.

BACKGROUND: We implemented an opt-out clinic-based intervention pairing syphilis tests with routine human immunodeficiency virus (HIV) viral load testing. The primary objective was to determine the degree to which this intervention increased the detection of early syphilis. METHODS: The Enhanced Syphilis Screening Among HIV-Positive Men (ESSAHM) Trial was a stepped wedge cluster-randomized controlled trial involving 4 urban HIV clinics in Ontario, Canada, from 2015 to 2017. The population was HIV-positive adult males. The intervention was standing orders for syphilis serological testing with viral loads, and control was usual practice. We obtained test results via linkage with the centralized provincial laboratory and defined cases using a standardized clinical worksheet and medical record review. We employed a generalized linear mixed model with a logit link to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of the intervention. RESULTS: A total of 3895 men were followed over 7471 person-years. The mean number of syphilis tests increased from 0.53 to 2.02 tests per person per year. There were 217 new diagnoses of syphilis (control, 81; intervention, 136), for which 147 (68%) were cases of early syphilis (control, 61 [75%]; intervention, 86 [63%]). The annualized proportion with newly detected early syphilis increased from 0.009 to 0.032 with implementation of the intervention; the corresponding time-adjusted OR was 1.25 (95% CI, .71-2.20). CONCLUSIONS: The implementation of standing orders for syphilis testing with HIV viral loads was feasible and increased testing, yet produced less-than-expected increases in case detection compared to past uncontrolled pre-post trials. CLINICAL TRIALS REGISTRATION: NCT02019043.

Hepatitis C virus testing in a clinical HIV cohort in Ontario, Canada, 2000 to 2015.

BACKGROUND: HIV-positive individuals may acquire HCV via injection drug use (IDU) and condomless anal sex. HIV care provides opportunities for HCV testing and cure with direct-acting antiviral agents (DAAs). METHODS: We analyzed data from the Ontario HIV Treatment Network Cohort Study. Among those not HCV-positive or diagnosed previously (n = 4586), we used Cox regression to test the rates of ever HCV testing (serological or RNA) in HIV care by DAA era (pre-DAA: 2000-2010; after DAA: 2011-2015) and compared the proportion diagnosed with HCV. We identified correlates of annual proportions of serological testing using Poisson generalized estimating equations. RESULTS: After DAA vs pre-DAA, the hazard rate ratio (95% CI) of ever HCV testing was 1.70 (1.59, 1.81). The proportion (95% CI) tested annually increased from 9.2% (8.0%, 10.7%) in 2000 to 39.1% (37.1%, 41.1%) in 2015 (P < 0.0001). The proportion diagnosed with HCV declined by 74% pre-DAA to 11% after DAAs. Annual testing increased per calendar year (16% steeper slope after DAA vs pre-DAA) and was more common among men who have sex with men; those more educated (post-secondary vs ≤ high school); and those positive for syphilis or reporting any IDU. Annual testing decreased per decade of age and time since HIV diagnosis. DISCUSSION: Annual HCV testing increased over time with higher testing among those reporting sexual or IDU risk factors, but fell short of clinical guidelines. Targeted interventions to boost testing may be needed to close these gaps and reach WHO 2030 HCV elimination targets.

Brief Report: Syphilis Coinfection Is Not Associated With an Increased Risk of Virologic Failure Among HIV-Positive Men Who Have Sex With Men on Antiretroviral Therapy.

BACKGROUND: Incidence of syphilis continues to increase among HIV-positive men who have sex with men (MSM) in Ontario. Our objective was to determine the effect of acute syphilis on virologic failure (VF) among virally suppressed HIV-positive MSM taking antiretroviral therapy (ART) and determine if the relationship is confounded by drug use. SETTING: The OHTN Cohort Study is a voluntary cohort of people receiving HIV care in Ontario. Syphilis and viral load (VL) data were retrieved via linkage with the provincial laboratory. METHODS: Analyses included 2632 MSM from 2008 to 2015, on ART, with ≥1 questionnaire and 2 consecutive VL of <50 copies per milliliter 6 months apart. VF was defined as (1) VL of ≥1000 copies per milliliter or (2) 2 consecutive VLs of ≥200 copies per milliliter ≥1 month apart. We modeled acute syphilis as a time-varying covariate on VF using Poisson regression. Time-varying drug use was assessed for confounding using an iterative process where potential confounders were removed and then reintroduced into the model. Our model allowed for repeat observations using generalized estimating equations. RESULTS: VF incidence was 3.5 per 100 person-years [95% confidence interval (CI): 3.4 to 4.2]. The rate ratio for VF for acute syphilis was 1.5 (95% CI: 0.9 to 2.4) in the unadjusted model; 1.6 (95% CI: 1.0 to 2.4) in the model adjusted for age, education, region, and income; and 1.2 (95% CI: 0.7 to 1.9) in the final model with additional adjustment for drug use. CONCLUSIONS: Acute syphilis was not associated with VF among virologically suppressed MSM on ART. Consequently, ART may still reduce HIV transmission risk to sexual partners.

