Teaching and Incentives: Substitutes or Complements?

Interventions to promote learning are often categorized into supply- and demand-side approaches. In a randomized experiment to promote learning about COVID-19 among Mozambican adults, we study the interaction between a supply and a demand intervention, respectively: teaching via targeted feedback, and providing financial incentives to learners. In theory, teaching and learner-incentives may be substitutes (crowding out one another) or complements (enhancing one another). Experts surveyed in advance predicted a high degree of substitutability between the two treatments. In contrast, we find substantially more complementarity than experts predicted. Combining teaching and incentive treatments raises COVID-19 knowledge test scores by 0.5 standard deviations, though the standalone teaching treatment is the most cost-effective. The complementarity between teaching and incentives persists in the longer run, over nine months post-treatment.

Correlating cardiac F-18 FDG PET/CT results with intra-operative findings in infectious endocarditis.

BACKGROUND: Multiple studies have demonstrated that when incorporated with conventional imaging modalities, cardiac F-18 PET/CT can aid in diagnosis of endocarditis and improve the sensitivity of the Duke Criteria. These studies used as their gold standard the opinion of an endocarditis team and were characterized by low percentages of patients who underwent surgery. We reviewed 4 years of surgically managed IE cases where F-18 cardiac PET/CT was used to aid diagnosis. METHODS: Between July 2014 and December 2018, we retrospectively reviewed 68 surgically managed endocarditis cases to identify patients who underwent pre-operative PET scans. RESULTS: Fourteen patients were identified who underwent F-18 cardiac PET/CT prior to surgical intervention. Nine cases were classified as possible endocarditis by Duke Criteria and 8 involved prosthetic valves. Twelve out of fourteen scans were interpreted as suggestive of or consistent with endocarditis based on FDG uptake. Twelve positive PETs were associated with either operative findings of infection and/or positive PCR testing on the excised valve. Two patients with negative scans were found to have non-infectious mobile masses intra-operatively, negative valve cultures and negative pathology. CONCLUSION: In a small cohort, F-18 FDG cardiac PET/CT correlated closely with intra-operative findings in patients with endocarditis and helped guide surgical decision-making. It could be considered for addition to the Duke Criteria in the American Heart Association endocarditis guidelines similar to European protocols.

Physician perceptions of a multidisciplinary endocarditis team.

Infectious endocarditis is a highly morbid infection that requires coordination of care across medical and surgical specialties, often through the use of a multidisciplinary team model. Multiple studies have demonstrated that such conferences can improve clinical outcomes. However, little is known about physicians' impressions of these groups. We surveyed 126 (response rate of 30%) internal medicine, infectious diseases, cardiology, and cardiac surgery providers 1 year after the implementation of an endocarditis team at the University of Michigan. Ninety-eight percent of physicians felt that the endocarditis team improved communication between specialties. Additionally, over 85% of respondents agreed that the group influenced diagnostic evaluation, reduced management errors, increased access to surgery, and decreased in-hospital mortality for endocarditis patients. These results suggest that multidisciplinary endocarditis teams are valued by physicians as a tool to improve patient care and serve an important role in increasing communication between providers.

Macrolide-resistant Mycoplasma pneumoniae pneumonia in transplantation: Increasingly typical?

Mycoplasma pneumoniae is one of the most common bacterial causes of pneumonia. Macrolide-resistant M pneumoniae (MRMP) was documented in 7.5% of isolates in the United States. Resistance portends poor outcomes to macrolide therapy, yet patients respond well to fluoroquinolones or tetracyclines such as minocycline. However, MRMP may be under-appreciated because M pneumoniae generally causes relatively mild infections in non-immunosuppressed adults that may resolve without effective therapy and because microbiological confirmation and susceptibility are not routinely performed. We report two cases of pneumonia due to MRMP in kidney transplant recipients. Both patients required hospital admission, worsened on macrolide therapy, and rapidly defervesced on doxycycline or levofloxacin. In one case, M pneumoniae was only identified by multiplex respiratory pathogen panel analysis of BAL fluid. Macrolide resistance was confirmed in both cases by real-time PCR and point mutations associated with macrolide resistance were identified. M pneumoniae was isolated from both cases, and molecular genotyping revealed the same genotype. In conclusion, clinicians should be aware of the potential for macrolide resistance in M pneumoniae, and may consider non-macrolide-based therapy for confirmed or non-responding infections in patients who are immunocompromised or hospitalized.

