Utility of targeted gene sequencing to differentiate myeloid malignancies from other cytopenic conditions.

The National Heart, Lung, and Blood Institute-funded National MDS Natural History Study (NCT02775383) is a prospective cohort study enrolling patients with cytopenia with suspected myelodysplastic syndromes (MDS) to evaluate factors associated with disease. Here, we sequenced 53 genes in bone marrow samples harvested from 1298 patients diagnosed with myeloid malignancy, including MDS and non-MDS myeloid malignancy or alternative marrow conditions with cytopenia based on concordance between independent histopathologic reviews (local, centralized, and tertiary to adjudicate disagreements when needed). We developed a novel 2-stage diagnostic classifier based on mutational profiles in 18 of 53 sequenced genes that were sufficient to best predict a diagnosis of myeloid malignancy and among those with a predicted myeloid malignancy, predict whether they had MDS. The classifier achieved a positive predictive value (PPV) of 0.84 and negative predictive value (NPV) of 0.8 with an area under the receiver operating characteristic curve (AUROC) of 0.85 when classifying patients as having myeloid vs no myeloid malignancy based on variant allele frequencies (VAFs) in 17 genes and a PPV of 0.71 and NPV of 0.64 with an AUROC of 0.73 when classifying patients as having MDS vs non-MDS malignancy based on VAFs in 10 genes. We next assessed how this approach could complement histopathology to improve diagnostic accuracy. For 99 of 139 (71%) patients (PPV of 0.83 and NPV of 0.65) with local and centralized histopathologic disagreement in myeloid vs no myeloid malignancy, the classifier-predicted diagnosis agreed with the tertiary pathology review (considered the internal gold standard).

Reasons for unsuccessful research submissions to JAAPA.

OBJECTIVE: PA authors face many barriers to publication and may benefit from additional transparency in the editorial decision-making process. This study examined the most common reasons for rejection of original research submissions to JAAPA. METHODS: Senior JAAPA editors conducted a thematic analysis of reviewer and editor comments and used these broad themes to classify the reasons for rejection of original research manuscripts submitted to JAAPA. RESULTS: From October 2015 through December 2018, 77 research manuscripts were submitted to JAAPA. Fifty-six manuscripts were rejected, resulting in an overall rejection rate of 73.7%. Common reasons for rejection included: methodologic issues (55.4%), content outside the journal's scope (42.9%), poor writing quality (17.9%), guideline nonadherence (3.6%), lack of novelty (3.6%), and author(s) declining to revise the manuscript (1.8%). CONCLUSION: The most common reasons for manuscript rejection can be overcome through research planning and manuscript preparation.

Finding Success in Scholarship: How Physician Assistant Educators Can Overcome Barriers to Publication.

ABSTRACT: Publishing scholarly work offers several benefits for physician assistants (PAs) in faculty roles. It allows them to establish expertise, disseminate knowledge, and advance their careers. However, due to a variety of barriers, PAs are often unable to build a portfolio of scholarly articles. They frequently lack the time, training, experience, and resources to complete large academic projects and navigate the complex publication process. This article offers 6 key strategies to help PAs in academic settings pursue scholarly work and achieve publication.

Reasons PAs leave their jobs.

PURPOSE: Employee turnover is an important indicator that carries a heavy financial cost for healthcare organizations. Although previous research has highlighted some factors associated with turnover, the reasons physician assistants (PAs) leave their jobs are not fully understood. This study aimed to determine the most common reasons behind PA turnover. METHODS: In 2019, the American Academy of PAs (AAPA) distributed a survey to all PAs with an eligible email address. The survey included a question asking respondents if they had left or changed their job in the past year. Respondents answering this question in the affirmative were asked a follow-up multiple-choice question to determine the reason behind this change. RESULTS: A total of 13,088 PAs responded to the AAPA salary survey; of these, 1,261 reported leaving a job within the past year. The most common reasons provided for leaving a job were: better work/life balance (n = 209, 16.8%), moved (n = 208, 16.7%), better management/leadership/environment (reasons related to toxic/abusive environment) (n = 170, 13.6%), and better compensation/benefits (n = 148, 11.9%). CONCLUSION: Employers should focus on common reasons for turnover that can be reasonably addressed. Of the top three reasons behind PA turnover, those related to toxic/abusive work environments may be the most practical and important to address.

Validation of publicly-available software used in analyzing NGS data for HIV-1 drug resistance mutations and transmission networks in a Washington, DC, Cohort.

The DC Cohort is an ongoing longitudinal observational study of persons living with HIV. To better understand HIV-1 drug resistance and potential transmission clusters among these participants, we performed targeted, paired-end next-generation sequencing (NGS) of protease, reverse transcriptase and integrase amplicons. We elected to use free, publicly-available software (HyDRA Web, Stanford HIVdb and HIV-TRACE) for data analyses so that laboratory personnel without extensive bioinformatics expertise could use it; making the approach accessible and affordable for labs worldwide. With more laboratories transitioning away from Sanger-based chemistries to NGS platforms, lower frequency drug resistance mutations (DRMs) can be detected, yet their clinical relevance is uncertain. We looked at the impact choice in cutoff percentage had on number of DRMs detected and found an inverse correlation between the two. Longitudinal studies will be needed to determine whether low frequency DRMs are an early indicator of emerging resistance. We successfully validated this pipeline against a commercial pipeline, and another free, publicly-available pipeline. RT DRM results from HyDRA Web were compared to both SmartGene and PASeq Web; using the Mantel test, R2 values were 0.9332 (p<0.0001) and 0.9097 (p<0.0001), respectively. PR and IN DRM results from HyDRA Web were then compared with PASeq Web only; using the Mantel test, R2 values were 0.9993 (p<0.0001) and 0.9765 (p<0.0001), respectively. Drug resistance was highest for the NRTI drug class and lowest for the PI drug class in this cohort. RT DRM interpretation reports from this pipeline were also highly correlative compared to SmartGene pipeline; using the Spearman's Correlation, rs value was 0.97757 (p<0.0001). HIV-TRACE was used to identify potential transmission clusters to better understand potential linkages among an urban cohort of persons living with HIV; more individuals were male, of black race, with an HIV risk factor of either MSM or High-risk Heterosexual. Common DRMs existed among individuals within a cluster. In summary, we validated a comprehensive, easy-to-use and affordable NGS approach for tracking HIV-1 drug resistance and identifying potential transmission clusters within the community.