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Background Immunoglobulin A (IgA) is an important component of the early immune response to SARS-CoV-2. Prior serosurveys in high-risk groups employing IgG testing alone have provided discordant estimates. The potential added benefit of IgA in serosurveys has not been established. Methods Longitudinal serosurvey of first responders (police, emergency medical service providers, fire fighters, and other staff) employing 3 serologic tests (anti-spike IgA, anti-spike IgG, and anti-nucleocapsid IgG) correlated with surveys assessing occupational and nonoccupational risk, exposure to COVID-19, and illnesses consistent with COVID-19. Results Twelve percent of first responders in Colorado at baseline and 22% at follow-up were assessed as having SARS-CoV-2 infection. Five percent at baseline and 6% at follow-up were seropositive only for IgA. Among those IgA positive only at baseline, the majority (69%) had a positive antibody at follow-up; 45% of those infected at baseline and 33% at follow-up were asymptomatic. At all time points, the estimated cumulative incidence in our study was higher than that in the general population. Conclusions First responders are at high risk of infection with SARS-CoV-2. IgA testing identified a significant portion of cases missed by IgG testing and its use as part of serologic surveys may improve retrospective identification of asymptomatic infection.

In the United States, we are experiencing linked epidemics (a syndemic) of substance use disorders (SUDs) and infections associated with drug use, including unsafe injecting and unsafe sex in exchange for drugs or money. Current drug laws, together with risk-taking behavior among persons with SUDs, contribute to disproportionately high prevalences of these conditions in correctional settings. Detection and treatment of diseases with a high impact on public health are best addressed in the settings where such conditions are most prevalent (ie, jails and prisons for SUDs and chronic infections). The effectiveness, safety, cost of care. and public health impact of these conditions can be improved by means of broader screening and expanded access to specialty consultations through telemedicine/telehealth, along with broader use of long-acting medications for the treatment of human immunodeficiency virus and SUDs. Expanding telemedicine/telehealth, first for specialties which do not require advanced technology (eg, infectious diseases, addictions), can eventually lead to further advancements in correctional healthcare.

ObjectivesTo investigate the effectiveness of hydroxychloroquine and dexamethasone on coronavirus disease (COVID-19) mortality using patient data outside of randomized trials.DesignPhenotypes derived from electronic health records were analyzed using the stability-controlled quasi-experiment (SCQE) to provide a range of possible causal effects of hydroxy-chloroquine and dexamethasone on COVID-19 mortality.Setting and participantsData from 2,007 COVID-19 positive patients hospitalized at a large university hospital system over the course of 200 days and not enrolled in randomized trials were analyzed using SCQE. For hyrdoxychloroquine, we examine a high-use cohort (n=766, days 1 to 43) and a later, low-use cohort (n=548, days 44 to 82). For dexamethasone, we examine a low-use cohort (n=614, days 44 to 101) and high-use cohort (n=622, days 102 to 200).Outcome measure14-day mortality, with a secondary outcome of 28-day mortality.ResultsHydroxycholoroquine could only have been significantly (pConclusionsThe assumptions required for a beneficial effect of hydroxychloroquine on 14 day mortality are difficult to sustain, while the assumptions required for hydroxychloroquine to be harmful are difficult to reject with confidence. Dexamethasone, by contrast, was beneficial under a wide range of plausible assumptions, and was only harmful if a nearly impossible assumption is met. More broadly, the SCQE reveals what inferences can be credibly supported by evidence from non-randomized uses of experimental therapies, making it a useful tool when randomized trials have not yet produced clear evidence or to provide corroborative evidence from different populations.

Using a retrospective cohort analysis of inmates released from Dallas County Jail between January 2011 and November 2013, this study characterizes people living with HIV/AIDS (PLWHA) who are lost to care after release from jail. We used Kaplan-Meier analysis to estimate the risk of becoming lost to post-release HIV care and a Cox proportional hazards regression model to identify associated factors. The majority of individuals (78.2%) were men and 65.5% were black. Of the incarcerations that ended with release to the community, approximately 43% failed to link to community HIV care. Non-Hispanic Whites were more likely than Hispanics or Blacks to drop out of care after release. Individuals with histories of substance use or severe mental illness were more likely to become lost, while those under HIV care prior to incarceration and/or who had adhered to antiretroviral therapy (ART) were more likely to resume care upon release. Targeted efforts such as rapid linkage to care and re-entry residence programs could encourage formerly incarcerated individuals to re-engage in care.

The prevalence of HIV among people in correctional facilities remains much higher than that of the general population. Numerous studies have demonstrated the effectiveness and acceptability of HIV treatment for individuals incarcerated in US prisons and jails. However, the period following incarceration is characterized by significant disruptions in HIV care. These disruptions include failure to link in a timely manner (or at all) to community care post-release, as well as not being retained in care after linking. We used a retrospective, propensity-matched cohort design to compare retention in care between HIV-positive individuals recently released from prison (releasees) who linked to care in Ryan White HIV/AIDS Program (RWHAP) clinics and RWHAP patients without a recent incarceration history (community controls). We also performed analyses comparing viral load suppression of those retained in both groups. This study shows that even for those who do successfully link to care after prison, they are 24 to 29 percentage points less likely to be retained in care than those already in community care. However, we found that for those who did retain in care, there was no disparity in rates of viral suppression. These findings provide valuable insight regarding how best to address challenges associated with ensuring that HIV-positive individuals leaving prison successfully move through the HIV care continuum to become virally suppressed.

IMPORTANCE Preventive interventions are needed to protect residents and staff of skilled nursing and assisted living facilities from COVID-19 during outbreaks in their facilities. Bamlanivimab, a neutralizing monoclonal antibody against SARS-CoV-2, may confer rapid protection from SARS-CoV-2 infection and COVID-19. OBJECTIVE To determine the effect of bamlanivimab on the incidence of COVID-19 among residents and staff of skilled nursing and assisted living facilities. DESIGN, SETTING, AND PARTICIPANTS Randomized, double-blind, single-dose, phase 3 trial that enrolled residents and staff of 74 skilled nursing and assisted living facilities in the United States with at least 1 confirmed SARS-CoV-2 index case. A total of 1175 participants enrolled in the study from August 2 to November 20, 2020. Database lock was triggered on January 13, 2021, when all participants reached study day 57. INTERVENTIONS Participants were randomized to receive a single intravenous infusion of bamlanivimab, 4200mg (n = 588), or placebo (n = 587). MAIN OUTCOMES AND MEASURES The primary outcomewas incidence of COVID-19, defined as the detection of SARS-CoV-2 by reverse transcriptase���polymerase chain reaction and mild or worse disease severity within 21 days of detection, within 8 weeks of randomization. Key secondary outcomes included incidence of moderate or worse COVID-19 severity and incidence of SARS-CoV-2 infection. RESULTS The prevention population comprised a total of 966 participants (666 staff and 300 residents) who were negative at baseline for SARS-CoV-2 infection and serology (mean age, 53.0 [range, 18-104] years; 722 [74.7%] women). Bamlanivimab significantly reduced the incidence of COVID-19 in the prevention population compared with placebo (8.5%vs 15.2%; odds ratio, 0.43 [95%CI, 0.28-0.68]; P < .001; absolute risk difference, ���6.6 [95%CI, ���10.7 to ���2.6] percentage points). Five deaths attributed to COVID-19 were reported by day 57; all occurred in the placebo group. Among 1175 participants who received study product (safety population), the rate of participants with adverse events was 20.1% in the bamlanivimab group and 18.9% in the placebo group. The most common adverse events were urinary tract infection (reported by 12 participants [2%] who received bamlanivimab and 14 [2.4%] who received placebo) and hypertension (reported by 7 participants [1.2%] who received bamlanivimab and 10 [1.7%] who received placebo). CONCLUSIONS AND RELEVANCE Among residents and staff in skilled nursing and assisted living facilities, treatment during August-November 2020 with bamlanivimab monotherapy reduced the incidence of COVID-19 infection. Further research is needed to assess preventive efficacy with current patterns of viral strains with combination monoclonal antibody therapy.

