Nyt fra tidsskrifterne

Wilson B, Perez F, Pan Q, et al.

Novack, Victor; Beitler, Jeremy R.; Yitshak-Sade, Maayan; Thompson, B. Taylor; Schoenfeld, David A.; Rubenfeld, Gordon; Talmor, Daniel; Brown, Samuel M.

Objectives: Survival from acute respiratory distress syndrome is improving, and outcomes beyond mortality may be important for testing new treatments. The “ventilator-free days” score, is an established composite that equates ventilation on day 28 to death. A hierarchical outcome treating death as a worse than prolonged ventilation would enhance face validity, but performance characteristics and reporting of such an outcome are unknown. We therefore evaluated the performance of a novel hierarchical composite endpoint, the Alive and Ventilator Free score. Design: Using data from four Acute Respiratory Distress Syndrome Network clinical trials, we compared Alive and Ventilator Free to the ventilator-free days score. Alive and Ventilator Free compares each patient with every other patient in a win-lose-tie for each comparison. Duration of mechanical ventilation is only compared if both patients survived. We evaluated power of Alive and Ventilator Free versus ventilator-free days score under various circumstances. Setting: ICUs within the Acute Respiratory Distress Syndrome Network. Patients: Individuals enrolled in four Acute Respiratory Distress Syndrome Network trials. Interventions: None for this analysis. Measurements and Main Results: Within the four trials (n = 2,410 patients), Alive and Ventilator Free and ventilator-free days score had similar power, with Alive and Ventilator Free slightly more powerful when a mortality difference was present, and ventilator-free days score slightly more powerful with a difference in duration of mechanical ventilation. Alive and Ventilator Free less often found in favor of treatments that increased mortality and increased days free of ventilation among survivors. Conclusions: A hierarchical composite endpoint, Alive and Ventilator Free, preserves statistical power while improving face validity. Alive and Ventilator Free is less prone to favor a treatment with discordant effects on survival and days free of ventilation. This general approach can support complex outcome hierarchies with multiple constituent outcomes. Approaches to interpretation of differences in Alive and Ventilator Free are also presented. Drs. Novack, Beitler, and Brown were involved in drafting the work. Drs. Yitshak-Sade, Thompson, Schoenfeld, Rubenfeld, and Talmor were involved in critical revision for important intellectual content. Drs. Novack, Beitler, Yitshak-Sade, and Brown were involved in statistical analysis. All authors were involved in substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work. All authors were involved in final approval of the version to be published. All authors were involved in agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Supported, in part, by grant from the National Institutes of Health. Dr. Novack received funding from Cardiomed Consultants LLC. Drs. Beitler’s and Schoenfeld’s institution received funding from the National Institutes of Health (NIH). Drs. Beitler, Thompson, Schoenfeld, and Brown received support for article research from the NIH. Dr. Thompson’s institution received funding from the National Heart, Lung, and Blood Institute (NHLBI) and Department of Defense; reports consulting for Bayer, Boehringer Ingelheim, and GlaxoSmithKline; and authorship for UpToDate, all outside the submitted work. Drs. Talmor (1UM1HL108724) and Beitler (K23HL133489) received funding from NHLBI. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: Samuel.Brown@imail.org Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Lake J, Miller L, Fritz S.

AbstractAntibiotics are frequently prescribed following incision and drainage of cutaneous abscesses. In subgroup analyses from a recent clinical trial, we observed higher likelihood of cure with antibiotic courses beyond five or seven days (up to 10). Among this cohort, for abscesses

Fuentes S, Hahn M, Chilcote K, et al.

AbstractBackgroundRespiratory syncytial virus (RSV) infection causes significant morbidity in hematopoietic cell transplants (HCT) patients. However, antibody response that correlate with recovery from RSV disease are not fully understood.MethodsIn this study, antibody repertoire in paired serum and nasal wash samples from acutely RSV-A infected HCT patients who recovered early (14 days shedding) using gene fragment phage display libraries (GFPDL) and surface plasmon resonance (SPR).ResultsAnti-F serum response were similar between these two groups for antibody repertoires, neutralization titers, anti-F binding antibodies (pre-fusion and post-fusion proteins), antibody avidity and binding to specific antigenic sites. In contrast, nasal washes from early-recovered individuals demonstrated higher binding to F peptide containing p27. While the serum RSV-G antibody repertoires in the two groups were similar, the strongest difference between early-recovered and late-recovered patients was observed in the titers of nasal wash antibodies, especially binding to the central conserved domain (CCD). Most importantly, a significantly higher antibody affinity to RSV-G was observed in nasal washes from early-recovered individuals compared with late-recovered HCT patients.ConclusionsThese findings highlight the importance of mucosal antibodies in resolution of RSV-A infection in the upper respiratory tract.

Fourman, Lindsay T.; Pan, Chelsea S.; Zheng, Isabel; Gerard, Marisa E.; Sheehab, Asia; Lee, Hang; Stanley, Takara L.; Grinspoon, Steven K.

