Genomic Answers for Kids: Toward more equitable access to genomic testing for rare diseases in rural populations.

Next-generation sequencing has revolutionized the speed of rare disease (RD) diagnoses. While clinical exome and genome sequencing represent an effective tool for many RD diagnoses, there is room to further improve the diagnostic odyssey of many RD patients. One recognizable intervention lies in increasing equitable access to genomic testing. Rural communities represent a significant portion of underserved and underrepresented individuals facing additional barriers to diagnosis and treatment. Primary care providers (PCPs) at local clinics, though sometimes suspicious of a potential benefit of genetic testing for their patients, have significant constraints in pursuing it themselves and rely on referrals to specialists. Yet, these referrals are typically followed by long waitlists and significant delays in clinical assessment, insurance clearance, testing, and initiation of diagnosis-informed care management. Not only is this process time intensive, but it also often requires multiple visits to urban medical centers for which distance may be a significant barrier to rural families. Therefore, providing early, "direct-to-provider" (DTP) local access to unrestrictive genomic testing is likely to help speed up diagnostic times and access to care for RD patients in rural communities. In a pilot study with a PCP clinic in rural Kansas, we observed a minimum 5.5 months shortening of time to diagnosis through the DTP exome sequencing program as compared to rural patients receiving genetic testing through the "traditional" PCP-referral-to-specialist scheme. We share our experience to encourage future partnerships beyond our center. Our efforts represent just one step in fostering greater diversity and equity in genomic studies.

Insurance denials and diagnostic rates in a pediatric genomic research cohort.

PURPOSE: This study aimed to assess the amount and types of clinical genetic testing denied by insurance and the rate of diagnostic and candidate genetic findings identified through research in patients who faced insurance denials. METHODS: Analysis consisted of review of insurance denials in 801 patients enrolled in a pediatric genomic research repository with either no previous genetic testing or previous negative genetic testing result identified through cross-referencing with insurance prior-authorizations in patient medical records. Patients and denials were also categorized by type of insurance coverage. Diagnostic findings and candidate genetic findings in these groups were determined through review of our internal variant database and patient charts. RESULTS: Of the 801 patients analyzed, 147 had insurance prior-authorization denials on record (18.3%). Exome sequencing and microarray were the most frequently denied genetic tests. Private insurance was significantly more likely to deny testing than public insurance (odds ratio = 2.03 [95% CI = 1.38-2.99] P = .0003). Of the 147 patients with insurance denials, 53.7% had at least 1 diagnostic or candidate finding and 10.9% specifically had a clinically diagnostic finding. Fifty percent of patients with clinically diagnostic results had immediate medical management changes (5.4% of all patients experiencing denials). CONCLUSION: Many patients face a major barrier to genetic testing in the form of lack of insurance coverage. A number of these patients have clinically diagnostic findings with medical management implications that would not have been identified without access to research testing. These findings support re-evaluation of insurance carriers' coverage policies.

Through Their Eyes: Health Care Worker Compliance With Personal Protective Equipment During the COVID-19 Pandemic.

BACKGROUND: Personal protective equipment (PPE) plays a critical role in protecting health care workers (HCWs). During the coronavirus disease-2019 (COVID-19) pandemic, shortages of PPE supplies drastically changed the way PPE was obtained and used by HCWs. PURPOSE: The objective was to investigate the impact of the COVID-19 pandemic and patient isolation type on PPE compliance. METHODS: This investigation was a survey of HCWs at a level 1 trauma teaching hospital regarding PPE compliance patterns prior to and during the COVID-19 pandemic. RESULTS: HCWs reported an increase in PPE compliance during the COVID-19 pandemic. Nearly half (48.6%) of respondents reported that isolation type impacted the decision to wear PPE, of which most were likely to forgo PPE with contact precautions. CONCLUSIONS: HCWs identified multiple barriers to compliance. The underutilization of PPE with contact precautions suggests that the risk of exposure is interpreted as low, and this could be a future target of education.

Reduction of opioid use after implementation of enhanced recovery after bariatric surgery (ERABS).