This study sought to assess risk compensation following voluntary medical male circumcision of young school-going men. Risk compensation is defined as an inadvertent increase in sexual risk behaviors and a corresponding decrease in self-perceived risk for contracting HIV following the application of a risk reduction technology. This study documented the sexual practices of circumcised (n = 485) and uncircumcised (n = 496) young men in 42 secondary schools at three time points (baseline and 6 and 12 months) in a sub-district of KwaZulu-Natal, South Africa. Study participants were aged from 16 to 24 years old. At the end of the study period, there was no significant difference between the two cohorts concerning learners’ perceptions of being at risk of contracting HIV (interaction effect: b = −0.12, p = 0.40). There was also no significant difference in the number of sexual partners in the previous month (interaction effect: b = −0.23, p = 0.15). The proportion of learners who have never used a condom decreased significantly over time (time effect: b = −0.27, p = 0.01), and there was no difference between the circumcised and uncircumcised learners (interaction effect: b = −0.09, p = 0.91). Risk compensation, as evidenced in this study over a 1-year period, was not associated with undergoing voluntary medical male circumcision (VMMC) in our sample of young school-going men. However, it is of concern that at the end of this study, less than half of the sexually active sample in a high-HIV-prevalence community used condoms consistently in the previous month (39% for both study cohorts). The latter underscores the need to view VMMC as a potential entry point for planned HIV and sexuality education interventions targeting young men in this community.

Background Injection drug use is associated with serious infections. Due to challenges with medical management of addiction, relapses and additional infections are common. Persons who use drugs (PWUD) are more likely to leave against medical advice before completing treatment, which could result in treatment failure. Prolonged intravenous (IV) antimicrobial therapy in PWUD may be complicated by concern for IV catheter misuse, sometimes requiring prolonged hospitalization. Ideal alternatives would provide the following: (1) high success rate; (2) reduced rate of medical complications; (3) improved safety profiles; and (4) improved cost-effectiveness. Long-acting lipoglycopeptides present such opportunity for treatment of serious Gram-positive infections. Methods We performed a system-wide, retrospective analysis of adults admitted to University of Colorado Health from September 2015 to June 2018 and treated with dalbavancin or oritavancin based on clinical judgment of their treating physicians. Results Fifty-six patients met inclusion criteria (17 PWUD vs 39 non-PWUD). The PWUD group were younger, healthier by Charlson comorbidity index, more likely insured by Medicaid, and admitted for conditions requiring longer treatment. Ten patients were lost to follow-up. Of the patients with follow-up, clinical failure was met in 1 PWUD patient (6%) and 6 non-PWUD patients (15%) (P = .413). The median hospital length-of-stay reduction was 20 days (interquartile range [IQR], 10–30 days) in PWUD vs 11 days (IQR, 9–14 days) in non-PWUD; P = .133. Estimated median savings were $40 455.08 (IQR, $20 900.00–$62 700.00) in PWUD vs $19 555.08 (IQR, $15 375.08–$23 735.08) in non-PWUD; P = .065. Conclusions Long-acting lipoglycopeptides may be equally effective as standard-of-care, present a safety advantage, and secure earlier discharge and significant cost-savings.

Carbapenem-resistantEnterobacteriaceaeconferred by New Delhi metallo-b-lactamase (NDM-1) resistance mechanism are endemic in India and Southeast Asia. An understanding of risk factors for NDM-1 infections is necessary to guide prevention strategies. We performed a retrospective case-control study of patients admitted at Christian Medical College Hospital, Vellore, India between May 2010 and August 2014 withKlebsiella pneumoniaeblood stream infection (BSI). We compared patients with BSI caused by NDM-1 producing strains to two control groups: BSI with other multidrug resistant (MDR) strains and BSI with pan-susceptible strains. The study groups were assessed for risk factors for the outcomes: (1) infection with any MDR strain compared to pan-susceptible; and, (2) infection with NDM-1 strain as compared with other MDR and (3) Mortality. A total of 101 patients with BSI with NDM-1 producingKlebsiella pneumoniaewere matched to two groups of controls: 112 with non-NDM-1 MDR strains and 101 with pan-susceptible strains. Medical (OR 10.4) and neonatal (OR 0.7) ICU admission, central venous catheter placement (CVC, OR 7.4) predicted MDR BSI. Prior carbapenem use (OR 8.4) and CVC (OR 4.8) predicted acquisition of an NDM-1 strain. Significant predictors for mortality included ICU stay (OR 3.0), mechanical ventilation (OR 3.2), female gender (OR 2.2), diabetes (OR 0.4). CVC placement, prior carbapenem use and ICU admission were significantly associated with BSI with NDM-1 producing and other MDR strains.

BackgroundLong-acting lipoglycopeptides (laLGPs) are FDA approved only for acute bacterial skin and skin structure infections (ABSSSIs). However, these antibiotics show promise for off-label use, reductions in hospital length of stay (LOS) and healthcare cost savings.ObjectivesTo assess the effectiveness, safety, impact on LOS and estimated cost savings from laLGP treatment for Gram-positive infections.MethodsRetrospective cohort of adult patients who received at least one dose of laLGPs at the University of Colorado Health system. Descriptive statistics were utilized for analysis.ResultsOf 59 patients screened, 56 were included: mean age 47 years, 59% male and 30% injection drug users/polysubstance abusers (dalbavancin, 71%; oritavancin, 25%; both, 4%). Most common indications for laLGP: ABSSSIs (36%), osteomyelitis (27%) and endocarditis (9%). Most common isolated pathogens: MSSA and MRSA (25% and 19%, respectively), Enterococcus faecalis (11%) and CoNS (11%). Previous antibiotics were administered for a median of 13 days (IQR = 7.0–24.5 days) and laLGPs for a median of one dose (IQR = 1–2 doses). Ten (18%) patients were lost to follow-up. Clinical failure was found in 7/47 (15%) cases with adequate follow-up. Mild adverse effects occurred in six (11%) patients. Projected reduction in hospital LOS and health-system costs were 514 days (9.18 days/person average) and $963456.72 ($17204.58/person average), respectively.ConclusionsProspective trials are needed to validate the use of these antibiotics for Gram-positive infections in practice, with the hope that they will reduce hospital LOS and the need for daily antibiotic infusions to provide alternative options for patients not qualifying for outpatient parenteral antimicrobial therapy.

Transplant centers have varying policies for marijuana (MJ) use in donors, transplant candidates, and recipients. Rationales for these differences range from concerns for fungal complications, impaired adherence, and drug interactions. This paper reviews the current status of MJ policies and practices in transplant centers and results of a survey sent to the American Society of Transplantation (AST) membership by the Executive Committee of the AST Infectious Diseases Community of Practice.The purpose of the survey was to compare policies and concerns of MJ use to actual observed complications. Of the 3321 surveys sent, 225 members (8%) responded. Transplant centers varied in their approval processes, differing even in organ types within the same institutions. Furthermore, there was discordance among transplant centers in their perceived risks of marijuana use as opposed to complications actually observed. An increasing number of states continue to legalize medical and recreational MJ resulting in widespread availability. Further research is needed to assess the validity of concerns for complications of MJ use in potential donors and recipients. Ultimately, standardized guidelines should be established based on studies and evidence-based criteria to assist transplant programs in their policies around the use of cannabis in their donors and recipients.

