Belatacept for Simultaneous Calcineurin Inhibitor and Chronic Corticosteroid Immunosuppression Avoidance: Two-Year Results of a Prospective, Randomized Multicenter Trial.

BACKGROUND AND OBJECTIVES: Immunosuppressive therapy in kidney transplantation is associated with numerous toxicities. CD28-mediated T-cell costimulation blockade using belatacept may reduce long-term nephrotoxicity, compared with calcineurin inhibitor-based immunosuppression. The efficacy and safety of simultaneous calcineurin inhibitor avoidance and rapid steroid withdrawal were tested in a randomized, prospective, multicenter study. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study reports the 2-year results of a randomized clinical trial of 316 recipients of a new kidney transplant. All kidney transplants were performed using rapid steroid withdrawal immunosuppression. Recipients were randomized in a 1:1:1 ratio to receive belatacept with alemtuzumab induction, belatacept with rabbit anti-thymocyte globulin (rATG) induction, or tacrolimus with rATG induction. The composite end point consisted of death, kidney allograft loss, or an eGFR of <45 ml/min per 1.73 m2 at 2 years. RESULTS: The composite end point was observed for 11 of 107 (10%) participants assigned to belatacept/alemtuzumab, 13 of 104 (13%) participants assigned to belatacept/rATG, and 21 of 105 (21%) participants assigned to tacrolimus/rATG (for belatacept/alemtuzumab versus tacrolimus/rATG, P=0.99; for belatacept/rATG versus tacrolimus/rATG, P=0.66). Patient and graft survival rates were similar between all groups. An eGFR of <45 ml/min per 1.73 m2 was observed for nine of 107 (8%) participants assigned to belatacept/alemtuzuab, eight of 104 (8%) participants assigned to belatacept/rATG, and 20 of 105 (19%) participants assigned to tacrolimus/rATG (P<0.05 for each belatacept group versus tacrolimus/rATG). Biopsy sample-proven acute rejection was observed for 20 of 107 (19%) participants assigned to belatacept/alemtuzuab, 26 of 104 (25%) participants assigned to belatacept/rATG, and seven of 105 (7%) participants assigned to tacrolimus/rATG (for belatacept/alemtuzumab versus tacrolimus/rATG, P=0.006; for belatacept/rATG versus tacrolimus/rATG, P<0.001). Gastrointestinal and neurologic adverse events were less frequent with belatacept versus calcineurin-based immunosuppression. CONCLUSIONS: Overall 2-year outcomes were similar when comparing maintenance immunosuppression using belatacept versus tacrolimus, and each protocol involved rapid steroid withdrawal. The incidence of an eGFR of <45 ml/min per 1.73 m2 was significantly lower with belatacept compared with tacrolimus, but the incidence of biopsy sample-proven acute rejection significantly higher. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Belatacept Early Steroid Withdrawal Trial, NCT01729494.

Implementation and evaluation of a culturally grounded group-based HIV prevention programme for men who have sex with men in Ghana.

This study examined the feasibility and acceptability of an evidence-based HIV prevention programme for men who have sex with men (MSM) in Ghana through a participatory approach. The programme involved 57 self-identified adult cisgender MSM and led by a community-based organisation in collaboration with local nurses. We used an explanatory mixed-method design to evaluate the programme. We computed descriptive statistics, relative frequency, and paired proportionate analysis for the survey data and subjected the focus groups data to summative content analysis. Five key themes from the qualitative data indicated strong evidence of the acceptability and efficacy of the programme among MSM. The programme contributed to building social support networks, a sense of social justice among MSM, and facilitated the development of personalised HIV prevention menus by the participants. We observed increases in HIV testing (from 4% to 17%) and increases in the relative frequency of condom use for anal, oral, and vaginal sex. The programme served as an example of a successfully implemented culturally grounded intervention that has the potential to increase HIV and STI awareness and prevention among MSM in Ghana and other highly stigmatised environments.

Social, Clinical, and Behavioral Determinants of HIV Infection and HIV Testing among Black Men in Toronto, Ontario: A Classification and Regression Tree Analysis.

Black men bear a disproportionate burden of HIV infection. These HIV inequities are influenced by intersecting social, clinical, and behavioral factors. The purpose of this analysis was to determine the combinations of factors that were most predictive of HIV infection and HIV testing among black men in Toronto. Classification and regression tree analysis was applied to secondary data collected from black men (N = 460) in Toronto, 82% of whom only had sex with women and 18% whom had sex with men at least once. For HIV infection, 10 subgroups were identified and characterized by number of lifetime male partners, age, syphilis history, and perceived stigma. Number of lifetime male partners was the best single predictor of HIV infection. For HIV testing, the analysis identified 8 subgroups characterized by age, condom use, number of sex partners and Chlamydia history. Age (>24 years old) was the best single predictor of HIV testing.

