Intermountain Medical Center

Importance: Therapy for advanced melanoma has transformed during the past decade, but early detection and prognostic assessment of cutaneous melanoma (CM) remain paramount goals. Best practices for screening and use of pigmented lesion evaluation tools and gene expression profile (GEP) testing in CM remain to be defined. Objective: To provide consensus recommendations on optimal screening practices and prebiopsy diagnostic, postbiopsy diagnostic, and prognostic assessment of CM. Evidence review: Case scenarios were interrogated using a modified Delphi consensus method. Melanoma panelists (n = 60) were invited to vote on hypothetical scenarios via an emailed survey (n = 42), which was followed by a consensus conference (n = 51) that reviewed the literature and the rationale for survey answers. Panelists participated in a follow-up survey for final recommendations on the scenarios (n = 45). Findings: The panelists reached consensus (≥70% agreement) in supporting a risk-stratified approach to melanoma screening in clinical settings and public screening events, screening personnel recommendations (self/partner, primary care provider, general dermatologist, and pigmented lesion expert), screening intervals, and acceptable appointment wait times. Participants also reached consensus that visual and dermoscopic examination are sufficient for evaluation and follow-up of melanocytic skin lesions deemed innocuous. The panelists reached consensus on interpreting reflectance confocal microscopy and some but not all results from epidermal tape stripping, but they did not reach consensus on use of certain pigmented lesion evaluation tools, such as electrical impedance spectroscopy. Regarding GEP scores, the panelists reached consensus that a low-risk prognostic GEP score should not outweigh concerning histologic features when selecting patients to undergo sentinel lymph node biopsy but did not reach consensus on imaging recommendations in the setting of a high-risk prognostic GEP score and low-risk histology and/or negative nodal status. Conclusions and relevance: For this consensus statement, panelists reached consensus on aspects of a risk-stratified approach to melanoma screening and follow-up as well as use of visual examination and dermoscopy. These findings support a practical approach to diagnosing and evaluating CM. Panelists did not reach consensus on a clearly defined role for GEP testing in clinical decision-making, citing the need for additional studies to establish the clinical use of existing GEP assays.

Background: SARS-CoV-2 genomic and subgenomic RNA levels are frequently used as a correlate of infectiousness. The impact of host factors and SARS-CoV-2 lineage on RNA viral load is unclear. Methods: Total nucleocapsid (N) and subgenomic N (sgN) RNA levels were measured by RT-qPCR in specimens from 3,204 individuals hospitalized with COVID-19 at 21 hospitals. RT-qPCR cycle threshold (Ct) values were used to estimate RNA viral load. The impact of time of sampling, SARS-CoV-2 variant, age, comorbidities, vaccination, and immune status on N and sgN Ct values were evaluated using multiple linear regression. Results: Ct values at presentation for N (mean ±standard deviation) were 24.14±4.53 for non-variants of concern, 25.15±4.33 for Alpha, 25.31±4.50 for Delta, and 26.26±4.42 for Omicron. N and sgN RNA levels varied with time since symptom onset and infecting variant but not with age, comorbidity, immune status, or vaccination. When normalized to total N RNA, sgN levels were similar across all variants. Conclusions: RNA viral loads were similar among hospitalized adults, irrespective of infecting variant and known risk factors for severe COVID-19. Total N and subgenomic RNA N viral loads were highly correlated, suggesting that subgenomic RNA measurements adds little information for the purposes of estimating infectivity.