The criminal justice system is a critical area of focus to improve HIV outcomes and reduce health disparities. We analyzed demographic, incarceration, socioeconomic, and clinical data for HIV-positive persons released to the community from the Dallas County Jail (1450 incarcerations, 1111 unique individuals) between January 2011 and November 2013. The study population was 68% black and 14% Hispanic; overall linkage to care within 90 days of release was 34%. In adjusted analyses, Hispanics were more likely to link than whites (aOR 2.33 [95% CI: 1.55–3.50]), and blacks were as likely to link as whites (aOR 1.14 [95% CI: 0.84–1.56]). The majority of HIV-positive jail releases did not re-engage in HIV care after release, though Hispanics were twice as likely as other groups to link to care. Further efforts are needed to improve the transition from jail to community HIV care with particular attention to issues of housing, mental illness, and substance use.

Incarcerated people remain a priority group in efforts to control and reverse the HIV epidemic. Following release, social instability and reengagement in key transmission risk behaviors increase the risk of secondary transmission of HIV. Targeted programs have been developed to facilitate reengagement in care on reentry. Evaluation of the impact of these initiatives requires a systematic, confidential, framework for assessment of linkage to care for persons released from corrections. By linking HIV viral load surveillance data to corrections release data, the time to the first laboratory monitoring service in the community as well as the virologic status can be assessed. Using this method, we linked release data for sentenced individuals released from Massachusetts state correctional facilities in 2012 to HIV surveillance data from the Massachusetts HIV/AIDS Surveillance Program (MHASP) for the years 2012-2013. We identified 41 individuals with HIV released in 2012. Ninety-one percent had identified virologic assessments post release, 41% within 30 days. Thirty-three percent did not have a viral load assessed for more than 90 days and 31% had detectable virus at the time of their initial assessment. Persons with longer incarcerations (> 180 days) were more likely to have suppressed viral load at the time of follow-up (p = 0.05). This work demonstrates the important value of HIV laboratory surveillance data and correctional release data as a tool to assess linkage to care following release from corrections. We encourage jurisdictions to explore utilizing similar methodology to evaluate the effectiveness of the linkage to HIV care after release from incarceration.

One in seven people living with HIV in the USA passes through a prison or jail each year, and almost all will return to the community. Discharge planning and transitional programs are critical but challenging elements in ensuring continuity of care, maintaining treatment outcomes achieved in prison, and preventing further viral transmission. This paper describes facilitators and challenges of in-prison care, transitional interventions, and access to and continuity of care in the community in Rhode Island and North Carolina based on qualitative data gathered as part of the mixed-methods Link Into Care Study of prisoners and releasees with HIV. We conducted 65 interviews with correctional and community-based providers and administrators and analyzed the transcripts using NVivo 10 to identify major themes. Facilitators of effective transitional systems in both states included the following: health providers affiliated with academic institutions or other entities independent of the corrections department; organizational philosophy emphasizing a patient-centered, personal, and holistic approach; strong leadership with effective "champions"; a team approach with coordination, collaboration and integration throughout the system, mutual respect and learning between corrections and health providers, staff dedicated to transitional services, and effective communication and information sharing among providers; comprehensive transitional activities and services including HIV, mental health and substance use services in prisons, timely and comprehensive discharge planning with specific linkages/appointments, supplies of medications on release, access to benefits and entitlements, case management and proactive follow-up on missed appointments; and releasees' commitment to transitional plans. These elements were generally present in both study states but their absence, which also sometimes occurred, represent ongoing challenges to success. The qualitative findings on the facilitators and challenges of the transitional systems were similar in the two states despite differences in context, demographics of target population, and system organization. Recommendations for improved transitional systems follow from the analysis of the facilitators and challenges.

Voluntary medical male circumcision (VMMC) is an integral part of South Africa’s HIV prevention programme. School-going males, in particular, are considered a cost-effective target population. However, ambitious policy targets have not been achieved due to the plateau in demand for VMMC. This study documents the factors influencing demand for VMMC amongst school-going males. Data were collected from 750 learners (251 circumcised and 499 uncircumcised) from 42 secondary schools in KwaZulu-Natal, South Africa. There was a positive association between the perceived benefit of VMMC and the likelihood of undergoing circumcision (AOR: 1.41, p = 0.01). There was a negative association between self-efficacy to use condoms and likelihood of undergoing VMMC (AOR: 0.75, p < 0.01). Learners who perceived VMMC as having a number of health benefits, including reducting of the chances of contracting HIV and sexually transmitted infections (STIs), increasing penile hygiene and the belief that VMMC allows them to use condoms less frequently, were more likely to undergo VMMC. Of concern, learners who were confident in their ability to access condoms and t use a condom with their partner were less likely to undergo VMMC. Keywords: adolescent friendly health services, circumcision for HIV prevention, demand for circumcision, HIV/AIDS, HIV prevention, South Africa

