PurposePhysicians increasingly receive genomic test results they did not order, which we term “unsolicited genomic results” (UGRs). We asked physicians how they think such results will affect them and their patients.MethodsSemi-structured interviews were conducted with adult and pediatric primary care and subspecialty physicians at four sites affiliated with a large-scale return-of-results project led by the Electronic Medical Records and Genomics (eMERGE) Network. Twenty-five physicians addressed UGRs and: 1) perceived need for actionability, 2) impact on patients, 3) health care workflow, 4) return of results process, and 5) responsibility for results.ResultsPhysicians prioritize actionability of UGRs and the need for clear, evidence-based “paths” for action coupled with clinical decision support (CDS). They identified potential harms to patients including anxiety, false reassurance, and clinical disutility. Clinicians worried about anticipated workflow issues including responding to UGRs and unreimbursed time. They disagreed about who was responsible for responding to UGRs.ConclusionThe prospect of receiving UGRs for otherwise healthy patients raises important concerns for physicians. Their responses informed development of an in-depth survey for physicians following return of UGRs. Strategic workflow integration of UGRs will likely be necessary to empower physicians to serve their patients effectively.

B alamuthia mandrillaris is an ameba that can cause skin lesions, endophthalmitis, or granulomatous amebic encephalitis (GAE) in previously healthy patients. Routes of infection include possible soil exposure (1) and transplanted organs from infected donors (2,3). The mortality rate is high. During 1974-2016, of 109 Balamuthia GAE cases in the United States, 10 patients survived; mortality rate was >90% (4).The recommended medication regimen for Balamuthia GAE includes pentamidine, sulfadiazine, azithromycin/clarithromycin, fluconazole, flucytosine, and miltefosine (5). This regimen is based on survivor case series, and results have been inconsistent. Of those medications, only miltefosine, pentamidine, and azithromycin exhibit in vitro evidence of amebicidal or amebistatic activity (6,7). Furthermore, in vitro activity requires high concentrations of drug that are implausible in vivo (50% inhibitory concentration for azithromycin 244 μM and miltefosine 62 μM) (6). We report a patient with B. mandrillaris granulomatous amebic encephalitis who survived after receiving treatment with nitroxoline, a drug typically used to treat urinary tract infections, which was identified in a screen for drugs with amebicidal activity against Balamuthia. The CaseThe patient was a man in his 50s, with no remarkable medical history, who received care at a hospital in northern California, USA, after experiencing a generalized seizure. Magnetic resonance imaging (MRI) demonstrated a solitary left temporal lobe T2 hyperintensity with gadolinium rim enhancement and surrounding edema. After receiving treatment with dexamethasone and levetiracetam, he was transferred to the University of California San Francisco Medical Center (UCSF) (Figure 1).Examination by neurology consultants indicated disorientation, inattention, moderate aphasia, and mild right hemiparesis. The aphasia and hemiparesis improved during hospitalization, suggesting that those signs were postictal. Cerebrospinal fluid (CSF) testing revealed increased nucleated cells up to 80/ UL (60% lymphocytes, 17% neutrophils, 23% monocytes), protein concentration 38 mg/dL, and glucose concentration 100 mg/dL. A biopsy sample from the left temporal lobe lesion was preliminarily reported as well-formed granulomata with acute inflammation (Figure 2, panel A).Cultures from the brain biopsy sample did not grow bacteria, fungi, or mycobacteria. We performed metagenomic next-generation sequencing (mNGS) on a CSF sample (8,9) and sent brain biopsy samples for universal broad-range PCR amplicon sequencing (uPCR) for bacteria, fungi, Mycobacterium tuberculosis,

Objectives The study aimed to understand potential barriers to the adoption of health information technology projects that are released as free and open source software (FOSS). Methods We conducted a survey of research consortia participants engaged in genomic medicine implementation to assess perceived institutional barriers to the adoption of three systems: ClinGen electronic health record (EHR) Toolkit, DocUBuild, and MyResults.org. The survey included eight barriers from the Consolidated Framework for Implementation Research (CFIR), with additional barriers identified from a qualitative analysis of open-ended responses. Results We analyzed responses from 24 research consortia participants from 18 institutions. In total, 14 categories of perceived barriers were evaluated, which were consistent with other observed barriers to FOSS adoption. The most frequent perceived barriers included lack of adaptability of the system, lack of institutional priority to implement, lack of trialability, lack of advantage of alternative systems, and complexity. Conclusion In addition to understanding potential barriers, we recommend some strategies to address them (where possible), including considerations for genomic medicine. Overall, FOSS developers need to ensure systems are easy to trial and implement and need to clearly articulate benefits of their systems, especially when alternatives exist. Institutional champions will remain a critical component to prioritizing genomic medicine projects.

This case report describes a survivor of Balamuthia mandrillaris granulomatous amoebic encephalitis (GAE) after treatment with the novel agent nitroxoline, a drug typically used to treat urinary tract infections. Nitroxoline was previously identified in a screen of US and European approved drugs for amoebicidal activity against this pathogen. We describe its successful first use in treating this rare and deadly disease.

No abstract