Background: The left ventricular hemodynamic load differs between aortic regurgitation (AR) and primary mitral regurgitation (MR). We used cardiac magnetic resonance to compare left ventricular remodeling patterns, systemic forward stroke volume, and tissue characteristics between patients with isolated AR and isolated MR. Methods: We assessed remodeling parameters across the spectrum of regurgitant volume. Left ventricular volumes and mass were compared against normal values for age and sex. We calculated forward stroke volume (planimetered left ventricular stroke volume-regurgitant volume) and derived a cardiac magnetic resonance-based systemic cardiac index. We assessed symptom status according to remodeling patterns. We also evaluated the prevalence of myocardial scarring using late gadolinium enhancement imaging, and the extent of interstitial expansion via extracellular volume fraction. Results: We studied 664 patients (240 AR, 424 primary MR), median age of 60.7 (49.5-69.9) years. AR led to more pronounced increases in ventricular volume and mass compared with MR across the spectrum of regurgitant volume (P<0.001). In ≥moderate regurgitation, AR patients had a higher prevalence of eccentric hypertrophy (58.3% versus 17.5% in MR; P<0.001), whereas MR patients had normal geometry (56.7%) followed by myocardial thinning with low mass/volume ratio (18.4%). The patterns of eccentric hypertrophy and myocardial thinning were more common in symptomatic AR and MR patients (P<0.001). Systemic cardiac index remained unchanged across the spectrum of AR, whereas it progressively declined with increasing MR volume. Patients with MR had a higher prevalence of myocardial scarring and higher extracellular volume with increasing regurgitant volume (P value for trend <0.001), whereas they were unchanged across the spectrum of AR (P=0.24 and 0.42, respectively). Conclusions: Cardiac magnetic resonance identified significant heterogeneity in remodeling patterns and tissue characteristics at matched degrees of AR and MR. Further research is needed to examine if these differences impact reverse remodeling and clinical outcomes after intervention.

Objectives: Confidentiality is imperative when caring for adolescents, yet the 21st Century Cures Act ensures guardian access to some of their child's documentation. Pediatric Hospital Medicine (PHM) history and physical (H&P) notes are visible to guardians, whereas adolescent sensitive notes (ASN) are not. Our aim was to decrease sexual history and substance use (SHSU) documentation in H&P notes. Methods: This quality improvement study included adolescents ages 13 to 17 from August 1, 2020 to May 31, 2021. Interventions included disappearing help text added to PHM H&P template prompting placement of positive SHSU in the ASN, editing of disappearing help text to encourage copy and paste of all SHSU into ASN, and communication to providers. The primary outcome measure was documentation of SHSU in H&P notes. The process measure was presence of ASNs. The balancing measures were documentation of unapproved social history domains in the ASN and encounters with no SHSU documentation. Statistical process control was used for analysis. Results: Four hundred fifty patients were included in this analysis. There was decreased documentation of SHSU within H&P notes from means of 58.4% and 50.4% to 8.4% and 11.4%, respectively. There was increased utilization of ASN from 22.8% to 72.3%. Special cause variation occurred. Other unapproved domains in the ASN decreased. Encounters with no SHSU were unchanged. Conclusions: The quality improvement intervention of disappearing help text in PHM H&Ps was associated with decreased documentation of SHSU within H&P notes and increased utilization of ASN. This simple intervention helps maintain confidentiality. Further interventions may include utilization of disappearing help text in other specialties.