Objectives In this study, Increasing Viral Testing in the Emergency Department (InVITED), the authors investigated if a brief intervention about human immunodeficiency virus (HIV) and hepatitis C virus (HCV) risk-taking behaviors and drug use and misuse in addition to a self-administered risk assessment, compared to a self-administered risk assessment alone, increased uptake of combined screening for HIV and HCV, self-perception of HIV/HCV risk, and impacted beliefs and opinions on HIV/HCV screening. Methods InVITED was a randomized, controlled trial conducted at two urban emergency departments (EDs) from February 2011 to March 2012. ED patients who self-reported drug use within the past 3 months were invited to enroll. Drug misuse severity and need for a brief or more intensive intervention was assessed using the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST). Participants were randomly assigned to one of two study arms: a self-administered HIV/HCV risk assessment alone (control arm) or the assessment plus a brief intervention about their drug misuse and screening for HIV/HCV (intervention arm). Beliefs on the value of combined HIV/HCV screening, self-perception of HIV/HCV risk, and opinions on HIV/HCV screening in the ED were measured in both study arms before the HIV/HCV risk assessment (pre), after the assessment in the control arm, and after the brief intervention in the intervention arm (post). Participants in both study arms were offered free combined rapid HIV/HCV screening. Uptake of screening was compared by study arm. Multivariable logistic regression models were used to evaluate factors related to uptake of screening. Results Of the 395 participants in the study, the median age was 28 years (interquartile range [IQR] = 23 to 38 years), 44.8% were female, 82.3% had ever been tested for HIV, and 67.3% had ever been tested for HCV. Uptake of combined rapid HIV/HCV screening was nearly identical by study arm (64.5% vs. 65.2%; Δ = –0.7%; 95% confidence interval [CI] = –10.1% to 8.7%). Of the 256 screened, none had reactive HIV antibody tests, but seven (2.7%) had reactive HCV antibody tests. Multivariable logistic regression analysis results indicated that uptake of screening was not related to study arm assignment, total ASSIST drug scores, need for an intervention for drug misuse, or HIV/HCV sexual risk assessment scores. However, uptake of screening was greater among participants who indicated placing a higher value on combined rapid HIV/HCV screening for themselves and all ED patients and those with higher levels of perceived HIV/HCV risk. Uptake of combined rapid HIV/HCV screening was not related to changes in beliefs regarding the value of combined HIV/HCV screening or self-perceived HIV/HCV risk (post– vs. pre–risk assessment with or without a brief intervention). Opinions regarding the ED as a venue for combined rapid HIV/HCV screening were not related to uptake of screening. Conclusions Uptake of combined rapid HIV/HCV screening is high and considered valuable among drug using and misusing ED patients with little concern about the ED as a screening venue. The brief intervention investigated in this study does not appear to change beliefs regarding screening, self-perceived risk, or uptake of screening for HIV/HCV in this population. Initial beliefs regarding the value of screening and self-perceived risk for these infections predict uptake of screening. Resumen Objetivos El estudio Increasing Viral Testing in the Emergency Department (InVITED) investiga si una intervencion breve sobre los comportamientos de riesgo en relacion con el virus de inmunodeficiencia humana (VIH) y la hepatitis C (VHC), consumo y abuso de drogas, junto con una evaluacion autoadministrada del riesgo, en comparacion con solo la evaluacion autoadministrada del riesgo, incrementaba la aceptacion de despistaje combinado de VIH y VHC, el riesgo autopercibido de VIH/VHC, y las creencias y opiniones del despistaje de VIH/VHC. Metodologia InVITED fue un ensayo clinico controlado y aleatorizado llevado a cabo en dos SU urbanos de febrero de 2011 a marzo de 2012. Se invito a participar a los pacientes del SU que autorefirieron consumo de drogas en los tres ultimos meses. La gravedad del abuso de drogas y la necesidad de una intervencion breve o mas intensa se valoro usando el Alcohol, Smoking and Substance Involvement Screening Test (ASSIST). Los pacientes fueron asignados aleatoriamente a uno de los dos brazos del estudio: solamente evaluacion autoadministrada del riesgo de VIH/VHC (grupo control) o la evaluacion mas una intervencion breve sobre sus abusos de drogas y el despistaje de VIH/VHC (grupo de intervencion). Se midieron las creencias acerca del valor del despistaje combinado VIH/VHC, la autopercepcion del riesgo de VIH/VHC, y las opiniones acerca del despistaje de VIH/VHC en el SU en ambos brazos del estudio antes de la evaluacion del riesgo de VIH/VHC (pre), despues de la evaluacion en el grupo control, y despues de la intervencion breve (post). Se ofrecio gratuitamente un test de despistaje rapido VIH/VHC a los participantes de ambos brazos del estudio. La aceptacion del despistaje se comparo segun el brazo del estudio. Se usaron modelos de regresion logistica multivariable para evaluar los factores relacionados con la aceptacion del despistaje. Resultados De los 395 participantes del estudio, la mediana de edad fue de 28 anos (RIC de 23 a 38), un 44,8% fueron mujeres, un 82,3% nunca habia recibido un test de VIH, y un 67,3% nunca de VHC. La aceptacion del despistaje rapido combinado de VIH/VHC fue practicamente igual en ambos brazos del estudio (64,5% contra 65,2%; Δ = -0,7%; IC 95% = -10,1% a 8,7%). De los 256 a los que se les realizo el despistaje, ninguno tuvo un test de anticuerpos de VIH positivo, pero siete (2,7%) presentaron un test de anticuerpos de VHC positivo. Los resultados del analisis de regresion logistica multivariable indicaron que la aceptacion del despistaje no se relaciono con el brazo de asignacion del estudio, el total de las puntuaciones del test ASSIST, la necesidad de una intervencion sobre el abuso de drogas, o las puntuaciones de evaluacion del riesgo sexual de VIH/VHC. Sin embargo, la aceptacion del despistaje fue mayor entre los participantes que indicaron otorgar un mayor valor al despistaje rapido combinado de VIH/VHC para si mismos y para todos los pacientes del SU, y aquellos con mayores niveles de riesgo percibido de VIH/VHC. La aceptacion del despistaje rapido combinado de VIH/VHC no se relaciono con cambios en las creencias sobre el valor del despistaje combinado VIH/VHC o la autopercepcion del riesgo de VIH/VHC (valoracion del riesgo pre, con o sin intervencion breve, frente a post). Las opiniones acerca del SU como un lugar para el despistaje rapido combinado de VIH/VHC no se relacionaron con la aceptacion del despistaje. Conclusiones La aceptacion del despistaje rapido combinado de VIH/VHC es elevada y se considero valiosa entre los pacientes del SU con consumo o abuso de drogas sin mucha preocupacion sobre el SU como lugar de despistaje. La intervencion breve investigada en este estudio no parece cambiar las creencias acerca del despistaje, el riesgo autopercibido, o la aceptacion del despistaje de VIH/VHC en esta poblacion. Las creencias iniciales respecto al valor del despistaje y al riesgo autopercibido para estas infecciones predijeron la aceptacion del despistaje.

Voluntary medical male circumcision is an integral part of the South African government’s response to the HIV and AIDS epidemic. Following circumcision, it is recommended that patients abstain from sexual activity for six weeks, as sex may increase the risk of female-to-male HIV transmission and prolong the healing period. This paper investigates the resumption of sexual activity during the healing period among a cohort of school-going males in the KwaZulu-Natal province of South Africa. The analysis for this paper compares two groups of sexually active school-going males: the first group reported having sex during the healing period (n = 40) and the second group (n = 98) reported no sex during the healing period (mean age: 17.7, SD: 1.7).The results show that 29% (n = 40) of young males (mean age: 17.9, SD: 1.8) who were previously sexually active, resumed sexual activity during the healing period, had on average two partners and used condoms inconsistently. In addition, those males that engage in sexual activity during the healing period were less inclined to practice safe sex in the future (AOR = 0.055, p = 0.002) than the group of males who reported no sex during the healing period. These findings suggest that a significant proportion of young males may currently and in the future, subject themselves to high levels of risk for contracting HIV post circumcision. Education, as part of a VMMC campaign, must emphasize the high risk of HIV transmission for both the males their partners during the healing period.

Populations in corrections continue to have high prevalence of HIV. Expanded testing and treatment programs allow persons to be identified and stabilized on treatment while incarcerated. However, these gains and frequently lost on reentry. Systemic frameworks are needed to monitor linkage to care to guide programs supporting linkage to care. To assess the adequacy of linkage to care on reentry, incarceration data from the National Corrections Reporting Program and data from the Ryan White Services Report from 2010 to 2012 were linked using an encrypted client identification (eUCI). Time from release to the first visit and presence of detectable HIV RNA at linkage were assessed. Multivariate survival analyses were performed to identify associations between patient characteristics and time to linkage. Among those linking, only 43% in Rhode Island and 49% in North Carolina linked within 90 days, and 33% in both states had detectable viremia at the first visit. Those not previously in care and with shorter incarceration experiences longer linkage times. Persons identified as black, had median times greater than 1 year. Using existing datasets, significant gaps in linkage to care for persons with HIV on release from corrections were demonstrated in Rhode Island and North Carolina. Systemically implementing this monitoring to evaluate changes over time would provide important information to support interventions to improve linkage in high-risk populations. Using national datasets for both corrections and clinical data, this framework equally could be used to evaluate experiences of persons with HIV linking to care on release from corrections facilities nationwide.

Background: HIV-infected refugees resettled in the United States face many challenges. Longitudinal data regarding HIV-specific outcomes in this population are limited. Methods: We reviewed charts of 51 HIV-infected sub-Saharan African refugees matched to 102 nonrefugees. Outcomes analyzed included CD4 counts, viral loads (VLs), antiretroviral treatment (ART) use, appointment adherence, opportunistic infections, and resistance mutations. Results: The ART initiation was similar. Appointment adherence was similar in year 1, but refugees were significantly less adherent beyond year 3. Refugees and nonrefugees spent similar amounts of time in care suppressed (83% vs 80%, P = .93). Refugees had higher odds of viremia following undetectable VL (OR 2.3, P < .05). Discussion: Initially, sub-Saharan African HIV-infected refugees have comparable appointment adherence, ART use, and VL suppression to nonrefugees. Overtime refugees were less adherent to appointments and more likely to have postsuppression viremia. The support services provided to refugees early in care may be important for retention in care and treatment success.

Improving testing and uptake to care among highly impacted populations is a critical element of Seek, Test, Treat and Retain strategies for reducing HIV incidence in the community. HIV disproportionately impacts prisoners. Though, incarceration provides an opportunity to diagnose and initiate therapy, treatment is frequently disrupted after release. Though model programs exist to support linkage to care on release, there is a lack of scalable metrics with which to assess adequacy of linkage to care after release. The linking data from Ryan White program Client Level Data (CLD) files reported to HRSA with corrections release data offers an attractive means of generating these metrics. Identified only by use of a confidential encrypted Unique Client Identifier (eUCI) these CLD files allow collection of key clinical indicators across the system of Ryan White funded providers. Using eUCIs generated from corrections release data sets as a linkage tool, the time to the first service at community providers along with key clinical indicators of patient status at entry into care can be determined as measures of linkage adequacy. Using this strategy, high and low performing sites can be identified and best practices can be identified to reproduce these successes in other settings.