CD4 is expressed on a heterogeneous subset of hematopoietic progenitors, which persistently harbor CXCR4 and CCR5-tropic HIV proviral genomes in vivo.

Latent HIV infection of long-lived cells is a barrier to viral clearance. Hematopoietic stem and progenitor cells are a heterogeneous population of cells, some of which are long-lived. CXCR4-tropic HIVs infect a broad range of HSPC subtypes, including hematopoietic stem cells, which are multi-potent and long-lived. However, CCR5-tropic HIV infection is limited to more differentiated progenitor cells with life spans that are less well understood. Consistent with emerging data that restricted progenitor cells can be long-lived, we detected persistent HIV in restricted HSPC populations from optimally treated people. Further, genotypic and phenotypic analysis of amplified env alleles from donor samples indicated that both CXCR4- and CCR5-tropic viruses persisted in HSPCs. RNA profiling confirmed expression of HIV receptor RNA in a pattern that was consistent with in vitro and in vivo results. In addition, we characterized a CD4high HSPC sub-population that was preferentially targeted by a variety of CXCR4- and CCR5-tropic HIVs in vitro. Finally, we present strong evidence that HIV proviral genomes of both tropisms can be transmitted to CD4-negative daughter cells of multiple lineages in vivo. In some cases, the transmitted proviral genomes contained signature deletions that inactivated the virus, eliminating the possibility that coincidental infection explains the results. These data support a model in which both stem and non-stem cell progenitors serve as persistent reservoirs for CXCR4- and CCR5-tropic HIV proviral genomes that can be passed to daughter cells.

HIV Preexposure Prophylaxis: A Review.

IMPORTANCE: About 40 000 Americans and 2 million people worldwide are newly infected with HIV each year. The combination antiretroviral regimen, tenofovir disoproxil fumarate (TDF)/emtricitabine, taken as a single pill once daily, has been shown to prevent HIV transmission but is used by fewer than 20% of people who could benefit in the United States. OBSERVATIONS: PubMed was searched on February 15, 2018, using the search terms pre-exposure, prophylaxis, HIV, and PrEP to identify English-language articles published between 2010 and 2018. Four placebo-controlled randomized clinical trials have demonstrated that preexposure prophylaxis (PrEP) with daily dosing of TDF/emtricitabine significantly reduces HIV acquisition in men who have sex with men, high-risk heterosexuals, and injection drug users who share injection equipment. The efficacy of daily TDF/emtricitabine exceeds 90% but is highly correlated with degree of adherence. TDF/emtricitabine is safe and well-tolerated. Only 2% of people discontinue PrEP because of adverse effects. Sexually transmitted infections are common among those using PrEP. Resistance to TDF/emtricitabine when used for PrEP is rare (<0.1%) and usually occurs when PrEP is inadvertently prescribed to individuals with undiagnosed acute HIV infection who have false-negative findings on HIV antibody/antigen testing due to HIV infection acquired within 7 to 10 days of testing. Effective methods are needed to identify individuals at high risk for acquiring HIV, ensure their access to PrEP, and maximize medication adherence. CONCLUSIONS AND RELEVANCE: TDF/emtricitabine is an effective and safe therapy for preventing HIV transmission. Increasing prescription of TDF/emtricitabine for patients at risk of acquiring HIV has the potential to reduce new HIV infections.

CD133+ hematopoietic progenitor cells harbor HIV genomes in a subset of optimally treated people with long-term viral suppression.