Enhanced syphilis screening among HIV-positive men (ESSAHM): a study protocol for a clinic-randomized trial with stepped wedge design.

BACKGROUND: The current syphilis epidemic among urban men who have sex with men (MSM) has serious implications for those co-infected with human immunodeficiency virus (HIV). Routine and frequent syphilis screening has the potential to ensure early detection and treatment, minimize disease burden, and help control the ongoing spread of syphilis and HIV. We aim to enhance syphilis screening among HIV-positive men by conducting a clinic-based intervention that incorporates opt-out syphilis testing into routine HIV laboratory evaluation for this population. Trial objectives are to determine the degree to which the intervention (1) increases the detection rate of untreated syphilis, (2) increases screening coverage, (3) increases screening frequency, and (4) reaches men at highest risk according to sexual behaviors. METHODS/DESIGN: The trial is a pragmatic, stepped wedge cluster-randomized controlled trial that introduces the intervention stepwise across four urban HIV clinics in Ontario, Canada. The intervention includes standing orders for syphilis serological testing whenever a male in HIV care undergoes HIV viral load testing, which typically occurs every 3-6 months. The control condition is the maintenance of current, provider-initiated syphilis testing practice. Approximately 3100 HIV-positive men will be followed over 30 months. Test results will be obtained from the centralized provincial laboratory in Ontario and will be supplemented by a standardized clinical worksheet and medical chart review at the clinics. Detailed clinical, psychosocial, and behavioral data is available for a subset of men receiving HIV care who are also participants of the province-wide Ontario HIV Treatment Network Cohort Study. Process evaluation plans include audit and feedback of compliance of the participating centers to identify potential barriers to the introduction of this type of practice into routine care. Health economic components include evaluation of the impact and cost-effectiveness of the intervention. DISCUSSION: This trial will be the first of its kind in Canada and will provide evidence regarding the feasibility, clinical effectiveness, and cost-effectiveness of a clinic-based intervention to improve syphilis screening among HIV-positive men. Involvement of knowledge users in all stages of trial design, conduct, and analysis will facilitate scale-up should the intervention be effective. TRIAL REGISTRATION: ClinicalTrials.gov NCT02019043.

High incidence of diagnosis with syphilis co-infection among men who have sex with men in an HIV cohort in Ontario, Canada.

BACKGROUND: The re-emergence of syphilis among HIV-positive gay and other men who have sex with men (MSM) requires vigilance. We estimated incidence of and risk factors for first and subsequent syphilis diagnoses among MSM in HIV care in Ontario, Canada. METHODS: We analyzed data from 2,280 MSM under follow-up from 2006 to 2010 in the Ontario HIV Treatment Network Cohort Study (OCS), a multi-site clinical cohort. We obtained syphilis serology results via record linkage with the provincial public health laboratory. Rates were calculated using Poisson regression. RESULTS: First syphilis diagnoses occurred at a rate of 2.0 per 100 person-years (95 % CI 1.7, 2.4; 121 cases) whereas the re-diagnosis rate was 7.5 per 100 person-years (95 % CI 6.3, 8.8; 136 cases). We observed higher rates over time and among men who were aged <30 years, receiving care in the two largest urban centers, or had a previous syphilis diagnosis. Syphilis diagnosis was less common among Indigenous men, men with higher CD4 cell counts, and, for first diagnoses only, among men with less than high school education. CONCLUSIONS: Compared to reported cases in the general male population, incidence of a new syphilis diagnosis was over 300 times greater among HIV-positive MSM but year-to-year changes reflected provincial trends. Re-diagnosis was common, suggesting treatment failure or re-infection. Novel syphilis control efforts are needed among HIV-positive MSM.

Hepatitis C virus seroconversion among HIV-positive men who have sex with men with no history of injection drug use: Results from a clinical HIV cohort.