Belatacept-based immunosuppression with simultaneous calcineurin inhibitor avoidance and early corticosteroid withdrawal: A prospective, randomized multicenter trial.

Simultaneous calcineurin inhibitor avoidance (CNIA) and early corticosteroid withdrawal (ESW) have not been achieved primarily due to excessive acute rejection. This trial compared 2 belatacept-based CNIA/ESW regimens with a tacrolimus-based ESW regimen. Kidney transplant recipients were randomized to receive alemtuzumab/belatacept, rabbit anti-thymocyte globulin (rATG)/belatacept, or rATG/tacrolimus. The combinatorial primary endpoint consisted of patient death, renal allograft loss, or a Modification of Diet in Renal Disease-calculated eGFR of <45 mL/min/1.73 m2 at 12 months. Results are reported by treatment group (alemtuzumab/belatacept, rATG/belatacept, and rATG/tacrolimus). Superiority was not observed at 1 year for the primary endpoint (9/107 [8.4%], 15/104 [14.4%], and 14/105 [13.3%], respectively; P = NS) for either belatacept-based regimen. Differences were not observed for secondary endpoints (death, death-censored graft loss, or estimated glomerular filtration rates < 45 mL/min/1.73 m2 ). Differences were observed in biopsy-proved acute cellular rejection (10.3%, 18.3%, and 1.9%, respectively) (P < .001), but not in antibody-mediated rejection, mixed acute rejection, or de novo donor-specific anti-HLA antibodies. Neurologic and electrolyte abnormality adverse events were less frequent under belatacept. Belatacept-based CNIA/ESW regimens did not prove to be superior for the primary or secondary endpoints. Belatacept-treated patients demonstrated an increase in biopsy-proved acute cellular rejection and reduced neurologic and metabolic adverse events. These results demonstrate that simultaneous CNIA/ESW is feasible without excessive acute rejection.

Effectiveness of long-term infliximab use and impact of treatment adherence on disease control in refractory, non-infectious pediatric uveitis.

BACKGROUND: Refractory non-infectious uveitis is a serious condition that leads to ocular complications and vision loss and requires effective systemic treatment to control disease. The effectiveness of long-term infliximab [IFX] in refractory non-infectious childhood uveitis and the impact of treatment adherence on disease control were evaluated. METHODS: Retrospective, single-center study between December 2002 and April 2016 of 27 children with refractory non-infectious uveitis [17 with juvenile idiopathic arthritis, JIA] treated with long-term IFX [9+ months]. Disease activity was assessed prior to and while on IFX using the Standardization of Uveitis Nomenclature [SUN]. Number of visits per year with active uveitis was analyzed by repeated measures logistic regression analysis from 2 years prior to IFX initiation or from onset of uveitis until most recent visit on IFX. Incomplete treatment adherence was assessed for each visit and defined as any deviance in corticosteroid use, prescribed infusion frequency, and/or follow-up examination frequency. RESULTS: Primary outcomes were sustained uveitic and systemic disease control prior to and during IFX treatment and the impact of incomplete adherence on uveitic disease control while on IFX. Secondary outcomes included corticosteroid and glaucoma medication requirement, ocular complications and need for surgical intervention. Mean age at IFX initiation was 10.4 ± 4.5 years; initial mean dose was 6.6 ± 2.2 mg/kg [and given at weeks 0, 2, 4 and q4 weeks thereafter for 93%]. Median duration on IFX was 35 [range 9-128] months. Prior to IFX, 14/27 patients had failed adalimumab ± methotrexate [MTX]; 21/27 failed MTX. IFX led to uveitis control in 89% and arthritis control in 76% (13/17). The odds ratio of having controlled disease after IFX was 4.1 (2.6, 6.4) compared to pre-treatment visits. Topical corticosteroids and glaucoma medications were statistically decreased (p = 0.007 right eye [OD], 0.003 left eye [OS] and p = 0.001 OD, p = 0.028 OS respectively). Incomplete adherence to treatment showed 10.3 times greater odds (7.1, 15.0) of having disease activity than full adherence. CONCLUSIONS: This study adds significantly to the IFX literature by documenting outstanding uveitis control with long-term IFX treatment in non-infectious pediatric uveitis patients. Higher dosage and shorter interval were utilized without adverse effects. Importantly, this is the first study, to our knowledge, to document the significant impact of treatment adherence on uveitis control.

