Key Points Question Do practitioners understand the probability of common clinical diagnoses? Findings In this survey study of 553 practitioners performing primary care, respondents overestimated the probability of diagnosis before and after testing. This posttest overestimation was associated with consistent overestimates of pretest probability and overestimates of disease after specific diagnostic test results. Meaning These findings suggest that many practitioners are unaccustomed to using probability in diagnosis and clinical practice. Widespread overestimates of the probability of disease likely contribute to overdiagnosis and overuse.

We examined contamination of healthcare worker (HCW) gown and gloves after caring for patients with Klebsiella Producing Carbapenemase-producing and non-KPC-producing Klebsiella as a proxy for horizontal transmission. Contamination rate with Klebsiella is similar to MRSA and VRE, with 14% (31/220) of HCW-patient interactions resulting in contamination of gloves and gowns.

Following a bite from an infected tick, tick-borne flaviviruses cause encephalitis, meningitis and hemorrhagic fever in humans. Although these viruses spend most of their time in the tick, little is known regarding the virus-vector interactions. We developed a simple method for synchronously infecting Ixodes scapularis larvae with Langat virus (LGTV) by immersion in media containing the virus. This technique resulted in approximately 96% of ticks becoming infected. LGTV infection and replication were demonstrated by both viral antigen expression and the accumulation of viral RNA. Furthermore, ticks transmitted LGTV to 100% of the mice and maintained the virus through molting into the next life stage. This technique circumvents limitations present in the current methods by mimicking the natural route of infection and by using attenuated virus strains to infect ticks, thereby making this technique a powerful tool to study both virus and tick determinants of replication, pathogenesis and transmission.

Narrative abstract CDC risk adjustment methods for CLABSI only adjust for ICU type. This cohort study explored risk factors for CLABSI using two comorbidity classification schemes, the Charlson Comorbidity Index and the Chronic Disease Score. Our study supports the need for additional research into risk factors for CLABSI, including electronically-available comorbid conditions.

Tick-borne flaviviruses are maintained in nature in an enzootic cycle involving a tick vector and a vertebrate host. Thus, the virus replicates in two disparate hosts, each providing selective pressures that can influence virus replication and pathogenicity. To identify viral determinants associated with replication in the individual hosts, plaque purified Langat virus (TP21pp) was adapted to growth in mouse or tick cell lines to generate two virus variants, MNBp20 and ISEp20, respectively. Virus adaptation to mouse cells resulted in four amino acid changes in MNBp20 relative to TP21pp, occurring in E, NS4A and NS4B. A comparison between TP21pp and ISEp20 revealed three amino acid modifications in M, NS3 and NS4A of ISEp20. ISEp20, but not MNBp20, was attenuated following intraperitoneal inoculation of mice. Following isolation from mice brains, additional mutations reproducibly emerged in E and NS3 of ISEp20 that were possibly compensatory for the initial adaptation to tick cells. Thus, our data implicate a role for E, M, NS3, NS4A and NS4B in host adaptation and pathogenicity of tick-borne flaviviruses.

Background - Familial hypercholesterolemia (FH) is the most common cardiovascular genetic disorder and, if left untreated, is associated with increased risk of premature atherosclerotic cardiovascular disease, the leading cause of preventable death in the United States. Although FH is common, fatal, and treatable, it is underdiagnosed and undertreated due to a lack of systematic methods to identify individuals with FH and limited uptake of cascade testing. Methods and Results - This mixed-method, multi-stage study will optimize, test, and implement innovative approaches for both FH identification and cascade testing in three aims. To improve identification of individuals with FH, in Aim 1 we will compare and refine automated phenotype-based and genomic approaches to identify individuals likely to have FH. To improve cascade testing uptake for at-risk individuals, in Aim 2 we will use a patient-centered design thinking process to optimize and develop novel, active family communication methods. Using a prospective, observational pragmatic trial we will assess uptake and effectiveness of each family communication method on cascade testing. Guided by an implementation science framework, in Aim 3 we will develop a comprehensive guide to identify individuals with FH. Using the Conceptual Model for Implementation Research, we will evaluate implementation outcomes including feasibility, acceptability, and perceived sustainability as well as health outcomes related to the optimized methods and tools developed in Aims 1 and 2. Conclusions - Data generated from this study will address barriers and gaps in care related to underdiagnosis of FH by developing and optimizing tools to improve FH identification and cascade testing.

Background Guidelines in sub-Saharan Africa on when HIV-seronegative persons should re-test range from never to annually for lower-risk populations and from annually to every 3 months for high risk populations. Methods We designed a mathematical model to investigate the most cost-effective frequency with which an HIV-seronegative tester should re-test for HIV. Cost of HIV counseling and testing (HCT), linkage to care, treatment costs, disease progression and mortality, and HIV transmission are modeled for three hypothetical cohorts with annual HIV incidence of 0.8%, 1.3%, and 4.0%, respectively. The model compares costs, quality-adjusted life-years gained, and secondary infections averted from testing intervals ranging from 3 months to 30 years. Input parameters from sub-Saharan Africa were used and explored in sensitivity analyses. Results Accounting for secondary infections averted, the most cost-effective testing frequency was every 7.5 years for 0.8% incidence ($701 per quality-adjusted life year (QALY) gained), every 5 years for 1.3% incidence ($681/QALY), and every two years for 4.0% incidence ($635/QALY). Most testing strategies implied a cost per QALY gained at or below the average GDP per capita in sub-Saharan Africa ($2,031/QALY). Optimal testing strategies and their relative cost effectiveness were most sensitive to assumptions about HCT and treatment costs, rates of CD4 decline, and rates of HIV transmission. Conclusions Regular re-testing for HIV may be cost-effective for both high- and low-risk populations in sub-Saharan Africa. The most cost-effective testing frequency varies with HIV incidence. Our data demonstrate benefits of tailoring testing intervals to resource constraints and local HIV incidence rates.

Assessment of children’s learning and performance in low and middle income countries has been critiqued as lacking a gold standard, an appropriate norm reference group, and demonstrated applicability of assessment tasks to the context. This study was designed to examine the performance of three nonverbal and one adapted verbal measure of children’s problem solving, memory, motivation, and attention across five culturally diverse sites. The goal was to evaluate the tests as indicators of individual differences affected by life events and care circumstances for vulnerable children. We conclude that the measures can be successfully employed with fidelity in non-standard settings in LMICs, and are associated with child age and educational experience across the settings. The tests can be useful in evaluating variability in vulnerable child outcomes.