Background: HIV-negative individuals with in utero HIV exposure represent an emerging population, exceeding 18 million people worldwide. Long-term clinical outcomes among HIV-exposed uninfected (HEU) individuals into adolescence and young adulthood remain unknown. Setting: U.S. academic health system. Methods: In this observational cohort study, we leveraged a patient data registry to identify 50 HEU adolescents and young adults. We also identified 141 HIV-unexposed controls that were matched to HEU subjects up to 3:1 on age of last encounter (±2 years), birthdate (±5 years), sex, race/ethnicity, and zip code. All subjects were born since 1/1/1990 with medical records available into adolescence and young adulthood. Primary outcomes were most recent BMI z-score and presence of reactive airway disease (RAD). Records were manually reviewed to extract health information. Results: 50 HEU adolescents and young adults (18±3 years, 54% men) and 141 matched controls (19±3 years, 54% men) were compared. HEU individuals had a higher BMI z-score (1.12±1.08 vs. 0.73±1.09, P=0.03) as well as an increased prevalence of obesity (42% vs. 22%, P=0.009) compared to controls. HEU subjects also had a higher prevalence of RAD versus controls (40% vs. 23%, P=0.03). These differences persisted upon adjusting for demographic, socioeconomic, maternal, and birth-related factors. Maternal prenatal CD4+ T cell count was inversely associated with BMI z-score among HEU adolescents (r=-0.47, P=0.01). Conclusion: HEU adolescents and young adults exhibited a heightened prevalence of obesity and RAD compared to HIV-unexposed controls. Additional studies are needed to optimize care for the expanding population of HEU individuals transitioning to adulthood. Corresponding Author: Steven K. Grinspoon Professor of Medicine, Harvard Medical School MGH Endowed Chair in Neuroendocrinology and Metabolism Chief, Metabolism Unit Massachusetts General Hospital 55 Fruit Street 5LON207 Boston, MA 02114 Phone: 617-724-9109 Fax: 617-724-8998 Email: sgrinspoon@mgh.harvard.edu Conflicts of Interest and Sources of Support: Sources of funding for this work were NIH 1KL2TR002542-01 (L.T.F.) and NIH P30 DK040561 (S.K.G.). S.K.G. has served as a consultant for Theratechnologies, and has received grant support from Theratechnologies, Gilead, and Kowa Pharmaceuticals, all unrelated to this manuscript. T.L.S. has received funding from Novo Nordisk for an investigator-initiated grant, also unrelated to the current project. L.T.F., C.S.P., I.Z., M.E.G., A.S., and H.L. have no conflicts of interest to disclose. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Abstract Background Adjustment of immunosuppression is the main therapy for BK polyomavirus (BKPyV)-associated nephropathy (BKPyVAN) after kidney transplantation (KT). Studies of BKPyV-specific T cell immune response are scarce. Here, we investigated BKPyV-specific T cell immunity in KT recipients diagnosed with BKPyVAN. Methods All adult KT recipients with BKPyVAN diagnosed at our institution from January 2017 to April 2018 were included. Laboratory-developed intracellular cytokine assays measuring the percentage of IFN-γ-producing CD4+ and CD8+ T cells, after stimulation with large-T antigen (LT) and viral capsid protein 1 (VP1), were performed both at the time of diagnosis and after adjustment of immunosuppression. Results We included 12 KT recipients diagnosed with BKPyVAN (7 proven, 4 presumptive, and 1 possible). Those with presumptive BKPyVAN had a median plasma BKPyV DNA load of 5.9 log10 copies/ml (interquartile range [IQR]: 4.9–6.1). Adjusted dosing of mycophenolic acid and tacrolimus with (86%) or without (14%) adjunctive therapies were implemented after diagnosis. There was a significantly higher median percentage of IFN-γ-producing CD4+ T cells to LT at a median of 3 (IQR: 1–4) months after adjustment of immunosuppression compared with at the time of diagnosis (0.004 vs. 0.015; p = 0.047). However, the difference between the median percentage of IFN-γ-producing CD4+ T cells to VP1 and CD8+ T cells to LT and VP1 did not reach statistical significance. Four (33%) patients achieved plasma BKPyV DNA clearance, and the remaining eight (67%) patients had persistent BKPyV DNAemia. Although eight (67%) patients developed allograft dysfunction, none required hemodialysis. Conclusions We observed a marginal trend of BKPyV-specific CD4+ T cell recovery after adjustment of immunosuppression in KT recipients diagnosed with BKPyVAN. A further study would be benefited to confirm and better assess BKPyV-specific immune response after KT.…

The original version of this article unfortunately contained a mistake. The presentation of Fig. 1 was incorrect. The corrected figure is given below.…

Lansbury, Louise E.; Rodrigo, Chamira; Leonardi-Bee, Jo; Nguyen-Van-Tam, Jonathan; Lim, Wei Shen