In the USA, the burden of hepatitis B disproportionately affects high-risk adults who alone account for more than 75% of newly reported hepatitis B virus infections each year. Despite the localization of new infections in identifiable high-risk groups, vaccination rates in this subgroup, with the exception of health care workers, remain consistently low. The purpose of this study was to characterize those at risk for hepatitis B transmission and quantify the association between missed opportunities and hepatitis B vaccination. Data from the 2007 Behavioral Risk Factor Surveillance Survey (BRFSS) of adults aged 18 years and older who were at high risk for hepatitis B infection (n = 15,432) were analyzed. Multivariate regression analysis was conducted to determine factors independently associated with vaccination. In a nationally representative sample, 51.4% of high-risk adults remained unvaccinated against hepatitis B and more than 50% had a missed opportunity for vaccination. High-risk adults who were vaccinated against pneumonia and influenza had a higher odds ratio of being vaccinated against hepatitis B than those not vaccinated against pneumonia and influenza (OR 2.27 and 1.67, respectively). Also, high-risk adults tested for human immunodeficiency virus (HIV) at a counseling and testing site or a drug treatment facility had a higher OR of being vaccinated than those who had not been tested for HIV (OR 1.78 and 1.73, respectively). The opposite relationship was true among individuals tested for HIV at a correctional facility (OR 0.60). The findings of this study underscore the inadequacy of vaccination coverage in high-risk adults and highlight advantageous opportunities to bridge gaps in vaccination coverage.

Background The use of antiretroviral (ARV) dual therapy for treatment of HIV is increasing; raltegravir with boosted darunavir (bDRV) is recommended in certain clinical situations in DHHS guidelines. Dolutegravir (DTG) with bDRV has not been widely studied. We sought to determine the effectiveness of DTG/bDRV in treatment experienced patients. Methods This retrospective cohort study evaluated viral suppression in patients prescribed DTG/bDRV dual therapy within a large urban health system. Data collected included demographics, cumulative ARV exposure, reasons for use, regimen start/stop dates, and viral suppression (HIV-RNA ≤200). Follow-up was defined as the number of days from start of regimen until last HIV-RNA determination on the study regimen. Results From January 1, 2013 to December 31, 2017, 60 patients received DTG/bDRV dual therapy: 15% were female, median age was 56, 83% were ≥3 class ARV-experienced, and median time since starting ARVs was 20 years. Median follow-up on DTG/bDRV was 444 days (IQR 273–808). Viral suppression was achieved by 59 of 60 (98%) patients at some point on DTG/bDRV. When stratified by baseline viral suppression, 46 of 46 (100%) who had baseline viral suppression maintained viral suppression in comparison to 11 of 14 (79%) without baseline viral suppression (table). The most common reasons for DTG/bDRV were simplification in setting of prior resistance (47%), toxicity reduction (39%), and virologic failure (15%). At study end, 53 of 60 (88%) were still on DTG/bDRV and the most common reason for stopping was drug interactions. Conclusion In a highly treatment-experienced cohort of patients, DTG/bDRV dual therapy demonstrated sustained rates of viral suppression, even in those who were failing therapy prior to initiating the regimen. Further study of this potent, simple, high-barrier dual class regimen is warranted. Disclosures S. Rowan, Gilead Sciences: Investigator, Research grant. S. C. Johnson, Viiv Healthcare: Scientific Advisor, Consulting fee.

CONTEXT Research has demonstrated the potential adverse impact of pharmaceutical company marketing techniques on doctor knowledge and prescribing practices. Lack of experience may make resident doctors particularly vulnerable to pharmaceutical industry influence. Curricula addressing resident-pharmaceutical industry relations have been reported, but there is no consensus regarding the best approach to take. OBJECTIVE This study aimed to review published curricula that address resident-pharmaceutical industry relations and to assess them for content, validity and outcomes measures. METHODS Curricula were identified via searches of electronic databases and bibliographies of collected articles. Inclusion criteria required articles to describe an educational curriculum, applied in graduate medical education, on relations between doctors and the pharmaceutical industry. RESULTS The search identified 9 curricula. Most addressed detailing of residents by pharmaceutical representatives. Two articles described curriculum development. Eight articles included an evaluation component; only 1 included a control group for comparison. Modest improvements were noted in resident confidence, knowledge of guidelines, belief in the potential influence of marketing on behaviour, and self-reported acceptance of gifts. Only 2 evaluations used a validated outcome instrument, and no studies included longterm follow-up. CONCLUSIONS A limited number of curricula have addressed resident-pharmaceutical industry interactions. Inconsistency in content, application and evaluation methodology prevents any meaningful synthesis of data. Resident attitudes and behaviours may be affected, but the outcome measures used lacked sufficient validity to assess improvements in knowledge and analytic skills. A clearer delineation of the curriculum development process and the use of standardised outcome measures would facilitate the reproduction of positive results at other institutions.

Unhealthy alcohol use is common among HIV-infected patients and contributes to co-morbidities, cognitive decline, unprotected sex, and poor medication adherence. Studies consistently show missed opportunities to address unhealthy alcohol use as part of care. Although treatment of other drug use has been integrated into HIV care in some settings, more information is needed regarding provider attitudes regarding the need for integration of alcohol treatment and HIV care.We surveyed 119 HIV and 159 addiction providers regarding the following domains: existing knowledge, desire for new knowledge (with subdomains relative advantage, compatibility, and complexity of integrating knowledge), and individual and program development needs. Scale scores for each domain were correlated with demographics to identify factors associated with training need.Both HIV and addiction providers reported agreement with statements of existing knowledge and the need for additional skills. The priority attributed to training, however, was low for both groups. Knowledge and perceived prevalence of HIV and unhealthy alcohol use increased with years of experience. Perceived prevalence correlated with compatibility but not the relative advantage of training.Though addressing alcohol use and HIV was acknowledged to be important, the priority of this was low, particularly early career providers. These providers may be important targets for training focusing on motivating coordination of care and skills related to assessment and counseling.

Objective: To investigate the relation between biochemical markers of bone, cartilage, and synovial remodelling and the structural progression of knee osteoarthritis. Methods: 62 patients of both sexes with knee osteoarthritis were followed prospectively for one year. From magnetic resonance imaging (MRI), done at baseline and after one year, the volume and thickness of cartilage of the femur, the medial tibia, and the lateral tibia were assessed. A whole organ magnetic resonance imaging score (WORMS) of the knee was calculated for each patient at baseline and at the one year visits. This score consists in a validated, semiquantitative scoring system for whole organ assessment of the knee in osteoarthritis using MRI. Biochemical markers (serum hyaluronic acid, osteocalcin, cartilage glycoprotein 39 (YKL-40), cartilage oligomeric matrix protein (COMP), and C-telopeptide of type I collagen (CTX-I), and urine C-telopeptide of type II collagen (CTX-II)) were measured at baseline and after three months. Results: Baseline markers were not correlated with one year changes observed in cartilage volume and thickness. However, an increase in CTX-II after three months was significantly correlated with a one year decrease in mean thickness of medial tibial and lateral tibial cartilage. Patients in the highest quartile of three month changes in CTX-II experienced a mean loss of 0.07 (0.08) mm of their medial thickness, compared with a mean increase of 0.05 (0.19) mm for patients in the lowest quartile (p = 0.04) Multiple regression analysis showed that high baseline levels of hyaluronic acid are predictive of a worsening in WORMS (p = 0.004). Conclusions: These results suggest that a single measurement of serum hyaluronic acid or short term changes in urine CTX-II could identify patients at greatest risk of progression of osteoarthritis.