Early in the COVID-19 pandemic, no effective treatment existed to prevent clinical worsening of COVID-19 among recently diagnosed outpatients. At the University of Utah, Salt Lake City, Utah, we conducted a phase 2 prospective parallel group randomized placebo-controlled trial (NCT04342169) to determine whether hydroxychloroquine given early in disease reduces the duration of SARS-CoV-2 shedding. We enrolled nonhospitalized adults (≥18 years of age) with a recent positive diagnostic test for SARS-CoV-2 (within 72 h of enrollment) and adult household contacts. Participants received either 400 mg hydroxychloroquine by mouth twice daily on day 1 followed by 200 mg by mouth twice daily on days 2 to 5 or oral placebo with the same schedule. We performed SARS-CoV-2 nucleic acid amplification testing (NAAT) on oropharyngeal swabs on days 1 to 14 and 28 and monitored clinical symptomatology, rates of hospitalization, and viral acquisition by adult household contacts. We identified no overall differences in the duration of oropharyngeal carriage of SARS-CoV-2 (hazard ratio of viral shedding time comparing hydroxychloroquine to placebo, 1.21; 95% confidence interval [CI], 0.91, 1.62). Overall, 28-day hospitalization incidence was similar between treatments (4.6% hydroxychloroquine versus 2.7% placebo). No differences were seen in symptom duration, severity, or viral acquisition in household contacts between treatment groups. The study did not reach the prespecified enrollment target, which was likely influenced by a steep decline in COVID-19 incidence corresponding to the initial vaccine rollout in the spring of 2021. Oropharyngeal swabs were self-collected, which may introduce variability in these results. Placebo treatments were not identical to hydroxychloroquine treatments (capsules versus tablets) which may have led to inadvertent participant unblinding. In this group of community adults early in the COVID-19 pandemic, hydroxychloroquine did not significantly alter the natural history of early COVID-19 disease. (This study has been registered at ClinicalTrials.gov under registration no. NCT04342169). IMPORTANCE Early in the COVID-19 pandemic, no effective treatment existed to prevent clinical worsening of COVID-19 among recently diagnosed outpatients. Hydroxychloroquine received attention as a possible early treatment; however, quality prospective studies were lacking. We conducted a clinical trial to test the ability of hydroxychloroquine to prevent clinical worsening of COVID-19.

Objective: Our study aimed to elucidate the presence, antigen specificities, and potential clinical association of anti-neutrophil extracellular trap (anti-NET) antibodies in a multinational cohort of antiphospholipid antibody (aPL)-positive patients who did not have lupus. Methods: Anti-NET IgG/IgM were measured in sera of 389 aPL-positive patients; 308 met the classification criteria for APS. Multivariate logistic regression with best variable model selection was used to determine clinical associations. For a subset of the patients (n=214), we profiled autoantibodies with an autoantigen microarray platform. Results: We found elevated levels of anti-NET IgG and/or IgM in 45% of aPL-positive patients. High anti-NET antibody levels are associated with more circulating myeloperoxidase (MPO)-DNA complexes, a biomarker of NETs. When considering clinical manifestations, positive anti-NET IgG was associated with brain white matter lesions even after adjusting for demographic variables and aPL profiles. Anti-NET IgM tracked with complement consumption after controlling for aPL profiles; furthermore, patient serum containing high levels of anti-NET IgM efficiently deposited complement C3d on NETs. As determined by autoantigen microarray, positive testing for anti-NET IgG was significantly associated with several autoantibodies, including those recognizing citrullinated histones, heparan sulfate proteoglycan, laminin, MPO-DNA complexes, and nucleosomes. Anti-NET IgM positivity associated with autoantibodies targeting single-stranded DNA, double-stranded DNA, and proliferating cell nuclear antigen. Conclusion: These data reveal high levels of anti-NET antibodies in 45% of aPL-positive patients, where they potentially activate the complement cascade. While anti-NET IgM may especially recognize DNA in NETs, anti-NET IgG species appear more likely to target NET-associated protein antigens. This article is protected by copyright. All rights reserved.

No This article is protected by copyright. All rights reserved.

Objective: Follow established management guidelines from the ACR and improve adherence to follow-up recommendations for incidental liver lesions (ILLs) for all patients undergoing CT abdomen and pelvis with contrast (CTAPw) examinations, with advocacy from a multidisciplinary care team. Methods: A mandatory structured radiology reporting module was developed for use in CTAPw reports for ILL recommendations. Data from the electronic medical record describing patients with radiology-reported ILLs and their clinical risk diagnosis categories were tabulated in a queryable electronic database. A nurse co-ordinator initiated workflow to communicate the need for ILL follow-up MRI to ordering physicians and primary care providers. MRIs were ordered by the ILL team. An interactive process was undertaken with continuous review to improve identification of eligible patients and adherence to recommendations. Results: During the initial launch phase from December 2020 to March 2021, 1,577 ILLs were detected on 20,667 CTAPw examinations, and for those with the characterize now recommendation, 36 of 114 (31.6%) received follow-up in 30 days. Between January 2021 and June 2022, 117,520 CTAPws were performed and 4,371 ILLs were detected. Using the ILL workflow, in the MRI now cohort, follow-up occurred within 30 days in 202 of 542 (36.2%) patients, and a total of 368 of 542 (67.9%) patients have completed their follow-up to date. Discussion: Using a focused effort to close a gap in ILL care, adherence to follow-up recommendations improved over the long term, although there remains a gap in adherence to short-term interventions. A multidisciplinary approach, radiology reporting, and software solutions were leveraged to improve a complex process.