Objectives: Corticosteroids may be beneficial in sepsis, but uncertainty remains over their effects in severe influenza. This systematic review updates the current evidence regarding corticosteroids in the treatment of influenza and examines the effect of dose on outcome. Data Sources: Electronic databases (MEDLINE, EMBASE, CINAHL, LILACS, CENTRAL, and Web of Science) and trial registries were searched to October 2018 for randomized controlled trials, quasi-experimental designs, and observational cohort studies reporting corticosteroid versus no corticosteroid treatment in individuals with influenza. Study Selection and Data Extraction: Two researchers independently assessed studies for inclusion. Risk of bias was assessed using the Cochrane Risk of Bias tool (randomized controlled trials) or Newcastle-Ottawa Scale (observational studies). Where appropriate, we estimated the effect of corticosteroids by random-effects meta-analyses using the generic inverse variance method. Meta-regression analysis was used to assess the association of corticosteroid dose and mortality. Data Synthesis: We identified 30 eligible studies, all observational apart from one randomized controlled trial. Twenty-one observational studies were included in the meta-analysis of mortality, which suggested an adverse association with corticosteroid therapy (odds ratio, 3.90; 95% CI, 2.31–6.60; 15 studies; adjusted hazard ratio, 1.49; 95% CI, 1.09–2.02; six studies). Risk of bias assessment was consistent with potential confounding by indication. Pooled analysis of seven studies showed increased odds of hospital-acquired infection in people treated with corticosteroids (unadjusted odds ratio, 2.74; 95% CI, 1.51–4.95). Meta-regression of the effect of dose on mortality did not reveal an association, but reported doses of corticosteroids in included studies were high (mostly > 40 mg methylprednisolone [or equivalent] per day). Conclusions: Corticosteroid treatment in influenza is associated with increased mortality and hospital-acquired infection, but the evidence relates mainly to high corticosteroid doses and is of low quality with potential confounding by indication a major concern. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Supported, in part, by grants from National Institute for Health Research Nottingham Biomedical Research Centre, (Nottingham University Hospitals National Health Service Trust and University of Nottingham), Nottingham, United Kingdom. This article is based on a Cochrane Review published in the Cochrane Database of Systematic Reviews (CDSR) 2019; issue 2, DOI: 10.1002/14651858.CD010406. (see www.cochranelibrary.com for information). Cochrane Reviews are regularly updated as new evidence emerges and in response to feedback, and the CDSR should be consulted for the most recent version of the review. Dr. Lansbury disclosed that this work is part of an ongoing program undertaken by the Nottingham Biomedical Research Centre funded by the National Institute for Health Research (NIHR); she is the Head of the World Health Organization Collaborating Centre for Pandemic Influenza and Research at the University of Nottingham, which has a grant from the World Health Organization to provide technical assistance for the prevention and control of seasonal influenza; she has salary support funded by the NIHR; and she received support for article research from the NIHR. Dr. Rodrigo received salaries funded, in part, by an unrestricted grant from Pfizer and the NIHR. Professor Leonardi-Bee disclosed that she was a coapplicant on an educational grant from Hoffmann-La Roche to carry out research in the area of pandemic influenza. Hoffmann-La Roche did not support any aspects of this work. She also undertook consultancy work for the U.K. Food Standards Agency in 2013–2015 and for a Breast Milk Substitute manufacturer in 2017 to help them design a healthcare claim trial. Professor Nguyen-Van-Tam’s institution received funding from the NIHR. He disclosed that the University of Nottingham Health Protection Research Group currently holds an unrestricted educational grant for influenza research from F. Hoffmann-La Roche, but this did not support any aspect of this work. He also disclosed that he is a former employee of SmithKline Beecham plc (now GlaxoSmithKline), Roche Products, and Aventis-Pasteur MSD (now Sanofi-Pasteur MSD), all prior to 2005, with no outstanding pecuniary interests by way of shareholdings, share options, or accrued pension rights. He is currently on secondment to the Department of Health and Social Care (U.K. government); he received support for article research from NIHR, Nottingham Biomedical Research Centre; and he disclosed off-label product use of corticosteroids. Professor Lim’s institution received funding from NIHR Biomedical Research Centre and Pfizer (unrestricted investigator-initiated research grant for pneumococcal pneumonia) and the NIHR (corticosteroids in pandemic influenza clinical trial). This work was performed at the University of Nottingham, Nottingham, United Kingdom. Address requests for reprints to: Louise E. Lansbury, MBBS, PhD, Department of Epidemiology and Public Health, University of Nottingham, Room B104 Clinical Sciences Building, City Hospital, Nottingham NG5 1PB, United Kingdom. E-mail: louise.lansbury@nottingham.ac.uk Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Abstract Background Rabies is estimated to cause 59,000 deaths and economic losses of US$8.6 billion every year. Despite several years of rabies surveillance and awareness programmes, increased availability of post-exposure prophylaxis vaccinations and dog population control, the disease still remains prevalent in Sri Lanka. This study reports the roll-out of a high number, high coverage canine rabies vaccination campaign in Sri Lanka, providing estimates for the vaccination coverage achieved, analysing the local dog demographics, and identifying barriers of attendance to static vaccination clinics. Methods A mass dog vaccination campaign was undertaken in Negombo, Sri Lanka. The campaign was composed of static point and door-to-door vaccination stages, with a final survey of vaccination coverage. A large volume of data on the distribution, health, and signalment of vaccinated dogs was collected through a mobile phone application. A logistic regression model was developed to investigate which socio-spatial and dog-related factors influenced attendance of owners to static vaccination points. Results The campaign vaccinated over 7800 dogs achieving a vaccination coverage of 75.8%. A dog:human ratio of 1:17 was estimated. Most dogs were owned, and the dog population was mostly male, adult, and non-sterilized. Unawareness, unavailability and handling problems were the most common reasons given by owners to explain failure to attend a static vaccination point. The regression analysis showed that increasing distance to a static point, in addition to young age and poor health of the dog, were associated with a decrease in the likelihood of attendance to a static vaccination points. Conclusion This study demonstrates the feasibility of high number, high coverage vaccination campaigns in Sri Lanka. The information on dog ecology and barriers of attendance to static point vaccination clinics will facilitate development of future vaccination campaigns.…

Abstract Background Diabetes is one of the underlying risk factors for developing community-acquired pneumonia (CAP). The high prevalence of diabetes among population and the rising incidence of this illness, converts it as an important disease to better control and manage, to prevent its secondary consequences as CAP. The objective of this research is to describe the characteristics of the patients with diabetes and the differences with the no diabetes who have had an episode of CAP in the context of the primary care field. Methods A retrospective, observational study in adult patients (> 18 years-old) who suffer from CAP and attended at primary care in Spain between 2009 and 2013 was developed using the Computerized Database for Pharmacoepidemiological Studies in Primary Care (BIFAP). We carried out a descriptive analysis of the first episodes of CAP, in patients with or without diabetes as comorbidity. Other morbidity (CVA, Anaemia, Arthritis, Asthma, Heart disease, Dementia, Depression, Dysphagia, Multiple sclerosis, Epilepsy, COPD, Liver disease, Arthrosis, Parkinson’s disease, Kidney disease, HIV) and life-style factors were also included in the study. Results A total of 51,185 patients were included in the study as they suffer from the first episode of CAP. Of these, 8012 had diabetes as comorbidity. There were differences between sex and age in patients with diabetes. Patients without diabetes were younger, and had less comorbidities including those related to lifestyles such as smoking, alcoholism, social and dental problems than patients with diabetes. Conclusions Patients who developed an episode of CAP with diabetes have more risk factors which could be reduced with an appropriate intervention, including vaccination to prevent successive CAP episodes and hospitalization. The burden of associated factors in these patients can produce an accumulation of risk. Health care professional should know this for treating and control these patients in order to avoid complications. Diabetes and those other risk factors associated could be reduced with an appropriate intervention, including vaccination to prevent the first and successive CAP episodes and the subsequent hospitalization in severe cases.…

Shields R, McCreary E, Marini R, et al.

AbstractTwenty patients with carbapenem-resistant Enterobacteriaceae (CRE) infections were treated with meropenem-vaborbactam. Thirty-day clinical success and survival rates were 65% (13/20) and 90% (18/20), respectively. Thirty-five percent of patients had microbiologic failures within 90 days. One patient developed a recurrent infection due to meropenem-vaborbactam non-susceptible, ompK36 porin mutant Klebsiellapneumoniae.

File T, Jr, Bleasdale S.