Hypertension is strongly related to cardiovascular disease and all-cause mortality. Exercise reduces blood pressure but the response varies between individuals. The mechanisms by which physical activity energy expenditure (PAEE) modifies blood pressure are not fully defined but include modulation of sympathetic tone. Novel polymorphisms in the G-protein coupled receptor (GPR10) have been linked with high blood pressure. GPR10 may mediate the relationship between PAEE and blood pressure via central nervous mechanisms. We examined whether two GPR10 polymorphisms ( G -62A and C914T) modify the association between PAEE and blood pressure in the MRC Ely study (N=687). When stratified by the C914T genotype, there were between-group differences for body mass index (BMI) ( P =0.05), diastolic blood pressure (DBP) ( P =0.006), and systolic blood pressure (SBP) ( P =0.005). No differences were found between G -62A genotypes. The previously reported inverse relationship between PAEE and blood pressure was not observed in minor allele carriers for either polymorphism (A62 carriers: DBP β-1.11, P =0.52; SBP β-1.66, P =0.52. T914 carriers: SBP β=3.27; P =0.60) but was in common allele homozygotes (G62G: DBP β-6.18 P =0.00001; SBP β-8.54 P =0.0001. C914C: SBP β-7.07; P =0.00001). This corresponded to a significant interaction between PAEE and GPR10 polymorphisms on DBP ( G -62A: P =0.006) and SBP ( G -62A: P =0.008. C914T: P =0.068). Significant interactions were observed between haplotype (derived from G -62A and C914T), PAEE, and blood pressure (DBP: P =0.08; SBP: P =0.023). The effect of physical activity on blood pressure is highly variable at population level. Knowledge of GPR10 genotype may define those who are least likely to benefit from physical activity. These findings may have relevance in the targeted treatment of hypertensive disease.

Catcher bearings (CBs) provide backup protection for rotating machines with active magnetic bearings (AMBs). The CBs are required in the event of an AMB failure or high transient loads. Numerical simulations of a rotor drop on CBs in flywheel energy storage system are conducted with a detailed CB model which includes a Hertzian load–deflection relationship between mechanical contacts, speed-and-preload-dependent bearing stiffness due to centrifugal force, and a Palmgren's drag friction torque. The transient simulation results show the rotor shaft response variations with the design parameters: shaft/bearing friction coefficients, axial preload, support damping of damper liner, and side loads from magnetic bearings. The results reveal that friction coefficients, support damping, and side loads are critical parameters to satisfy CB design objectives and prevent backward (super) whirl.

This paper describes the management of a 24-month-old boy who presented with self-inflicted trauma to his lower lip and tongue, and teeth grinding, 21 days after developing meningococcal septicaemia. A decision to observe and prescribe palliative therapy was made. Extraction of the lower right deciduous canine, which had become non-vital, possibly due to bruxism, was carried out.

Background The Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004 trial demonstrated a 39% reduction in HIV infection, with a 54% HIV reduction in women who used tenofovir gel consistently. A confirmatory trial is expected to report results in early 2015. In the interim, we have a unique window of opportunity to prepare for and devise effective strategies for the future policy and programmatic scale-up of tenofovir gel provision. One approach is to integrate tenofovir gel provision into family planning (FP) services. The CAPRISA 008 implementation trial provides an opportunity to provide post-trial access to tenofovir gel while generating empiric evidence to assess whether integrating tenofovir gel provision into routine FP services can achieve similar levels of adherence as the CAPRISA 004 trial. Methods/design This is a two-arm, open-label, randomized controlled non-inferiority trial. A maximum of 700 sexually active, HIV-uninfected women aged 18 years and older who previously participated in an antiretroviral prevention study will be enrolled from an urban and rural site in KwaZulu-Natal, South Africa. The anticipated study duration is 30 months, with active accrual requiring approximately 12 months (following which an open cohort will be maintained) and follow-up continuing for approximately 18 months. At each of the two sites, eligible participants will be randomly assigned to receive tenofovir gel through either FP services (intervention arm) or through the CAPRISA research clinics (control arm). As part of the study intervention, a quality improvement approach will be used to assist the FP services to expand their current services to include tenofovir gel provision. Discussion This protocol aims to address an important implementation question on whether FP services are able to effectively incorporate tenofovir gel provision for this at-risk group of women in South Africa. Provision of tenofovir gel to the women from the CAPRISA 004 trial meets the ethical obligation for post-trial access, and helps identify a potential avenue for future scale-up of microbicides within the public health system of South Africa. Trial registration This trial was registered with the South Africa Department of Health (reference: DOH-27-0812-4129) and ClinicalTrials.gov (reference: NCT01691768) on 05 July 2012.

Incarceration provides an opportunity to test for HIV, provide treatment such as highly active anti-retroviral therapy, as well as link infected persons to comprehensive HIV care upon their release. A key factor in assessing the success of a program that links released individuals to care is the time from release to receiving care in the community (linkage time). To estimate the linkage time, records from correction systems are linked to Ryan White Clinic data using encrypted Unique Client Identifier (eUCI). Most of the records that were linked using eUCI belong to the same individual; however, in some cases, it may link records incorrectly, or not identify records that should have been linked. We propose a Bayesian procedure that relies on the relationships between variables that appear in either of the data sources, as well as variables that exists in both to identify correctly linked records among all linked records. The procedure generates K datasets in which each pair of linked records is identified as a true link or a false link. The K datasets are analyzed independently, and the results are combined using Rubin's multiple imputation rules. A small validation dataset is used to examine different statistical models and to inform the prior distributions of the parameters. In comparison with previously proposed methods, the proposed method utilizes all of the available data and is both flexible and computationally efficient. In addition, this approach can be applied in other file linking applications.

Purpose – The purpose of this paper is to consider the potential benefits and challenges of applying a strategy of “seek, test, treat and retain” (STTR) to hepatitis C virus (HCV) in the US criminal justice system. Design/methodology/approach – The authors draw on the published literature to illustrate how each component of STTR could be applied to HCV in the US criminal justice system, and describe challenges to the implementation of this strategy. Findings – The burden of morbidity and mortality associated with chronic HCV infection in the USA is increasing and without significantly increased treatment uptake, will likely continue to do so for several decades. The authors argue that the US criminal justice system is an ideal focus for HCV case finding and treatment due to a high prevalence of infection and large volume of individuals in contact with this system. STTR would identify large numbers of HCV infections, leading to opportunities for secondary prevention and primary care. Important challenges to the implementation of STTR include treatment costs and training of prison medical providers. Originality/value – This paper highlights opportunities to address HCV in the US criminal justice system.