Barriers to HIV pre-exposure prophylaxis among African, Caribbean and Black men in Toronto, Canada.

INTRODUCTION: Single-tablet combination emtricitabine/tenofovir is highly effective as HIV pre-exposure prophylaxis (PrEP). Scale-up efforts have targeted men who have sex with men (MSM), but patterns of racial disparities in PrEP use have begun to emerge. African, Caribbean and Black (ACB) communities in Canada and USA are also disproportionately affected by HIV, and there is lack of guidance regarding PrEP implementation in this priority population. METHODS: ACB men from Toronto, Canada were recruited in community settings by peers. Participants completed a detailed socio-behavioural questionnaire. Biological samples were collected and tested for sexually transmitted infections. Willingness to accept PrEP was assessed in relation to actual and self-perceived risk of acquiring HIV, as well as demographic and behavioural variables. RESULTS: 424 ACB men were included in the analysis. ACB MSM were more likely to accept PrEP than ACB men only reporting sex with women (MSW; 50.0% vs. 23.6%). The most common reasons for PrEP non-acceptance were concerns regarding side-effects and low self-perceived risk. PrEP acceptance was lowest among younger men (12.5%) and those born in Canada (15.2%). Men with a high self-perceived HIV risk were more likely to accept PrEP (41.3% vs. 22.7% of men with a low self-perceived risk), but only 25.4% of men who were defined as being at high-risk, self-identified themselves as such. CONCLUSIONS: Most ACB MSW were unlikely to accept PrEP, largely due to low self-perceived HIV risk, but PrEP acceptance among ACB MSM was similar to other contemporaneous Toronto MSM communities. PrEP acceptance was particularly low among younger ACB men and those born in Canada. Tailored strategies will be needed to effectively implement PrEP in Toronto ACB communities.

The epidemiology of HIV and other sexually transmitted infections in African, Caribbean and Black men in Toronto, Canada.

BACKGROUND: African, Caribbean, and Black (Black) men account for 16.5% of new HIV diagnoses among men in Ontario. There is substantial evidence that sexually transmitted infections (STIs) are associated with increased likelihood of HIV infection; however, little is known regarding the prevalence of HIV/STI co-infections among Black men in Toronto. Progress has been made in understanding factors contributing to racial/ethnic disparities in HIV between among men who have sex with men (MSM). In this study, we investigate within-racial group patterns of HIV/STI infection between Black MSM and Black men who only have sex with women (MSW). METHODS: A cross-sectional descriptive epidemiological study was conducted with a non-probability sample of Black men recruited from Toronto, Ontario. Audio Computer Assisted Self-Interviews (ACASI) surveys were used to collect demographic and behavioral data. Biological specimens were collected to screen for HIV and other STIs. Chi-Square tests were used to compare the prevalence of (1) HIV and current STIs between MSM and MSW and (2) current STIs between people living with HIV and people not living with HIV. Logistic regression models were constructed to assess whether or not history of STIs were associated with current HIV infection. RESULTS: The prevalence of HIV (9.2%), syphilis (7.2%), hepatitis B (2.7%), and high-risk anal HPV (8.4%) and penile HPV (21.3%) infections were high in Black men (N = 487) and were significantly increased in Black MSM compared with MSW; the prevalence of syphilis and high-risk HPV were also increased in men living with HIV. Men with a history of syphilis (OR = 6.48, 95% CI: 2.68,15.71), genital warts (OR = 4.32, 95% CI: 1.79,10.43) or genital ulcers (OR = 21.3, 95% CI: 1.89,239.51) had an increased odds of HIV infection. CONCLUSIONS: The HIV/STI prevalence was high among this sample of Black men, although the study design may have led to oversampling of men living with HIV. The associations between STIs and current HIV infection highlight the need for integrated of HIV/STI screening and treatment programs for Black men. Public health strategies are also needed to reduce disproportionate HIV/STI burden among Black MSM-including improving HPV vaccine coverage.

Participation in Home Visitation is Associated with Higher Utilization of Early Intervention.