Greene, Rebecca A.; Zullo, Andrew R.; Mailloux, Craig M.; Berard-Collins, Christine; Levy, Mitchell M.; Amass, Timothy

Objectives: To determine whether best practice advisories improved sedation protocol compliance and could mitigate potential propofol-related hazardous conditions. Design: Retrospective observational cohort study. Setting: Two adult ICUs at two academic medical centers that share the same sedation protocol. Patients: Adults 18 years old or older admitted to the ICU between January 1, 2016, and January 31, 2018, who received a continuous infusion of propofol. Interventions: Two concurrent best practice advisories built in the electronic health record as a clinical decision support tool to enforce protocol compliance with triglyceride and lipase level monitoring and mitigate propofol-related hazardous conditions. Measurements and Main Results: The primary outcomes were baseline and day 3 compliance with triglyceride and lipase laboratory monitoring per protocol and time to discontinuation of propofol in the setting of triglyceride and/or lipase levels exceeding protocol cutoffs. A total of 1,394 patients were included in the study cohort (n = 700 in the pre–best practice advisory group; n = 694 in the post–best practice advisory group). In inverse probability weighted regression analyses, implementing the best practice advisory was associated with a 56.6% (95% CI, 52.6–60.9) absolute increase and a 173% relative increase (risk ratio, 2.73; 95% CI, 2.45–3.04) in baseline laboratory monitoring. The best practice advisory was associated with a 34.0% (95% CI, 20.9–47.1) absolute increase and a 74% (95% CI, 1.39–2.19) relative increase in day 3 laboratory monitoring after inverse probability weighted analyses. Among patients with laboratory values exceeding protocol cutoffs, implementation of the best practice advisory resulted in providers discontinuing propofol an average of 16.6 hours (95% CI, 4.8–28.3) sooner than pre–best practice advisory. Findings from alternate analyses using interrupted time series were consistent with the inverse probability weighted analyses. Conclusions: Best practice advisories can be effectively used in ICUs to improve sedation protocol compliance and may mitigate potential propofol-related hazardous conditions. Best practice advisories should undergo continuous quality assurance and optimizations to maximize clinical utility and minimize alert fatigue. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Dr. Zullo is supported by award 5K12HS022998 from the Agency for Healthcare Research and Quality. He is supported, in part, by a research grant from Sanofi Pasteur to Brown University on unrelated work that aims to understand the epidemiology of infections in long-term care facilities. He is also supported by a Department of Veterans Affairs Office of Academic Affiliations Advanced Fellowship in Health Services Research and Development. Dr. Amass’ institution received funding from National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (grant number: T32HL134625), and the Brown University Respiratory Research Training Program, and he received support for article research from the NIH. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: rgreene1@lifespan.org Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Guan X, Che Y, Wei S, et al.

AbstractBackgroundEvaluation of a licensed inactivated EV71 vaccine is needed in a phase IV study with a large population to identify its effectiveness and safety for further application.MethodsAn open-label and controlled trial involving a large population of 155,995 children aged 6-71 months is performed; 40,724 were enrolled in the vaccine group and received 2 doses of inactivated EV71 vaccine at an interval of 1 month, and the remaining children were used as the control group. The EV71-infected hand, foot and mouth disease (HFMD) cases were monitored in the vaccine and control groups during a follow-up period of 14 months since the 28th days post inoculation through the local database of Notifiable Infectious Diseases Network. The effectiveness of the vaccine was estimated by comparing the incidence density in the vaccine group versus that in the control group based upon EV71 infected patients identified via laboratory testing. In parallel, the active and passive surveillance for safety of the vaccine was conducted by home or telephone visits and by using the Adverse Event Following Immunization (AEFI) system, respectively.ResultsAn overall level of 89.7% (95% confidence interval [CI], 24.0 to 98.6) vaccine effectiveness (VE) against EV71 infection and a 4.58% rate of reported AEs were observed. Passive surveillance demonstrated a 0.31% rate of reported common minor reactions.ConclusionsThe clinical protection and safety of the EV71 vaccine were demonstrated in the immunization of a large population.Clinical trials registrationNCT03001986.

Abstract Background The current evidence of extra length of stay (LOS) attributable to healthcare-associated infection (HCAI) scarcely takes time-dependent bias into consideration. Plus, limited evidences were from developing countries. We aim to estimate the extra LOS and risk factors of mortality attributable to HCAI for inpatients. Methods Multi-state model (MSM) was adopted to estimate the extra LOS attributable to HCAI of each type and subgroup. COX regression model was used to examine the risk of mortality. Results A total of 51,691 inpatients were included and 1709 (3.31%) among them developed HCAI. Lower respiratory tract infection and Acinetobacter baumannii were the most prevalent HCAI and causative pathogen in surveyed institute. Generally, the expected extra LOS attributable to HCAI was 2.56 days (95% confidence interval: 2.54–2.61). Patients below 65 had extra LOS attributable to HCAI longer about 2 days than those above. The extra LOS attributable to HCAI of male patients was 1.33 days longer than female. Meanwhile, age above 65 years old and HCAI were the risk factors of mortality for inpatients. Conclusions HCAI contributes to an increase in extra LOS of inpatients in China. The effect of HCAI on extra LOS is different among subgroups, with the age below 65, male and medicine department more sensitive.…

McManus K, Christensen B, Nagraj V, et al.

AbstractBackgroundHealthcare delivery changes associated with viral suppression (VS) could contribute to the United States’ “Ending the HIV Epidemic” (EtHE) initiative. This study aims to determine whether Qualified Health Plans (QHPs) purchased by AIDS Drug Assistance Programs (ADAPs) are associated with VS for low-income people living with HIV (PLWH) across three states.MethodsA multistate cohort of ADAP clients who were eligible for ADAP-funded QHPs were studied (2014-2015). A log-binomial model was used to estimate the association of demographics and healthcare delivery factors with QHP enrollment prevalence and one-year risk of VS. A number needed to treat/enroll (NNT) for one additional person to achieve viral suppression was calculated.ResultsOf the cohort (n=7776), 52% enrolled in QHPs. QHP enrollment in 2015 was associated with QHP coverage in 2014 (adjusted prevalence ratio [aPR] 3.28; 95% confidence interval 3.06-3.53) and engagement in care in 2014 (aPR 1.16; 1.04-1.28).PLWH who were engaged in care (n=4597) and had QHPs had a higher VS rate than those who received medications from Direct ADAP (86.0% vs. 80.2%). QHPs’ NNT for an additional person to achieve VS is 20 (14.1-34.5). Starting undetectable (adjusted risk ratio [aRR] 1.39; 1.28-1.52) and enrolling in QHPs in 2015 (aRR 1.06; 0.99-1.14) was associated with VS.ConclusionsOnce enrolled in ADAP-funded QHPs, ADAP clients stay enrolled. Enrollment is associated with VS across states and demographic groups. ADAPs, especially in the South and in Medicaid non-expansion states, should consider investing in QHPs because increased enrollment could improve VS rates. This evidence-based intervention could be a part of EtHE.

Amass, Timothy H.; Villa, Gianluca; OMahony, Sean; Badger, James M.; McFadden, Rory; Walsh, Thomas; Caine, Tanis; McGuirl, Don; Palmisciano, Amy; Yeow, Mei-Ean; De Gaudio, Raffaele; Curtis, J. Randall; Levy, Mitchell M.