BACKGROUND: Internationally, there is a growing recognition that hepatitis C virus (HCV) may be sexually transmitted among HIV-positive men who have sex with men (MSM). OBJECTIVE: To report the first Canadian estimate of HCV seroincidence in 2000 to 2010 and its risk factors among HIV-positive MSM with no known history of injection drug use. METHODS: Data from the Ontario HIV Treatment Network Cohort Study, an ongoing cohort of individuals in HIV care in Ontario, were analyzed. Data were obtained from medical charts, interviews and record linkage with the provincial public health laboratories. The analysis was restricted to 1534 MSM who did not report injection drug use and had undergone ≥2 HCV antibody tests, of which the first was negative (median 6.1 person-years [PY] of follow-up; sum 9987 PY). RESULTS: In 2000 to 2010, 51 HCV seroconversions were observed, an overall incidence of 5.1 per 1000 PY (95% CI 3.9 to 6.7). Annual incidence varied from 1.6 to 8.9 per 1000 PY, with no statistical evidence of a temporal trend. Risk for seroconversion was elevated among men who had ever had syphilis (adjusted HR 2.5 [95% CI 1.1 to 5.5) and men who had acute syphilis infection in the previous 18 months (adjusted HR 2.8 [95% CI 1.0 to 7.9]). Risk was lower for men who had initiated antiretroviral treatment (adjusted HR 0.49 [95% CI 0.25 to 0.95]). There were no statistically significant effects of age, ethnicity, region, CD4 cell count or HIV viral load. CONCLUSIONS: These findings suggest that periodic HCV rescreening may be appropriate in Ontario among HIV-positive MSM. Future research should seek evidence whether syphilis is simply a marker for high-risk sexual behaviour or networks, or whether it potentiates sexual HCV transmission among individuals with HIV.

HISTORIQUE: Sur la scène internationale, il apparaît de plus en plus clairement que le virus de l'hépatite C (VHC) peut être transmis sexuellement entre hommes positifs au VIH ayant des relations sexuelles avec des hommes (HARSAH). OBJECTIF: Rendre compte de la première estimation canadienne de la séro-incidence de VHC entre 2000 et 2010 et de ses facteurs de risque chez les HARSAH positifs au VIH sans antécédents connus de consommation de drogues injectables. MÉTHODOLOGIE: Les chercheurs ont analysé les données de l'Ontario HIV Treatment Network Cohort Study, une cohorte continue de personnes soignées pour le VIH en Ontario. Ils ont tiré les données de dossiers médicaux, d'entrevues et de liens entre les dossiers et les laboratoires provinciaux de santé publique. Ils ont restreint l'analyse à 1 534 HARSAH qui ne déclaraient pas consommer de drogues injectables et qui avaient subi au moins deux tests d'anticorps du VHC, dont le premier était négatif (suivi médian de 6,1 années-personne [AP]; somme de 9 987 AP). RÉSULTATS: De 2000 à 2010, les chercheurs ont observé 51 cas de séroconversion au VHC, pour une incidence globale de 5,1 cas sur 1 000 AP (95 % IC 3,9 à 6,7). L'incidence annuelle variait entre 1,6 et 8,9 cas sur 1 000 AP, sans preuve statistique de tendance temporelle. Le risque de séroconversion était élevé chez les hommes qui n'avaient jamais eu la syphilis (RR rajusté 2,5 [95 % IC 1,1 à 5,5) et chez les hommes qui avaient eu une infection aiguë par la syphilis dans les 18 mois précédents (RR rajusté 2,8 [95 % IC 1,0 à 7,9]). Le risque était plus faible chez les hommes qui avaient entrepris un traitement anti-rétroviral (RR rajusté 0,49 [95 % IC 0,25 à 0,95]). L'âge, l'ethnie, la région, la numération des cellules CD4 et la charge virale du VIH n'avaient pas d'effet statistiquement significatif. CONCLUSIONS: D'après ces observations, il serait judicieux de procéder au dépistage périodique du VHC chez les HARSAH positifs au VIH de l'Ontario. De prochaines recherches devraient viser à établir si la syphilis est un simple marqueur de comportements ou de réseaux sexuels à haut risque ou si elle potentialise la transmission sexuelle du VHC chez les personnes atteintes du VIH.

Modest rise in chlamydia and gonorrhoea testing did not increase case detection in a clinical HIV cohort in Ontario, Canada.