Objectives To determine whether participation in a home visiting program increases and expedites utilization of early intervention services for suspected developmental delays. Methods Children participating in Every Child Succeeds (ECS), a large home visiting (HV) program serving greater Cincinnati, between 2006 and 2012, were propensity score matched to a sample of children identified from birth records who did not receive services from ECS. Data were linked to early intervention (EI) data acquired from the Ohio Department of Health. Descriptive statistics were employed to evaluate success of the matching. Chi square and log-rank tests evaluated whether the proportion of children accessing EI and the time to EI services differed for families participating in HV compared to eligible children not participating. Logistic regression and Cox proportional hazards regression modeled the associations. Results Among 3574 HV and 3574 comparison participants, there was no difference in the time to EI service utilization; however a higher percentage of HV participants accessed services. Overall, 6% of the HV group and 4.3% of the comparison group accessed services (p = 0.001). Modeling revealed an odd ratio = 1.43 [95% confidence interval (CI) 1.16-1.78, p value = 0.001] and hazard ratio = 1.42 [95% CI 1.15-1.75, p value = 0.001]. Differences in utilization were greatest directly after birth and between approximately 2 and 3 years. Conclusions for Practise Participation in home visiting was associated with greater utilization of EI services during two important developmental time points, demonstrating that home visiting may serve as an important resource for facilitating access to early intervention services.

Maternal Interpersonal Trauma and Child Social-Emotional Development: An Intergenerational Effect.

BACKGROUND: Evidence suggests that maternal interpersonal trauma can adversely affect offspring health, but little is known about potential transmission pathways. We investigated whether interpersonal trauma exposure had direct and indirect associations with offspring social-emotional development at 12-months of age in an at-risk, home visited population. METHODS: A retrospective cohort study was conducted of 1172 mother-child dyads who participated in a multi-site, early childhood home visiting program. Children were born January 2007 to June 2010 and data were collected at enrolment (prenatal/birth) through 12-months of age. Multivariable path analyses were used to examine the relationship between maternal interpersonal trauma, subsequent psychosocial mediators (maternal depressive symptoms, social support, and home environment), and the outcome of child social-emotional development measured with the Ages and Stages Questionnaire: Social-Emotional (ASQ:SE). Maternal interpersonal trauma was characterized as any previous exposure, the level of exposure, and type (e.g. abuse) of exposure. RESULTS: The prevalence of maternal interpersonal trauma exposure was 69.1%, and exposures ranged from 1 type (19.3%) to 7 types (2.3%). Interpersonal trauma was associated with a 3.6 point (95% confidence interval 1.8, 5.4) higher ASQ:SE score among offspring and indicated greater developmental risk. An estimated 23.4% of the total effect was mediated by increased maternal depressive symptoms and lower social support. Differential effects were observed by the level and type of interpersonal trauma exposure. CONCLUSION: Maternal interpersonal trauma exposures can negatively impact child social-emotional development, acting in part through maternal psychosocial factors. Future research is needed to further elucidate the mechanisms of intergenerational risk.

Evaluation of Early Childhood Home Visiting to Prevent Medically Attended Unintentional Injury.

STUDY OBJECTIVE: We evaluated the influence of home visiting on the risk for medically attended unintentional injury during home visiting (0 to 3 years) and subsequent to home visiting (3 to 5 years). METHODS: A retrospective, quasi-experimental study was conducted in a cohort of mother-child pairs in Hamilton County, OH. The birth cohort (2006 to 2012) was linked to administrative home visiting records and data from a population-based injury surveillance system containing records of emergency department (ED) visits and hospitalizations. Cox proportional-hazard regression was used to compare medically attended unintentional injury risk (0 to 2, 0 to 3, and 3 to 5 years) in a home-visited group versus a propensity score-matched comparison group. The study population was composed of 2,729 mother-child pairs who received home visiting and 2,729 matched mother-child pairs in a comparison group. RESULTS: From birth to 2 years, 17.2% of the study population had at least one medically attended unintentional injury. The risk for medically attended unintentional injury from aged 0 to 2 and 0 to 3 years was significantly higher in the home-visited group relative to the comparison group (hazard ratio 1.17, 95% confidence interval 1.01 to 1.35; hazard ratio 1.15, 95% confidence interval 1.00 to 1.31, respectively). Additional injuries in the home-visited group were superficial, and the increased risk for medically attended unintentional injury was observed for ED visits and not hospitalizations. CONCLUSION: Home-visited children were more likely to have a medically attended unintentional injury from birth to aged 3 years. This finding may be partially attributed to home visitor surveillance of injuries or greater health care-seeking behavior. Implications and alternative explanations are discussed.

Temporal trends in inpatient pediatric sleep apnea surgery: 1993-2010.