Objectives: To assess the feasibility and efficacy of implementing “Family Care Rituals” as a means of engaging family members in the care of patients admitted to the ICU with a high risk of ICU mortality on outcomes including stress-related symptoms in family members. Design: Prospective, before-and-after intervention evaluation. Setting: Two U.S. academic medical ICU’s, and one Italian academic medical/surgical ICU. Subjects: Family members of patients who had an attending predicted ICU mortality of greater than 30% within the first 24 hours of admission. Interventions: A novel intervention titled “Family Care Rituals” during which, following a baseline observation period, family members enrolled in the intervention phase were given an informational booklet outlining opportunities for engagement in care of the patient during their ICU stay. Measurements and Main Results: Primary outcome was symptoms of post-traumatic stress disorder in family members 90 days after patient death or ICU discharge. Secondary outcomes included symptoms of depression, anxiety, and family satisfaction. At 90-day follow-up, 131 of 226 family members (58.0%) responded preintervention and 129 of 226 family members (57.1%) responded postintervention. Symptoms of post-traumatic stress disorder were significantly higher preintervention than postintervention (39.2% vs 27.1%; unadjusted odds ratio, 0.58; p = 0.046). There was no significant difference in symptoms of depression (26.5% vs 25.2%; unadjusted odds ratio, 0.93; p = 0.818), anxiety (41.0% vs 45.5%; unadjusted odds ratio, 1.20; p = 0.234), or mean satisfaction scores (85.1 vs 89.0; unadjusted odds ratio, 3.85; p = 0.052) preintervention versus postintervention 90 days after patient death or ICU discharge. Conclusions: Offering opportunities such as family care rituals for family members to be involved with providing care for family members in the ICU was associated with reduced symptoms of post-traumatic stress disorder. This intervention may lessen the burden of stress-related symptoms in family members of ICU patients. This research was completed at following institutions: Rhode Island Hospital, Rush Medical Center, Azienda Ospedaliero-Universitaria Careggi. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). The James M Cox Foundation provide support for this trial in the form of grant funding for study coordination, travel, supplies, and statistical analysis. Dr. Amass’s institution received funding from the National Heart, Lung, and Blood Institute (grant T32 HL134625), and he received support for article research from the National Institutes of Health. Drs. Amass’s, OMahoney’s, Caine’s, and Palmisciano’s institutions received funding from the James M. Cox Foundation. Dr. Villa received funding from Baxter and Pall. Dr. OMahoney received support for article research from the Family Foundation Grant. Ms. McFadden, Mr. Walsh, Ms. Caine, and Ms. Palmisciano received support for article research from James M. Cox Foundation. Dr. De Gaudio’s institution received funding from MSD Italia and Pall, and he received funding from Baxter. The remaining authors have disclosed that they do not have any potential conflicts of interest. Address requests for reprints to: Timothy H. Amass, MD, ScM, Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado School of Medicine. Department of Veterans Affairs, Eastern Colorado Health System. 1700 N. Wheeling Street, Office F2-266, Denver, CO 80045 E-mail: tim.amass@gmail.com Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Itagaki, Kiyoshi; Kaczmarek, Elzbieta; Kwon, Woon Yong; Chen, Li; Vlková, Barbora; Zhang, Quanzhi; Riça, Ingred; Yaffe, Michael B.; Campbell, Yan; Marusich, Michael F.; Wang, Ji Ming; Gong, Wang-Hua; Gao, Ji-Liang; Jung, Françoise; Douglas, Garry; Otterbein, Leo E.; Hauser, Carl J.

Objectives: Trauma predisposes to systemic sterile inflammation (systemic inflammatory response syndrome) as well as infection, but the mechanisms linking injury to infection are poorly understood. Mitochondrial debris contains formyl peptides. These bind formyl peptide receptor-1, trafficking neutrophils to wounds, initiating systemic inflammatory response syndrome, and wound healing. Bacterial formyl peptides, however, also attract neutrophils via formyl peptide receptor-1. Thus, mitochondrial formyl peptides might suppress neutrophils antimicrobial function. Also, formyl peptide receptor-1 blockade used to mitigate systemic inflammatory response syndrome might predispose to sepsis. We examined how mitochondrial formyl peptides impact neutrophils functions contributing to antimicrobial responses and how formyl peptide receptor-1 antagonists affect those functions. Design: Prospective study of human and murine neutrophils and clinical cohort analysis. Setting: University research laboratory and level 1 trauma center. Patients: Trauma patients, volunteer controls. Animal Subjects: C57Bl/6, formyl peptide receptor-1, and formyl peptide receptor-2 knockout mice. Interventions: Human and murine neutrophils functions were activated with autologous mitochondrial debris, mitochondrial formyl peptides, or bacterial formyl peptides followed by chemokines or leukotrienes. The experiments were repeated using formyl peptide receptor-1 antagonist cyclosporin H, “designer” human formyl peptide receptor-1 antagonists (POL7178 and POL7200), or anti-formyl peptide receptor-1 antibodies. Mouse injury/lung infection model was used to evaluate effect of formyl peptide receptor-1 inhibition. Measurements and Main Results: Human neutrophils cytosolic calcium, chemotaxis, reactive oxygen species production, and phagocytosis were studied before and after exposure to mitochondrial debris, mitochondrial formyl peptides, and bacterial formyl peptides. Mitochondrial formyl peptide and bacterial formyl peptides had similar effects on neutrophils. Responses to chemokines and leukotrienes were suppressed by prior exposure to formyl peptides. POL7200 and POL7178 were specific antagonists of human formyl peptide receptor-1 and more effective than cyclosporin H or anti-formyl peptide receptor-1 antibodies. Formyl peptides inhibited mouse neutrophils responses to chemokines only if formyl peptide receptor-1 was present. Formyl peptide receptor-1 blockade did not inhibit neutrophils bacterial phagocytosis or reactive oxygen species production. Cyclosporin H increased bacterial clearance in lungs after injury. Conclusions: Formyl peptides both activate and desensitize neutrophils. Formyl peptide receptor-1 blockade prevents desensitization, potentially both diminishing systemic inflammatory response syndrome and protecting the host against secondary infection after tissue trauma or primary infection. This work was performed at Beth Israel Deaconess Medical Center. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Supported, in part, by Department of Defense Focused Program Award W81XWH-16-1-0464 (Drs. Yaffe, Otterbein, and Hauser) and National Institute of Allergy Infectious Diseases grant 1R03AI35346-01 (Dr. Itagaki). Dr. Itagaki has a grant from National Institute of Allergy and Infectious Diseases/National Institutes of Health (NIH), 1R03AI135346-01. Drs. Itagaki, Kaczmarek, Wang, Gong, Gao, and Otterbein received support for article research from the NIH. Dr. Yaffe’s institution received funding from Department of Defense (DoD); he received funding from The American Association for the Advancement of Science Science Signaling and Applied Biomath; and he received support for article research from the DoD. Drs. Wang, Gong, and Gao disclosed government work. Dr. Otterbein received funding from HillHurst Biopharmaceuticals (stock options). Drs. Hauser and Otterbein share a grant from DoD, W81XWH-16-1-0464. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: kitagaki@bidmc.harvard.edu; cjhauser@bidmc.harvard.edu Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Terveer E, , van Gool T, et al.