Epidemiological modelling has concluded that if voluntary medical male circumcision (VMMC) is scaled up in high HIV prevalence settings it would lead to a significant reduction in HIV incidence rates. Following the adoption of this evidence by the WHO, South Africa has embarked on an ambitious VMMC programme. However, South Africa still falls short of meeting VMMC targets, particularly in KwaZulu-Natal, the epicentre of the HIV/AIDS epidemic. A qualitative study was conducted in a high HIV prevalence district in KwaZulu-Natal to identify barriers and facilitators to the uptake of VMMC amongst adolescent boys. Focus group discussions with both circumcised and uncircumcised boys were conducted in 2012 and 2013. Analysis of the data was done using the framework approach and was guided by the Social Cognitive Theory focussing on both individual and interpersonal factors influencing VMMC uptake. Individual cognitive factors facilitating uptake included the belief that VMMC reduced the risk of HIV infection, led to better hygiene and improvement in sexual desirability and performance. Cognitive barriers related to the fear of HIV testing (and the subsequent result and stigmas), which preceded VMMC. Further barriers related to the pain associated with the procedure and adverse events. The need to abstain from sex during the six-week healing period was a further prohibiting factor for boys. Timing was crucial, as boys were reluctant to get circumcised when involved in sporting activities and during exam periods. Targeting adolescents for VMMC is successful when coupled with the correct messaging. Service providers need to take heed that demand creation activities need to focus on the benefits of VMMC for HIV risk reduction, as well as other non-HIV benefits. Timing of VMMC interventions needs to be considered when targeting school-going boys.Keywords: adolescents, demand creation, HIV, VMMC, South AfricaAfrican Journal of AIDS Research 2014, 13(2): 179–187

Background: Epidemiological data from South Africa demonstrate that risk of human immunodeficiency virus (HIV) infection in males increases dramatically after adolescence. Targeting adolescent HIV-negative males may be an efficient and cost-effective means of maximising the established HIV prevention benefits of voluntary medical male circumcision (VMMC) in high HIV prevalence–, low circumcision practice–settings. This study assessed the feasibility of recruiting male high school students for VMMC in such a setting in rural KwaZulu-Natal. Methods and Findings: Following community and key stakeholder consultations on the acceptability of VMMC recruitment through schools, information and awareness raising sessions were held in 42 high schools in Vulindlela. A three-phase VMMC demand-creation strategy was implemented in partnership with a local non-governmental organization, ZimnadiZonke, that involved: (i) community consultation and engagement; (ii) in-school VMMC awareness sessions and centralized HIV counselling and testing (HCT) service access; and (iii) peer recruitment and decentralized HCT service access. Transport was provided for volunteers to the Centre for the AIDS Programme of Research in South Africa (CAPRISA) clinic where the forceps-guided VMMC procedure was performed on consenting HIV-negative males. HIV infected volunteers were referred to further care either at the CAPRISA clinic or at public sector clinics. Between March 2011 and February 2013, a total of 5165 circumcisions were performed, the majority (71%) in males aged between 15 and 19 years. Demand-creation strategies were associated with an over five-fold increase in VMMC uptake from an average of 58 procedures/month in initial community engagement phases, to an average of 308 procedures/month on initiation of the peer recruitment– decentralized service phase. Post-operative adverse events were rare (1.2%), mostly minor and self-resolving. Conclusions: Optimizing a high volume, adolescent-targeted VMMC program was feasible, acceptable and safe in this setting. Adaptive demand-creation strategies are required to sustain high uptake.

Early diagnosis of HIV and effective antiretroviral treatment are key elements in efforts to reduce the morbidity and mortality associated with HIV. Incarcerated populations are disproportionately affected by HIV, with the disease’s prevalence among inmates estimated to be three to five times higher than among the general population. Correctional institutions offer important opportunities to test for HIV and link infected people to postrelease treatment services. To examine HIV testing and policies that help HIV-positive people obtain treatment in the community after release, we administered a survey to the medical directors of the fifty state prison systems and of forty of the largest jails in the United States. We found that 19 percent of prison systems and 35 percent of jails provide opt-out HIV testing, which is recommended by the Centers for Disease Control and Prevention (CDC). Additionally, fewer than 20 percent of prisons and jails conform to the CDC’s recommendations regarding discharge planning services for inmates transitioning to the community: making an appointment with a community health care provider, assisting with enrollment in an entitlement program, and providing a copy of the medical record and a supply of HIV medications. These findings suggest that opportunities for HIV diagnosis and linking HIV-positive inmates to community care after release are being missed in the majority of prison systems and jails.

SummaryThe effects of argatroban, a direct thrombin inhibitor, on the International Normalized Ratio (INR), activated partial thromboplastin time (aPTT) and functional factor X during warfarin co-administration were established to provide means to interpret INRs during argatroban/warfarin co-therapy. Twenty-four subjects receiving warfarin (7.5 mg, day 1; 3-6 mg/day, days 2-10) and argatroban (1-4 μg/kg/min over 5 h, days 1-11) were assessed daily for these coagulation parameters prior to argatroban infusion (warfarin “monotherapy”) and at its conclusion (“co-therapy”). Argatroban increased aPTTs dose-dependently. Co-therapy INR increased linearly with monotherapy INR, with slope sensitive to argatroban dose and thromboplastin used. Prediction errors for monotherapy INRs were ≤± 0.4 for argatroban 1-2 μg/kg/min but ≥± 1.0 for higher doses. Despite co-therapy INRs >7, no major bleeding occurred. Factor X remained ≥37% of normal. Therefore, the predictable effect of argatroban (≤ 2 mg/kg/min only) on INRs during warfarin co-therapy allows for reliable prediction of the level of oral anticoagulation.

Jet engines may experience severe vibration due to the sudden imbalance caused by blade failure. The current research investigates employment of piezoelectric actuators to suppress this using active vibration control. This requires identification of the source of the vibrations via an expert system, determination of the required phase angles and amplitudes for the correction forces, and application of the desired control signals to the piezoelectric actuators. Correction forces may exceed the physical limitations of the actuators; hence results of “constrained force” quadratic programming, least squares and multi-point correction algorithms will be compared. It is demonstrated that simply scaling down the least squares predicted correction forces to satisfy the actuator saturation constraints does not necessarily yield optimal reductions in vibration. In this paper test results are shown for sudden imbalance, and the computational time requirements and balancing effectiveness for the various approaches are compared.

Electromechanical modeling of a hybrid piezohydraulic actuator system for active vibration control was developed. The transfer function of piezoelectric actuator was derived from the electromechanical potential energy law. This transfer function represents the dynamic relationship between input electric voltage and piezoelectric actuator displacement. The hydraulic actuator was characterized by impedance matching in which its transfer functions were experimentally determined. The transfer functions were transformed into a state-space representation, which is easily assembled into an active vibration control (AVC) closed-loop simulation. Good correlation of simulation and test was achieved for the hybrid system. A closed-loop dynamic simulation for imbalance response with/without AVC of a spinning rotor test rig at NASA Lewis was performed and showed excellent agreement with test results. The simulation couples the piezoelectric, hydraulic, and structural (rotor) components.

Background. Adolescents in South Africa (SA) have a huge unmet need for sexual and reproductive health (SRH) services. Integrating such services into schools may overcome many of the current barriers to access. Objectives. We describe an SRH service model developed for high-school students and its implementation in 14 high schools in rural SA. Methods. Following consultation with community and other key stakeholders about the demand for and acceptability of adolescent-targeted SRH services, a three-tier school-based model was developed that included: ( i ) in-school group SRH information and awareness sessions; ( ii ) in-school individual SRH counselling and customised HIV counselling and testing (CCT); and ( iii ) referrals to in-school fixed, in-school mobile or public sector primary SRH clinics. Results. From October 2011 to June 2012, 70 consultative meetings were held. There was overwhelming support for the pilot founded on concerns about the high HIV prevalence and teenage pregnancy rates among adolescents in the community. SRH information was provided to 8 867 high-school students, 4 171 (47.0%) of whom accessed on-site CCT services for HIV. The gender-specific prevalence of HIV in these students was 3.3% (64/1 962) and 1.1% (24/2 209) for females and males, respectively. Two hundred and thirty-nine students (5.7%) were referred for clinical services at in-school fixed, in-school mobile or public sector primary SRH clinics. Conclusions. The SRH service provision pilot was acceptable in the community and seems feasible for scale-up. Further work is required to understand inter-school variability in uptake, identify additional service needs of students, and characterise SRH demand dynamics.

