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Diagnostic tests can detect diseases, monitor responses, and inform treatments. They are vital to the effective management of disease. There have been significant advances in the engineering of new diagnostic technologies. These technologies may forgo sample extraction, simplify readout, or automate processing. Many researchers design these diagnostics based on test performance in a limited sample subset. This approach ignores the intertwined relationship between patient characteristics and diagnostic test results. Yet, it is important to understand the clinical decision‐making workflow and how the disease manifests in order to optimally design diagnostic tests. This review article explores the three aspects of incorporating patient characteristics to maximize diagnostic performance. 1) Characterize patient populations using patient demographics, disease prevalence, and other unique features. 2) Use the characteristics of the patient population to establish design requirements. 3) Determine the best use case since each case has different performance and target requirements. In this framework the clinical, technological, and unmet needs of a patient population shape the diagnostics design requirements. Following these steps will lead to maximal diagnostic performance and poise new diagnostics for real world use. [ABSTRACT FROM AUTHOR]

COVID‐19 has halted research around the globe and forced researchers out of their laboratories. Non‐emergency medical appointments were canceled. Ongoing clinical trials were challenged to create new modes of operation while public pressure mounted to find therapeutic options against COVID‐19. Yet, the inability to conduct research during COVID‐19 was overcome with cooperation, resource sharing, and compassion, which provides important lessons on how to improve health related research as we enter a new normal. [ABSTRACT FROM AUTHOR]

Introduction: The significance of granuloma in explanted lungs of lung transplant recipients (LTR) on the development of post‐transplant mycobacterial infection is unclear. Methods: A retrospective review comparing LTRs and heart‐lung transplant (H‐LTR) recipients with granuloma in the explanted lungs between 2000 and 2012 (excluding those LTRs with granuloma due to sarcoidosis) and LTRs or H‐LTRs without granuloma. Patients were followed for 2 years post‐transplant. Results: A total of 144 LTRs and 4 H‐LTRs with granulomas (75 necrotizing and 73 non‐necrotizing) and a comparator cohort of 144 LTRs and 4 H‐LTRs without granuloma were analyzed. In LTRs with granulomas, identification of infectious organisms was more common by histopathology (35 AFB and 22 fungal) compared to cultures (six NTM and seven fungal) taken around time of the transplant. LTRs with granulomas were more likely to have pre‐transplant non‐tuberculous mycobacteria (NTM) infection compared to LTRs without granuloma; P <.01. In the multivariate analysis, having granuloma or positive mycobacterial cultures at time of transplant were associated with increased risk of post‐transplant mycobacterial infection (HR = 1.8 95% CI [1.024‐3.154]; P =.041 and HR = 2.083 95% CI [1.011‐4.292]; P =.047). Although there was a trend toward increase mycobacterial disease in those with granulomas P =.056, there was no difference in survival post‐transplantation between those with or without granuloma in the explanted lung; P =.886. Conclusion: The presence of granuloma in the explanted lungs of LTRs or positive mycobacterial cultures at time of transplant is associated with an increased risk of mycobacterial infection post‐transplant. [ABSTRACT FROM AUTHOR]

To date there are no approved antiviral drugs for the treatment of Ebola virus disease (EVD). While a number of candidate drugs have shown limited efficacy in vitro and/or in non-human primate studies, differences in experimental methodologies make it difficult to compare their therapeutic effectiveness. Using an in vitro model of Ebola Zaire replication with transcription-competent virus like particles (trVLPs), requiring only level 2 biosafety containment, we compared the activities of the type I interferons (IFNs) IFN-α and IFN-ß, a panel of viral polymerase inhibitors (lamivudine (3TC), zidovudine (AZT) tenofovir (TFV), favipiravir (FPV), the active metabolite of brincidofovir, cidofovir (CDF)), and the estrogen receptor modulator, toremifene (TOR), in inhibiting viral replication in dose-response and time course studies. We also tested 28 two- and 56 three-drug combinations against Ebola replication. IFN-α and IFN-ß inhibited viral replication 24 hours post-infection (IC50 0.038μM and 0.016μM, respectively). 3TC, AZT and TFV inhibited Ebola replication when used alone (50–62%) or in combination (87%). They exhibited lower IC50 (0.98–6.2μM) compared with FPV (36.8μM), when administered 24 hours post-infection. Unexpectedly, CDF had a narrow therapeutic window (6.25–25μM). When dosed >50μM, CDF treatment enhanced viral infection. IFN-ß exhibited strong synergy with 3TC (97.3% inhibition) or in triple combination with 3TC and AZT (95.8% inhibition). This study demonstrates that IFNs and viral polymerase inhibitors may have utility in EVD. We identified several 2 and 3 drug combinations with strong anti-Ebola activity, confirmed in studies using fully infectious ZEBOV, providing a rationale for testing combination therapies in animal models of lethal Ebola challenge. These studies open up new possibilities for novel therapeutic options, in particular combination therapies, which could prevent and treat Ebola infection and potentially reduce drug resistance. [ABSTRACT FROM AUTHOR]