AbstractBackgroundPatients with multiple recurrent Clostridioides difficile infections (rCDI) are treated with fecal microbiota transplantation (FMT) provided by healthy donors. Blastocystis colonization of donors is considered an exclusion criterion, whereas its pathogenicity is still under debate.MethodsThe introduction of molecular screening for Blastocystis sp. at our stool bank identified two donors with prior negative microscopy but positive PCR. Potential transmission of Blastocystis sp. to patients was assessed on 16 fecal patient samples, pre- and post-FMT, by PCR and subtype (ST) analysis. In addition, clinical outcome for treatment of rCDI (n=31), as well as development of gastrointestinal symptoms was assessed.ResultsOne donor carried Blastocystis ST1, the other contained ST3. All patients tested Blastocystis negative prior to FMT. With a median of 20.5 days after FMT, 8 of 16 (50%) patients developed intestinal colonization with Blastocystis, with identical ST-sequences as their respective donors. Blastocystis containing fecal suspensions were used to treat 31 rCDI patients, with a FMT success rate of 84%. This success rate was not statistically different from patients transferred with Blastocystis sp. negative donor feces (93%, 76/82). Patients transferred with Blastocystis sp. positive donor feces did not report any significant difference in bowel complaints in the first week, after 3 weeks and the months following FMT.ConclusionsWe demonstrated the first transmission of Blastocystis ST1 and ST3 from donor to patients by FMT. This did not result in gastrointestinal symptomatology or have any significant effect on rCDI treatment outcome.

Sharma R, Singh P, McCoy R, et al.

AbstractBackgroundMycobacterium leprae was thought the exclusive causative agent of leprosy until Mycobacterium lepromatosis was identified in a rare form of leprosy known as diffuse lepromatous leprosy (DLL).MethodsWe isolated M. lepromatosis from a patient with DLL and propagated it in athymic nude mouse footpads. Genomic analysis of this strain (NHDP-385) identified a unique repetitive element, RLPM, upon which a specific real-time quantitative PCR (qPCR) assay was developed. The RLPM assay, and our previously developed RLEP qPCR for M. leprae, were validated as clinical diagnostic assays according to Clinical Laboratory Improvement Amendments guidelines. We tested DNA from archived histological sections, patient specimens from the United States (US), Philippines, and Mexico, and US wild armadillos.ResultsThe limit of detection for the RLEP and RLPM assays is 30 M. leprae per specimen (0.76 bacilli per reaction; CV%: 0.65-2.44) and 122 M. lepromatosis per specimen (3.05 bacilli per reaction; CV%: 0.84-2.9), respectively. In histological sections (n=10), one lepromatous leprosy (LL), one DLL, and three Lucio reactions contained M. lepromatosis; two LL and two Lucio reactions contained M. leprae; one LL contained both species. M. lepromatosis was detected in 3/218 (1.38%) US biopsies. All Philippines specimens (n=180) were M. lepromatosis negative and M. leprae positive. Conversely, 15/47 (31.91%) Mexican specimens were positive for M. lepromatosis; 19/47 (40.43%) were positive for M. leprae; 2/47 (4.26%) contained both organisms. All armadillos were M. lepromatosis negative.ConclusionsThe RLPM and RLEP assays will aid healthcare providers in clinical diagnosis and surveillance of leprosy.

Boettiger D.

Smit M, Perez-Guzman P, Mutai K, et al.

AbstractBackgroundThe non-communicable disease (NCD) burden in Kenya is not well characterised, despite estimates needed to identify future health priorities. We aim to quantify current and future NCD burden in Kenya by HIV status.MethodsOriginal systematic reviews (SRs) and meta-analyses of prevalence/incidence of cardiovascular disease (CVD), chronic kidney disease, depression, diabetes, high total cholesterol, hypertension, human papillomavirus infection and related pre-cancerous stages in Kenya were carried out. An individual-based model was developed, simulating births, deaths, HIV-disease and treatment, aforementioned NCDs and cancers. The model was parameterised using SR, epidemiological national and regional surveillance data. NCD burden was quantified for 2018-2035 by HIV status amongst adults.FindingsSRs identified prevalence/incidence data for each NCD, except ischemic heart disease. The model estimates that 51% of Kenyan adults currently suffer from ≥1 NCD, with a higher burden in People Living with HIV (PLHIV) compared to HIV-negative (62% versus 51%), driven by their higher age profile and partly by HIV-related risk for NCDs. Hypertension and high total cholesterol are the main NCD drivers (adult prevalence of 20·5% (5·3 million) and 9·0% (2·3 million)), with CVD and cancers the main causes of death. The burden is projected to increase by 2035 (56% in HIV-negative; 71% in PLHIV), with population growth doubling the number of people needing services (15·4 million to 28·1 million) by 2035.ConclusionsNCD services will need to be expanded in Kenya. Guidelines in Kenya already support provision of these amongst both the general and HIV-positive population, however coverage remains low.

Stewart A, Harris P, Chatfield M, et al.

AbstractTreatment options for multidrug resistant (MDR) Gram-negative infection are growing. However, post-registration, pragmatic and clinician-led clinical trials in this field are few, recruit small sample sizes, and experience deficiencies in design and operations. MDR Gram-negative therapeutic trials are often inefficient, only evaluating a single antibiotic or strategy at a time. Novel clinical trial designs offer potential solutions by attempting to obtain clinically meaningful conclusions at the end or during a trial, for many treatment strategies, simultaneously. An integrated, consensus approach to multidrug resistant Gram-negative infection trial design is crucial.