OBJECTIVES: We described patterns of testing for chlamydia and gonorrhoea infection among persons in specialty HIV care in Ontario, Canada, from 2008 to 2011. METHODS: We analysed data from 3165 participants in the OHTN Cohort Study attending one of seven specialty HIV care clinics. We obtained chlamydia and gonorrhoea test results via record linkage with the provincial public health laboratory. We estimated the proportion of participants who underwent testing annually, the positivity rate among those tested and the proportion diagnosed with chlamydia or gonorrhoea among all under observation. We explored risk factors for testing and diagnosis using multiple logistic regression analysis. RESULTS: The proportion tested annually rose from 15.2% (95% CI 13.6% to 16.7%) in 2008 to 27.0% (95% CI 25.3% to 28.6%) in 2011 (p<0.0001). Virtually all were urine-based nucleic acid amplification tests. Testing was more common among men who have sex with men (MSM), younger adults, Toronto residents, persons attending primary care clinics and persons who had tested in the previous year or who had more clinic visits in the current year. We observed a decrease in test positivity rates over time. However, the annual proportion diagnosed remained stable and in 2011 this was 0.97% (95% CI 0.61% to 1.3%) and 0.79% (95% CI 0.46% to 1.1%) for chlamydia and gonorrhoea, respectively. Virtually all cases were among MSM. CONCLUSIONS: Chlamydia and gonorrhoea testing increased over time while test positivity rates declined and the overall proportion diagnosed remained stable, suggesting that the modest increase in testing did not improve case detection.

Early expansion of the intracranial CSF volume after palliative whole-brain radiotherapy: results of a longitudinal CT segmentation analysis.

PURPOSE: To assess cerebral atrophy after radiotherapy, we measured intracranial cerebrospinal fluid volume (ICSFV) over time after whole-brain radiotherapy (WBRT) and compared it with published normal-population data. METHODS AND MATERIALS: We identified 9 patients receiving a single course of WBRT (30 Gy in 10 fractions over 2 weeks) for ipsilateral brain metastases with at least 3 years of computed tomography follow-up. Segmentation analysis was confined to the tumor-free hemi-cranium. The technique was semiautomated by use of thresholds based on scanned image intensity. The ICSFV percentage (ratio of ICSFV to brain volume) was used for modeling purposes. Published normal-population ICSFV percentages as a function of age were used as a control. A repeated-measures model with cross-sectional (between individuals) and longitudinal (within individuals) quadratic components was fitted to the collected data. The influence of clinical factors including the use of subependymal plate shielding was studied. RESULTS: The median imaging follow-up was 6.25 years. There was an immediate increase (p < 0.0001) in ICSFV percentage, which decelerated over time. The clinical factors studied had no significant effect on the model. CONCLUSIONS: WBRT immediately accelerates the rate of brain atrophy. This longitudinal study in patients with brain metastases provides a baseline against which the potential benefits of more localized radiotherapeutic techniques such as radiosurgery may be compared.

Sepsis in the neonate.

In the neonatal intensive care unit, critical care nurses who are not advanced practice nurses cannot make the medical diagnosis of infection/sepsis in the neonate. Even so, the critical care nurse has a critical role in dealing with sepsis infection. The nurse must (1) have a high index of suspicion about the risk of infection, (2) be able to recognize septic/infected newborns, (3) report related concerns to the physician or advanced practice nurse, and (4) advocate on behalf of the infant to ensure a timely diagnostic workup and empiric antibiotics. This article is a guide for understanding issues related to sepsis in the neonatal intensive care unit.

Testosterone recovery after prolonged androgen suppression in patients with prostate cancer.

PURPOSE: We prospectively examined the extent and timing of testosterone recovery in patients with prostate cancer treated with 2 years of androgen suppression. MATERIALS AND METHODS: A total of 153 patients with pT3N0M0 prostate cancer or positive margins after radical prostatectomy, or with prostate specific antigen relapse were treated with radiation to the prostate bed plus 2 years of androgen suppression as per a phase II study. Androgen suppression consisted of nilutamide for 4 weeks plus busereline acetate bimonthly for 2 years. Serum testosterone was measured at baseline, every 4 months during androgen suppression and every 6 months after androgen suppression during followup. Testosterone recovery to supracastrate levels, and to baseline and/or normal levels was estimated using Kaplan-Meier methods. Prognostic factors for testosterone recovery were examined. RESULTS: A total of 121 patients who completed 2 years of androgen suppression and 20 patients who received shorter durations of androgen suppression (median 16 months) were available for testosterone recovery analysis. Median followup after finishing androgen suppression was 38.9 months. All patients achieved castrate levels on androgen suppression. At 36 months after completion of androgen suppression 93.2% and 71.5% had recovery to supracastrate (median time 12.7 months), and to baseline and/or normal testosterone levels (median time 22.3 months), respectively. On multivariate analysis younger age (younger than 60 years, p = 0.0006) and shorter androgen suppression duration (less than 2 years, p = 0.028) were prognostic for faster recovery to baseline and/or normal testosterone levels after adjusting for baseline testosterone levels (p = 0.447). CONCLUSIONS: Testosterone recovery after prolonged androgen suppression is protracted. Older age and longer duration of androgen suppression result in significantly longer recovery times to baseline and/or normal testosterone levels.