Reimbursement of trial participants remains a frequently debated issue, with specific guidance lacking. Trials combining post-trial access and implementation science may necessitate new strategies and models. CAPRISA 008, a post-trial access study testing the feasibility of using family planning services to rollout a prelicensure HIV prevention intervention, tried to balance the real-life scenario of no reimbursement for attendance at public sector clinics with that of a trial including some visits that focused on research procedures and others that focused on standard of care procedures. A reduced reimbursement was offered for 'standard of care' visits, meant primarily to cover transport costs to and from the clinic only. This impacted negatively on accrual, retention and participant morale, primarily due to the protracted delay in regulatory approval, during which time, the costs of living, including travel costs had increased. Relevant guidelines were reviewed and institutional policy was updated to incorporate the South African National Health Research Ethics Committee guidelines on reimbursement (taking into account participant time, travel and inconvenience). The reimbursement amount for 'standard of care' visits was increased accordingly. The question remains whether a trial that combines post-trial access with implementation science, with clear benefits for the participants and the provision of above standard medical care, should have reimbursement rates that approach those of a proof-of-concept trial, for 'standard of care' visits.

An integrated, compact piezohydraulic actuator system for active vibration control was designed and developed with a primary application for gas turbine aircraft engines. Copper tube was chosen as the transmission line material for ease of assembly. Liquid plastic, which meets incompressibility and low-viscosity requirements, was adjusted to provide optimal actuator performance. Variants of the liquid plastic have been prepared with desired properties between −40°F and 400°F. The effectiveness of this hybrid actuator for active vibration control (AVC) was demonstrated for suppressing critical speed vibration through two critical speeds for various levels of intentionally placed imbalance. A high-accuracy closed-loop simulation, which combines both finite element and state space methods, was applied for the closed-loop unbalance response simulation with/without AVC. Good correlation between the simulation and test results was achieved.

Congestive heart failure is a potentially debilitating disorder that affects a significant number of patients. The age-adjusted death rate has doubled over the past decade. Patients live an average of 4 to 5 years, and nearly all suffer from fatigue and breathlessness, which limits exercise capacity and produces a poor quality of life. Patients have usually been advised to avoid exercise because of concerns that they would experience a further decline in cardiac function. However, it has been demonstrated that exercise capacity is not related to the degree of left ventricular systolic dysfunction. This has led to the suggestion that peripheral changes in skeletal muscle and blood supply may play a major role in determining the exercise capacity of patients with congestive heart failure. Studies have demonstrated abnormalities of skeletal muscle blood flow, metabolism and structure, all of which are consistent with the impaired performance observed in these patients. Although the effects of exercise training have been examined in only a relatively few number of patients, the results have been promising. Exercise training has been found to improve exercise capacity and reduce symptoms. However, to our knowledge no data exist as to the impact of exercise training on left ventricular function, hospital stay or mortality in this population. Even though the early results are promising, they require confirmation of feasibility, clinical benefit and safety in larger, long-term randomized trials. It should be determined whether training has a long-term beneficial impact on measures more closely related to daily activities and quality of life. Ultimately, it would be important to determine whether training has an impact on mortality and morbidity.

Modeling of expanding antiretroviral treatment to all HIV infected adults already in care in San Francisco predicts reductions in new HIV infections at 5 years of 59% among men who have sex with men (MSM). Addition of annual HIV testing for MSM to universal treatment decreases new infections by 76%., (See editorial commentary by DeGruttola and Schooley on pages 1050–1052.) Modeling of expanding antiretroviral treatment to all HIV-infected adults already in care in San Francisco predicts reductions in new HIV infection at 5 years of 59% among men who have sex with men. Addition of annual HIV testing for men who have sex with men to universal treatment decreases new infections by 76%.

The experiences of the past 10 years have shown that it is feasible to treat HIV infected patients with ART even in severely resource constrained settings. Achieving the levels of antiretroviral coverage necessary to impact the course of the HIV epidemic remains a challenge and antiretroviral therapy coverage in most nations remains short of even current recommendations. Though treatment as prevention and seek, test, treat and retain strategies are attractive, realization of the benefits of these strategies will require the ability to successfully engage key hard to reach populations such as sex workers. The successes engaging these populations in research settings as seen in the article by Huet et al are encouraging, however key questions remain regarding the sustainability of these efforts as patients are transitioned back to national HIV control programs, many of which are struggling even to maintain the current panels in care in the face declining external funding for HIV care. To achieve the critical goals of increasing treatment uptake and retention and thereby curtail the epidemic of HIV, advocacy from both medicine and public health providers will be critical to generate the support and political will necessary to sustain and enhance the necessary HIV care programs worldwide.

Background. There are few reports of HIV viral load (VL) testing among patients on ART in Vietnam.Methods. From a public clinic in Ho Chi Minh City (HCMC), we reviewed cases of VL measurements from adults on ART.Results. We identified 228 cases. Median age was 30 years (27–34), 85% were male, and 77% had a history of IDU. The mean ART duration was 26 months (95% CI 25–27); d4T/3TC/NVP was the most common regimen. Viral suppression was seen in 160/228 (70%). Viremia (>1000 copies/mL) was associated with prior ART exposure (OR 5.68, ) and immunologic failure (OR 4.69, ). Targeted testing accounted for 13% of cases, only half of which yielded viremia.Conclusion. We demonstrate a high HIV suppression rate among patients on ART in HCMC, Vietnam. In this setting, routine testing detects viremia missed by targeted testing.

Past research on this subject has treated piezoelectric actuators as ideal devices that have tip displacements proportional to their input voltages, at any instant in time. This assumption neglected phase lag and amplitude change at high frequencies. This characteristic of any actuator may lead to coupled control system-structural system instability that limits the amount of active stiffness or active damping that can be obtained. The paper presents a method for simulating the coupled “electromechanical” system to predict rotordynamic stability and unbalance response along with control system stability. The piezoelectric actuators and their amplifiers are represented as equivalent linear electrical circuits. The electromechanical system modeling approach is utilized to correlate test results from a double overhung rotor rig at NASA Lewis. The test results also show the effectiveness of the control system for suppressing the unbalance response of two modes using active stiffness and active damping.

The design of an integrated Russian-VLF/Omega receiver implemented on a TMS320C30-microprocessor-based SPECTRUM plug-in board installed in a PC-compatible portable computer is presented. The system also requires an external antenna, pre-amp, and frequency reference. The SPECTRUM board digitizes the RF signal to 16 b and then digitally mixes with the sines and cosines of the three Russian frequencies plus 10.2, 11-1/3, and 13.6 kHz. The mixer outputs are low-pass filtered, and the comb filters are implemented for the respective epochs. The computer accesses and processes the comb filter outputs, calculating and logging signal phase and amplitude. The design allows for easy future expansion to include unique and VLF communication frequencies. >

Depletional induction therapies are routinely used to prevent acute rejection and improve transplant outcome. The effects of depleting agents on T-cell subsets and subsequent T-cell reconstitution are incompletely defined. We used flow cytometry to examine the effects of rabbit antithymocyte globulin (rATG) on the peripheral T-cell repertoire of pediatric and adult renal transplant recipients. We found that while rATG effectively depleted CD45RA+CD27+ naive and CD45RO+CD27+ central memory CD4+ T cells, it had little effect on CD45RO+CD27− CD4+ effector memory or CD45RA+CD31−, CD45RO+CD27+ and CD45RO+CD27− CD8+ T cell subsets. When we performed a kinetic analysis of CD31+ recent thymic emigrants and CD45RA+/RO+ T cells, we found evidence for both thymopoiesis and homeostatic proliferation contributing to immune reconstitution. We additionally examined the impact of rATG on peripheral CD4+Foxp3+ T cells. We found that in adults, administration of rATG-induced peripheral expansion and new thymic emigration of T cells with a Treg phenotype, while CD4+Foxp3+ T cells of thymic origin predominated in children, providing the first evidence that rATG induces Treg in vivo. Collectively our data indicate that rATG alters the balance of regulatory to memory effector T cells posttransplant, providing an explanation for how it positively impacts transplant outcome.