Puksuriwong S, Ahmed M, Sharma R, et al.

AbstractIncreasing evidences support a critical role of CD8+ T cell immunity against influenza. Activation of mucosal CD8+T cells, particularly tissue-resident memory T(TRM) cells recognizing conserved epitopes would mediate rapid and broad protection. Matrix protein 1(M1) is a well-conserved internal protein. We studied the capacity of Modified Vaccinia Ankara-vectored vaccine expressing nucleoprotein(NP) and M1(MVA-NP+M1) to activate M1-specific CD8+ T cell response including TRM cells in nasopharynx-associated lymphoid tissue(NALT) from children and adults. Following MVA-NP+M1 stimulation, M1 was abundantly expressed in adenotonsillar epithelial cells and B cells. MVA-NP+M1 activated marked IFN-γ-secreting T cell response to M1 peptides. Using tetramer staining, we showed the vaccine activated a marked increase in M158-66-specific CD8+ T cells in tonsillar mononuclear cells (MNC) of HLA-matched individuals. We also demonstrated MVA-NP+M1 activated a substantial increase in TRM cells exhibiting effector memory T cell phenotype. Upon recall antigen recognition, M1-specific T cells rapidly undergo cytotoxic degranulation, release granzyme B and pro-inflammatory cytokines, leading to target cell killing. Conclusion: MVA-NP+M1 elicits a substantial M1-specific T cell response including TRM cells in NALT, demonstrating its strong capacity to expand memory T cell pool exhibiting effector memory T cell phenotype, therefore offering great potential for rapid and broad protection against influenza reinfection.

Maciel, Carolina B.; Barden, Mary M.; Youn, Teddy S.; Dhakar, Monica B.; Greer, David M.

Objectives: To characterize approaches to neurologic outcome prediction by practitioners who assess prognosis in unconscious cardiac arrest individuals, and assess compliance to available guidelines. Design: International cross-sectional study. Setting: We administered a web-based survey to members of Neurocritical Care Society, Society of Critical Care Medicine, and American Academy of Neurology who manage unconscious cardiac arrest patients to characterize practitioner demographics and current neuroprognostic practice patterns. Subjects: Physicians that are members of aforementioned societies who care for successfully resuscitated cardiac arrest individuals. Interventions: Not applicable. Measurements and Main Results: A total of 762 physicians from 22 countries responses were obtained. A significant proportion of respondents used absent corneal reflexes (33.5%) and absent pupillary reflexes (36.2%) at 24 hours, which is earlier than the recommended 72 hours in the standard guidelines. Certain components of the neurologic examination may be overvalued, such as absent motor response or extensor posturing, which 87% of respondents considered being very or critically important prognostic indicators. Respondents continue to rely on myoclonic status epilepticus and neuroimaging, which were favored over median nerve somatosensory evoked potentials for prognostication, although the latter has been demonstrated to have a higher predictive value. Regarding definitive recommendations based on poor neurologic prognosis, most physicians seem to wait until the postarrest timepoints proposed by current guidelines, but up to 25% use premature time windows. Conclusions: Neuroprognostic approaches to hypoxic-ischemic encephalopathy vary among physicians and are often not consistent with current guidelines. The overall inconsistency in approaches and deviation from evidence-based recommendations are concerning in this disease state where mortality is so integrally related to outcome prediction. Drs. Maciel and Barden contributed equally for this article and shared first authorship. This study was conducted at Yale University School of Medicine. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Dr. Maciel received funding from Claude D. Pepper Older Americans Independence Center Junior Scholar award that supports preclinical studies of mechanisms of secondary brain injury in a rodent cardiac arrest model. Dr. Dhakar received funding from Adamas Pharmaceuticals and research support from Marinus Pharmaceuticals and UCB Biopharma for clinical trials. Dr. Greer’s institution received funding from National Institutes of Neurological Disorders and Stroke/National Institutes of Health, he received funding form medical-legal consultation, and he serves as Editor-in-Chief of Seminars in Neurology and has received compensation for medico-legal consultation. The remaining authors have disclosed that they do not have any potential conflicts of interest. ORCID 0000-0002-8763-5839 (to Dr. Maciel), ORCID 0000-0002-4901-4177 (to Dr. Barden), ORCID 0000-0002-7325-1148 (to Dr. Youn), ORCID 0000-0001-9275-2784 (to Dr. Dhakar), and ORCID 0000-0002-2026-8333 (to Dr. Gree). For information regarding this article, E-mail: carolina.maciel@neurology.ufl.edu Copyright © by 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Agan B, Marconi V.

human immunodeficiency virusantiretroviral therapynon-communicable diseasesub-Saharan AfricaKenya…

Abstract Background Diagnosing pneumonia can be challenging in general practice but is essential to distinguish from other respiratory tract infections because of treatment choice and outcome prediction. We determined predictive signs, symptoms and biomarkers for the presence of pneumonia in patients with acute respiratory tract infection in primary care. Methods From March 2012 until May 2016 we did a prospective observational cohort study in three radiology departments in the Leiden-The Hague area, The Netherlands. From adult patients we collected clinical characteristics and biomarkers, chest X ray results and outcome. To assess the predictive value of C-reactive protein (CRP), procalcitonin and midregional pro-adrenomedullin for pneumonia, univariate and multivariate binary logistic regression were used to determine risk factors and to develop a prediction model. Results Two hundred forty-nine patients were included of whom 30 (12%) displayed a consolidation on chest X ray. Absence of runny nose and whether or not a patient felt ill were independent predictors for pneumonia. CRP predicts pneumonia better than the other biomarkers but adding CRP to the clinical model did not improve classification (− 4%); however, CRP helped guidance of the decision which patients should be given antibiotics. Conclusions Adding CRP measurements to a clinical model in selected patients with an acute respiratory infection does not improve prediction of pneumonia, but does help in giving guidance on which patients to treat with antibiotics. Our findings put the use of biomarkers and chest X ray in diagnosing pneumonia and for treatment decisions into some perspective for general practitioners.…

Dickstein Y, Leibovici L, Carmeli Y, et al.

Wiese A, Greevy R, Jr, Grijalva C.

Goff D, Mangino J, Glassman A, et al.