BACKGROUND: Hematopoietic progenitor cells (HPCs) in the bone marrow of human immunodeficiency virus (HIV)-infected individuals have been proposed as a persistent reservoir of virus. However, some studies have suggested that HIV genomes detected in HPCs arise from T-cell contamination. METHODS: CD133-sorted HPCs and CD133-depleted bone marrow cells were purified from bone marrow specimens obtained from 11 antiretroviral-treated donors in whom the HIV load had been <48 copies/mL for at least 6 months. CD133 and CD3 expression on the cells was assessed by flow cytometry. HIV DNA was quantified by real-time polymerase chain reaction analysis. RESULTS: HIV genomes were detected in CD133-sorted samples from 6 donors, including 2 in whom viral loads were undetectable for >8 years. CD3(+) T cells represented <1% of cells in all CD133-sorted samples. For 5 of 6 CD133-sorted samples with detectable HIV DNA, the HIV genomes could not be explained by contaminating CD3(+) T cells. Donors with detectable HIV DNA in HPCs received their diagnosis significantly more recently than the remaining donors but had had undetectable viral loads for similar periods. CONCLUSIONS: HIV genomes can be detected in CD133-sorted cells from a subset of donors with long-term viral suppression and, in most cases, cannot be explained by contamination with CD3(+) T cells.

A Biochip with a 3D microfluidic architecture for trapping white blood cells.

We present a microfluidic biochip for trapping single white blood cells (WBCs). The novel biochip, microfabricated using standard surface micromachining processes, consists of an array of precisely engineered microholes that confine single cells in a tight, three dimensional space and mechanically immobilize them. A high (> 87%) trapping efficiency was achieved when WBC-containing samples were delivered to the biochip at the optimal pressure of 3 psi. The biochip can efficiently trap up to 7,500 cells, maintaining a high trapping efficiency even when the number of cells is extremely low (~200 cells). We believe that the developed biochip can be used as a standalone unit in a biology/clinical lab for trapping WBCs as well as other cell types and imaging them using a standard fluorescent microscope at the single cell level. Furthermore, it can be integrated with other miniaturized optical modules to construct a portable platform for counting a wide variety of cells and therefore it can be an excellent tool for monitoring human diseases at the point-of-care.

Virtual Reality Telepresence: 360-Degree Video Streaming with Edge-Compute Assisted Static Foveated Compression.

Real-time communication with immersive 360° video can enable users to be telepresent within a remotely streamed environment. Increasingly, users are shifting to mobile devices and connecting to the Internet via mobile-cellular networks. As the ideal media for 360° videos, some VR headsets now also come with cellular capacity, giving them potential for mobile applications. However, streaming high-quality 360° live video poses challenges for network bandwidth, particularly on cellular connections. To reduce bandwidth requirements, videos can be compressed using viewport-adaptive streaming or foveated rendering techniques. Such approaches require very low latency in order to be effective, which has previously limited their applications on traditional cellular networks. In this work, we demonstrate an end-to-end virtual reality telepresence system that streams ∼6K 360° video over 5G millimeter-wave (mmW) radio. Our use of 5G technologies, in conjunction with mobile edge compute nodes, substantially reduces latency when compared with existing 4G networks, enabling high-efficiency foveated compression over modern cellular networks on par with WiFi. We performed a technical evaluation of our system's visual quality post-compression with peak signal-to-noise ratio (PSNR) and FOVVideoVDP. We also conducted a user study to evaluate users' sensitivity to compressed video. Our findings demonstrate that our system achieves visually indistinguishable video streams while using up to 80% less data when compared with un-foveated video. We demonstrate our video compression system in the context of an immersive, telepresent video calling application.

The Clinical Impact of Implementation of a Multidisciplinary Endocarditis Team.

BACKGROUND: Infectious endocarditis is associated with substantial in-hospital mortality of 15%-20%. Effective management requires coordination between multiple medical and surgical subspecialties, which can often lead to disjointed care. Previous European studies have identified multidisciplinary endocarditis teams as a tool for reducing endocarditis mortality. METHODS: The multidisciplinary endocarditis team was formed in May 2018. The group developed an evidence-based algorithm for management of endocarditis that was used to provide recommendations for hospitalized patients over a 1-year period. Mortality outcomes were then retroactively assessed and compared to a historical control utilizing propensity matching. RESULTS: Between June 2018 and June 2019 the team provided guideline-based recommendations on 56 patients with Duke Criteria-definite endocarditis and at least 1 American Heart Association indication for surgery. The historical control included 68 patients with definite endocarditis and surgical indications admitted between July 1, 2014, and June 30, 2015. In-hospital mortality decreased significantly from 29.4% in 2014-2015 to 7.1% in 2018-2019 (P < .0001). There was a non-significant increase in the rate of surgical intervention after implementation of the team (41.2% vs 55.4%; P = 0.12). Propensity score matching demonstrated similar results. CONCLUSIONS: Implementation of a multidisciplinary endocarditis team was associated with a significant 1-year decrease in all-cause in-hospital mortality for patients with definite endocarditis and surgical indications, in the presence of notable differences between the 2 studied cohorts. In conjunction with previous studies demonstrating their effectiveness, these data support the idea that widespread adoption of endocarditis teams in North America could improve outcomes for this patient population.