OBJECTIVES/HYPOTHESIS: We sought to characterize changes in the patterns of inpatient surgical sleep care over time and ascertain if these changes were consistent with previously reported trends in adult surgical sleep care. STUDY DESIGN: Repeated cross-sectional study. METHODS: Discharge data from the U.S. Nationwide Inpatient Sample for 125,691 nasal, palatal, or hypopharyngeal procedures in children for sleep-disordered breathing or obstructive sleep apnea (OSA) from 1993 to 2010 were analyzed using cross-tabulations and multivariate regression modeling. RESULTS: Inpatient surgical sleep procedures increased from 45,671 performed in 1993 to 2000 (study period 1) to 80,020 in 2001 to 2010 (study period 2). Overall, patients were commonly male (61.3%), privately insured (46.8%), 2 to 6 years old (39.4%), and white (36.4%). Obesity was reported in 4.6% and 6.7% of children during study periods 1 and 2, respectively (P < .0001). Tonsillectomy (with and without adenoidectomy) was the most commonly performed procedure in both study periods. With the exception of uvulopalatopharyngoplasty and tracheostomy, all sleep procedures increased over time; however, multilevel surgery did not significantly increase (P = .28). Children who underwent sleep surgery during study period 2 were more likely to receive a supraglottoplasty (P = .0125) and to undergo procedures at high-volume hospitals (P = .0311), and less likely to undergo a tracheostomy (P < .0001). CONCLUSIONS: These data reflect changing trends in the surgical management of pediatric OSA, with significant increases in nasal and hypopharyngeal procedures, particularly lingual tonsillectomy and supraglottoplasty. Unlike the trend in adults, multilevel surgery in children with sleep disordered breathing or OSA has not yet been integrated into routine clinical practice. LEVEL OF EVIDENCE: 2C Laryngoscope, 127:1235-1241, 2017.

Economic, Legal, and Social Hardships Associated with HIV Risk among Black Men who have Sex with Men in Six US Cities.

We assessed whether economic, legal, and social hardships were associated with human immunodeficiency virus (HIV) risk among a sample of Black men who have sex with men (MSM) and whether associations were moderated by city of residence. The study analyzed baseline and follow-up data from HIV Prevention Trials Network 061 (N = 1553). Binary logistic regression assessed associations between hardships and HIV risk indicators. Multivariate regressions were used to test if city of residence had a moderating effect for hardships and HIV risks. Adjusted analyses showed that Black MSM with recent job loss were more likely to engage in condomless insertive anal intercourse (adjusted odds ratios (AOR) = 1.37, 95% CI 1.01-1.87) and that those with recent financial crisis were more likely to have had two or more male sexual partners in the past 6 months (AOR = 1.65; 95% CI 1.18-2.29). Black MSM with recent convictions were more likely to have a sexually transmitted infection at 6 months (AOR = 3.97; 95% CI 1.58-9.94), while those who were unstably housed were more likely to have a sexually transmitted infection at 12 months (AOR = 1.71; 95%CI 1.02 = 2.86). There were no city of residence and hardship interaction effects on HIV risks. Hardships are important factors that influence HIV risk for Black MSM. Integrating strategies that address structural factors that influence HIV risk may enhance HIV prevention interventions implementation efforts.

Evaluation of a Community-Based Approach to Strengthen Retention in Early Childhood Home Visiting.

Home visiting (HV) is a strategy for delivering services designed to promote positive parenting and prevent exposure to toxic stress during a critical period of child development. Home visiting programs are voluntary and family engagement and retention in service can influence outcomes. Most participants receive less home visits and for a shorter time than prescribed by evidence-based models. The purpose of this study was to evaluate community-based enrichment of HV (CBE-HV), an approach that was developed and implemented to increase engagement and retention in HV. CBE-HV strategies included (1) community engagement, (2) ancillary supports for families in HV, and (3) enhancements to a HV program. A retrospective, quasi-experimental study was conducted to estimate the effect of CBE-HV on the retention of families in a HV program. Comparisons of study participants were made post-implementation of CBE-HV (n = 2191) and over time (n = 3786)-pre- versus post-CBE-HV implementation in the study communities. The CBE-HV effect was statistically significant and protective (hazards ratio [HR] 0.77, 95 % confidence interval [CI]: 0.67, 0.88), indicating that attrition from HV was 23 % less in the CBE-HV group relative to the post-implementation comparison group. In the temporal comparison of study communities, CBE-HV was also associated with a significantly lower risk of HV attrition (HR: 0.71, 95 % CI: 0.56, 0.89). The study demonstrated that CBE-HV is a promising approach to achieve stronger retention and engagement in HV. Further research is needed to identify the components of CBE-HV approaches that are most effective.