AbstractDentists prescribe 10% of all outpatient antibiotic prescriptions, writing more than 25.7 million prescriptions per year. Many are for prophylaxis in patients with prosthetic joint replacements; the American Dental Society states “in general” prophylactic antibiotics are not recommended to prevent prosthetic joint infections. Orthopedic surgeons are concerned with the risk of implant infections following a dental procedure and therefore see high value and low risk in recommending prophylaxis. Patients’ are “stuck in the middle” with conflicting recommendations from OS and dentists. Unnecessary prophylaxis and fear of lawsuits amongst private practice dentists and OS has not been addressed. We review The American Heart Association/American College of Cardiology, American Dental Association, and American Association of Orthopedic Surgeons’ guidelines on dental antibiotic prophylaxis for prevention of endocarditis and prosthetic joint infections. We provide experience on how to engage private practice dentists and OS in dental stewardship using a community-based program.

Doernberg S, Komarow L, Tran T, et al.

AbstractBackgroundPharyngeal and rectal Neisseriagonorrhoeae and Chlamydiatrachomatis play important roles in infection and antibacterial resistance transmission, but no Food and Drug Administration-cleared assays for detection at these sites existed prior to this study. The objective was to estimate performance of assays to detect those infections in pharyngeal and rectal specimens to support regulatory submission.MethodsWe performed a cross-sectional, single-visit study of adults seeking sexually transmitted infection testing at 9 clinics in 7 states. We collected pharyngeal and rectal swabs from participants. The primary outcome was positive and negative percent agreement for detection of N. gonorrhoeae and C. trachomatis for three investigational assays compared to a composite reference. Secondary outcomes included positivity as well as positive and negative predictive values and likelihood ratios. Subgroup analyses included outcomes by symptom status and sex.Results2,598 participants (79% male) underwent testing. We observed N. gonorrhoeae positivity of 8.1% in the pharynx and 7.9% in the rectum and C.trachomatis positivity of 2.0% in the pharynx and 8.7% in the rectum. Positive percent agreement ranged from 84.8% to 96.5% for different anatomic site-infection combinations, while negative percent agreement was 98.8% to 99.6%.ConclusionsThis study utilized a Master Protocol to generate diagnostic performance data for multiple assays from different manufacturers in a single study population, which ultimately supported first-in-class FDA clearance for extragenital assays. We observed very good positive percent agreement when compared to a composite reference method for the detection of both pharyngeal and rectal N. gonorrhoeae and C.trachomatis.RegistrationClinicalTrials.gov number NCT02870101…

Balagopal A, Hwang H, Grudda T, et al.

AbstractHepatitis B virus (HBV) is a leading cause of liver failure and hepatocellular carcinoma worldwide. Approximately 10% of people with HIV also have HBV, and are at higher risk of liver disease progression than in HBV mono-infection. Antivirals, common to HIV and HBV, suppress HBV DNA levels but do not eradicate the virus because the transcriptional template, covalently closed circular DNA (cccDNA), is long-lived in every infected hepatocyte. Using single-cell laser capture microdissection, we isolated >1100 hepatocytes from five HIV/HBV co-infected persons with increasing exposure to HBV antivirals (HB1-5; no exposure to >7 years of exposure), quantifying cccDNA and pre-genomic RNA (pgRNA) in each cell using droplet-digital PCR. The proportion of infected hepatocytes decreased with antiviral exposure from 96.4% (HB1) to 29.8% (HB5). Both the upper cccDNA range and the median pgRNA decreased from HB1 to HB5 (p

N. Susilawathi et al.

Zamora D, Krantz E, Green M, et al.

AbstractBackgroundThe influence of humoral immunity on the prevention of primary cytomegalovirus (CMV) infection after hematopoietic cell transplantation (HCT) is poorly understood.MethodsTo determine whether neutralizing antibodies (nAb) against CMV pentameric complex (PC)-mediated epithelial cell entry decrease CMV infection after HCT, samples were analyzed from a randomized controlled trial conducted by Bowden et al. (1991) of CMV intravenous immunoglobulin (IVIG) prophylaxis. Weekly serum from 61 CMV donor positive / recipient negative (D+/R-) HCT patients (33 control, 28 CMV IVIG) was tested using a PC-entry nAb assay and quantitative CMV polymerase chain reaction (PCR).ResultsThere was a trend toward higher weekly PC-entry nAb titers (p=0.07) and decreased CMV infection by PCR at viral load cutoffs of ≥ 1,000 IU/mL and ≥ 10,000 IU/mL in the CMV IVIG arm. High nAb titers were not significantly protective against CMV infection later after HCT in both study arms. Among CMV-infected patients, each log2 increase in nAb titer was associated with an average 0.2 log10 decrease in concurrent CMV viral load after infection (p=0.001; adjusted for study arm).ConclusionsThis study provides initial support that CMV IVIG prophylaxis moderately enhances PC-entry nAB activity in D+/R- HCT recipients.

Bavinton, Benjamin R.; Rodger, Alison J.

Purpose of review To examine recent literature on the efficacy and effectiveness of HIV treatment in preventing HIV transmission through sexual exposure, at both an individual and at a population level. Recent findings Two recent studies on the individual-level efficacy of treatment as prevention (TasP) have added to the now conclusive evidence that HIV cannot be transmitted sexually when the virus is suppressed. However, four large cluster-randomized population-level trials on universal HIV testing and treatment in Africa have not delivered the expected impact in reducing HIV incidence at a population level. Two of these trials showed no differences in HIV incidence between the intervention and control arms, one demonstrated a nonsignificant lower incidence in the intervention arm, and the fourth trial found a reduction between the communities receiving a combination prevention package and the control arm, but no difference between the immediate treatment plus the prevention package and the control arm. Factors contributing to the disconnect between individual high-level efficacy and population-level effectiveness of TasP include undiagnosed infection, delays in linkage to care, challenges in retention and adherence to antiretroviral therapy (ART), time between ART initiation and viral suppression, and stigma and discrimination. Summary Suppressive ART renders people living with HIV sexually noninfectious. However, epidemic control is unlikely to be achieved by TasP alone. Correspondence to Benjamin R. Bavinton, Kirby Institute, UNSW Sydney, Sydney, NSW 2052, Australia. Tel: +61 2 9385 0990; fax: +61 2 9385 0920; e-mail: bbavinton@kirby.unsw.edu.au Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Ugarte A, Romero Y, Tricas A, et al.

Abstract…