Oral human papillomavirus prevalence, persistence, and risk-factors in HIV-positive and HIV-negative adults.

BACKGROUND: HIV has been shown to increase the likelihood of oral HPV infection. In this study, we evaluated the risk of oral HPV in HIV infected patients compared with HIV-negative controls. METHODS: 101 healthy adult volunteers (HIV-) and 245 adults living with HIV infection (HIV+) were recruited from 5 academic medical centers. Questionnaires and saliva samples were obtained every 3-8 months over a period of 2 years (2015-2017). DNA was isolated from the saliva samples and tested for 18 high- and low-risk genotypes. RESULTS: Oral HPV was detected in 23% of HIV + vs. 10% of HIV- participants (p < 0.0001). Men had a higher oral HPV prevalence than women (27% vs. 15% HIV+, p = 0.03, 16% vs. 5% HIV-, p = 0.01). Risk factors among HIV + participants included more lifetime deep kissing and oral sex partners, and history of AIDS. Persistent oral HPV was detected in 23% of HIV + vs. 5% of HIV- participants (p < 0.001). Among 8 HIV + participants with CD4 counts <200 cell/µL none had cleared their HPV infection during the study. CONCLUSIONS: Risk of oral HPV infection and persistence was significantly higher in HIV + adults with a history of poorly controlled HIV, which may put them at increased risk of HPV-associated cancer.

Treatment of endogenous fungal endophthalmitis: focus on new antifungal agents.

Endogenous fungal endophthalmitis, involving only the chorioretinal structures or extending to involve the vitreous (vitritis), is a sight-threatening infection requiring early appropriate therapy. Endophthalmitis is a relatively frequent complication of candidemia and less commonly occurs in patients who have invasive aspergillosis. Because the eye is a protected compartment, penetration of systemically administered antifungal agents is highly variable. In the posterior segment of the eye, amphotericin B (AmB) achieves very poor concentrations, but fluconazole concentrations are high. Among newer antifungal agents, voriconazole shows the most promise, because therapeutic concentrations for most Candida and Aspergillus species are achieved in the vitreous, and its antifungal activity is broad. In contrast, neither posaconazole nor the 3 echinocandins achieve adequate therapeutic concentrations in the vitreous. For sight-threatening macular involvement and vitritis, intravitreal injection of either AmB or voriconazole is helpful to achieve high local antifungal activity as quickly as possible. We review the available evidence regarding the most appropriate use of antifungal agents for endogenous fungal endophthalmitis, with the emphasis on treatment of infections due to Candida species.

A step-by-step guide to implementing a multidisciplinary endocarditis team.

Over the last several years multiple studies, primarily from European centers have demonstrated the clinical and outcomes benefits of multidisciplinary endocarditis teams. Despite this literature, adoption of this approach to patient care has been slower in the United States. While there is literature outlining the optimal composition of an endocarditis team, there is little information to guide providers as they attempt to transform practice from a fragmented, disjointed process to an efficient, collaborative care model. In this review, the authors will outline the steps they took to create and implement a successful multidisciplinary endocarditis team at the University of Michigan. In conjunction with existing data, this piece can be used as a resource for clinicians seeking to improve the care of patients with endocarditis at their institutions.

Factors associated with seroconversion after standard dose hepatitis B vaccination and high-dose revaccination among HIV-infected patients.