BACKGROUND: Enhanced recovery after surgery (ERAS) protocols have been extensively proven in lower gastrointestinal surgery to decrease postoperative physiologic stress and length of stay (LOS). ERAS in bariatric surgery (ERABS) varies immensely from each program with inconsistent results with a predominant goal of reducing LOS. Our focus in implementing enhanced recovery after bariatric surgery (ERABS) protocols is aimed at reducing postoperative pain and opioid use. METHODS: This is a retrospective review of patients who underwent laparoscopic Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (VSG) at a single high-volume center from June 2016 to October 2017. Patients on previous standard protocol were categorized into "Pre-Liposomal Bupivacaine (LB) group." After routine use of Exparel™, patients were grouped into "LB group." After ERABS protocol was initiated, patients were categorized into "ERABS/LB group." Postoperative opioids were converted to morphine equivalents units (MEU); pain scores, LOS, and 30-day outcomes were analyzed using combination of t test and Mann-Whitney U. RESULTS: A total of 1340 patients were included in the study: 304 patients in pre-LB group; 754 patients in LB group, and 282 patients in ERABS/LB group. Total hospital opioid use was 58.6 MEU in pre-LB, 40.8 MEU in LB, and 23.8 MEU in ERABS/LB (p = 0.01). ERABS/LB group found a 59.5% decline in MEU requirements compared to pre-LB (p < 0.001) and 44.9% of patients did not require any additional narcotics on the floor compared to 0% in pre-LB group (p < 0.001). ERABS/LB LOS was an average of 1.48 days compared to 1.54 days in pre-LB group (p = 0.03) with an overall decrease of 3.74% in readmission rates (p = 0.03). CONCLUSIONS: Implementation of ERABS significantly reduced postoperative opioid use, LOS, and readmissions. With ERABS, a more profound effect was observed than simply adding Exparel™ to preexisting protocols. Almost half of these patients did not require narcotics while recovering on the surgical floor. More studies are required to assess the true effect of ERABS without use of Exparel™.

Incidence and outcomes of hospital-associated respiratory virus infections by viral species.

BACKGROUND: Although the incidence of hospital-associated respiratory virus infection (HARVI) is well recognized, the risk factors for infection and impact on patient outcomes are not well characterized. METHODS: We identified a cohort of all inpatient admissions ≥24 hours duration at a single academic medical center from 2017 to 2020. HARVI were defined as respiratory virus detected in a test ordered after the 95th percentile of the virus-specific incubation period. Risk factors for HARVI were assessed using Cox proportional hazards models of the competing outcomes of HARVI and discharge. The associations between time-varying HARVI status and the rates of ICU admission, discharge, and in-hospital death were estimated using Cox-proportional hazards models in a competing risk framework. RESULTS: HARVI incidences were 8.8 and 3.0 per 10,000 admission days for pediatric and adult patients, respectively. For adults, congestive heart failure, renal disease, and cancer increased HARVI risk independent of their associations with length of stay. HARVI risk was also elevated for patients admitted in September-June relative to July admissions. For pediatric patients, cardiovascular and respiratory conditions, cancer, medical device dependence, and admission in December increased HARVI risk. Lengths of stay were longer for adults with HARVI compared to those without, and hospital-associated influenza A was associated with increased risk of death. Rates of ICU admission were increased in the 5 days after HARVI identification for adult and pediatric patients. HARVI was not associated with length of stay or death among pediatric patients. CONCLUSIONS: HARVI is associated chronic health conditions and increases morbidity and mortality.

Large-event medicine--event characteristics impacting medical need.

Large events have been defined in many ways, from the vague description of a focused gathering of people to the more specific description of an event with at least 1,000 spectators and participants who are gathered at a specific location for a defined period of time. Regardless of the definition applied, the actual medical requirements vary considerably from one event to the next. The ability to predict these medical needs allows for the provision of adequate medical support. Many factors contribute to medical need at a large event, including event type, weather (particularly heat index), the presence of alcohol and / or illicit drugs, the number of participants, event duration, crowd demographics, and venue characteristics. This review will focus on the various features of large events such that the medical planner can better understand the challenge and provide adequate resource for patient care.

Contrasting in vitro and in vivo methanol oxidation activities of lanthanide-dependent alcohol dehydrogenases XoxF1 and ExaF from Methylobacterium extorquens AM1.

Lanthanide (Ln) elements are utilized as cofactors for catalysis by XoxF-type methanol dehydrogenases (MDHs). A primary assumption is that XoxF enzymes produce formate from methanol oxidation, which could impact organisms that require formaldehyde for assimilation. We report genetic and phenotypic evidence showing that XoxF1 (MexAM1_1740) from Methylobacterium extorquens AM1 produces formaldehyde, and not formate, during growth with methanol. Enzyme purified with lanthanum or neodymium oxidizes formaldehyde. However, formaldehyde oxidation via 2,6-dichlorophenol-indophenol (DCPIP) reduction is not detected in cell-free extracts from wild-type strain methanol- and lanthanum-grown cultures. Formaldehyde activating enzyme (Fae) is required for Ln methylotrophic growth, demonstrating that XoxF1-mediated production of formaldehyde is essential. Addition of exogenous lanthanum increases growth rate with methanol by 9-12% but does not correlate with changes to methanol consumption or formaldehyde accumulation. Transcriptomics analysis of lanthanum methanol growth shows upregulation of xox1 and downregulation of mxa genes, consistent with the Ln-switch, no differential expression of formaldehyde conversion genes, downregulation of pyrroloquinoline quinone (PQQ) biosynthesis genes, and upregulation of fdh4 formate dehydrogenase (FDH) genes. Additionally, the Ln-dependent ethanol dehydrogenase ExaF reduces methanol sensitivity in the fae mutant strain when lanthanides are present, providing evidence for the capacity of an auxiliary role for ExaF during Ln-dependent methylotrophy.