BACKGROUND: Patients with HIV-infection often respond poorly to vaccination. We sought to determine rates of seroconversion among HIV-infected patients receiving the hepatitis B vaccine and for non-responders who received high-dose revaccination. METHODS: A single-center retrospective chart review was performed. Patients received either a series of Engerix-B (20 mcg) or Twinrix (standard dose vaccine [SDV]). A subset of non-responders received a higher 40 mcg dose series of Engerix-B (high-dose revaccination [HDR]). RESULTS: 215 patients received SDV with an overall response rate of 46.5%. Among the 115 non-responders, 30 received HDR with an overall response rate of 66.7%. Factors associated with response to SDV included younger age (odds ratio [OR]/1 year=0.97, P=.03), higher CD4 at first dose (OR/100 CD4=1.13, P=.02), and receipt of Twinrix versus Engerix-B (OR=2.3, P=.003). Higher CD4 at first dose was also associated with response to HDR (OR/100 CD4=2.0, P=.02). All factors remained independently associated with response to SDV and HDR on multivariable analysis. CONCLUSIONS: HDR appears to be a viable strategy to achieve seroconversion among HIV-infected patients who fail to respond to SDV. Higher CD4 at vaccination, younger age, and receipt of Twinrix were independently associated with SDV seroconversion.

Clinical Practice Update on Infectious Endocarditis.

Infectious endocarditis is a highly morbid disease with approximately 43,000 cases per year in the United States. The modified Duke Criteria have poor sensitivity; however, advances in diagnostic imaging provide new tools for clinicians to make what can be an elusive diagnosis. There are a number of risk stratification calculators that can help guide providers in medical and surgical management. Patients who inject drugs pose unique challenges for the health care system as their addiction, which is often untreated, can lead to recurrent infections after valve replacement. There is a need to increase access to medication-assisted treatment for opioid use disorders in this population. Recent studies suggest that oral and depo antibiotics may be viable alternatives to conventional intravenous therapy. Additionally, shorter courses of antibiotic therapy are potentially equally efficacious in patients who are surgically managed. Given the complexities involved with their care, patients with endocarditis are best managed by multidisciplinary teams.

Central Nervous System Infection with Histoplasma capsulatum.

Histoplasmosis is an endemic fungal infection that may affect both immune compromised and non-immune compromised individuals. It is now recognized that the geographic range of this organism is larger than previously understood, placing more people at risk. Infection with Histoplasma capsulatum may occur after inhalation of conidia that are aerosolized from the filamentous form of the organism in the environment. Clinical syndromes typically associated with histoplasmosis include acute or chronic pneumonia, chronic cavitary pulmonary infection, or mediastinal fibrosis or lymphadenitis. Disseminated infection can also occur, in which multiple organ systems are affected. In up to 10% of cases, infection of the central nervous system (CNS) with histoplasmosis may occur with or without disseminated infection. In this review, we discuss challenges related to the diagnosis of CNS histoplasmosis and appropriate treatment strategies that can lead to successful outcomes.

Identifying causes of persistent HIV viremia in adult patients at an academic medical center.

OBJECTIVES: Despite many advances in medicine, not all individuals with HIV are able to achieve complete virologic suppression. This retrospective study identifies variables associated with persistent HIV viremia in an academic clinic. METHODS: We studied 66 HIV-infected patients with a viral load of >200 copies/mL over 1 year, with controls matched 1:1 via a propensity score utilizing age at diagnosis, era of diagnosis, gender, and initial CD4 count. We collected data on multiple variables including medications, adherence, comorbidities, hospitalizations, and insurance status. Conditional logistic regression was used for unadjusted and adjusted analyses. RESULTS: A total of 66 viremic cases/matched controls were included. Fewer viremic patients were on antiretroviral therapy for all 12 months (45% vs 77%; odds ratio: 0.33, p = .018) and fewer were of white race (52% vs 70%; odds ratio: 0.49, p = .053). Hospitalization (11% vs 3%; odds ratio: 10, p = .028), underinsurance (20% vs 1%; odds ratio: 5.87, p = .022), and conflicting personal beliefs about their disease (17% vs 3%; odds ratio: 5.5, p = .027) were more common in viremic patients. Psychiatric illness increased the odds of viremia in patients who had four or more visits (odds ratio: 1.63/6.64 with four/five clinic visits, respectively). CONCLUSION: Psychiatric illness is an important contributor to the presence of persistent viremia in HIV-infected patients and deserves further study.