Background: Valve-in-valve (VIV) transcatheter aortic valve replacement (TAVR) is increasingly used to treat degenerated surgical bioprostheses. Bioprosthetic valve fracture (BVF) has been shown to improve hemodynamic status in VIV TAVR in case series. However, the safety and efficacy of BVF are unknown. Objectives: The primary objective of this study was to assess the safety and efficacy of VIV TAVR using SAPIEN 3 and SAPIEN 3 Ultra valves with or without BVF using data from the Society of Thoracic Surgeons/American College of Cardiology TVT (Transcatheter Valve Therapy) Registry. Methods: The primary outcome was in-hospital mortality. Secondary outcomes included echocardiography-derived valve gradient and aortic valve area. Inverse probability of treatment weighting was used to adjust for baseline characteristics. Results: A total of 2,975 patients underwent VIV TAVR from December 15, 2020, to March 31, 2022. BVF was attempted in 619 patients (21%). In adjusted analyses, attempted BVF was associated with higher in-hospital mortality (OR: 2.51; 95% CI: 1.30-4.84) and life-threatening bleeding (OR: 2.55; 95% CI: 1.44-4.50). At discharge, VIV TAVR with attempted BVF was associated with larger aortic valve area (1.6 cm2 vs 1.4 cm2; P < 0.01) and lower mean gradient (16.3 mm Hg vs 19.2 mm Hg; P < 0.01). When BVF was compared with no BVF according to timing (before vs after transcatheter heart valve implantation), BVF after transcatheter heart valve implantation was associated with improved hemodynamic status and similar mortality. Conclusions: BVF as an adjunct to VIV TAVR with the SAPIEN 3 and SAPIEN 3 Ultra valves is associated with a higher risk for in-hospital mortality and significant bleeding and modest improvements in echocardiography-derived hemodynamic status. The timing of BVF is an important determinant of safety and efficacy.

Objectives: To evaluate whether implementing more restrictive NICU platelet transfusion guidelines following the PlaNeT-2 randomized controlled trial (transfusion threshold changed from 50,000/μL to 25,000/μL for most neonates) was associated with fewer NICU patients receiving a platelet transfusion, without adversely affecting outcomes. Study design: Multi-NICU retrospective analysis of platelet transfusions, patient characteristics, and outcomes during three years before vs. three years after revising system-wide guidelines. Results: During the first period, 130 neonates received one or more platelet transfusions; this fell to 106 during the second. The transfusion rate was 15.9/1000 NICU admissions in the first period vs. 12.9 in the second (p=0.106). During the second period, a smaller proportion of transfusions was administered when the platelet count was in the 50,000 - 100,000/μL range (p=0.017), and a larger proportion when it was <25,000/μL (p=0.083). We also saw a fall in the platelet counts that preceded the order for transfusion from 43,100/μL to 38,000/μL (p=0.044). The incidence of adverse outcomes did not change. Conclusions: Changing platelet transfusion guidelines in a multi-NICU network to a more restrictive practice was not associated with a significant reduction in number of neonates receiving a platelet transfusion. The guideline implementation was associated with a reduction in the mean platelet count triggering a transfusion. We speculate that further reductions in platelet transfusions can safely occur with additional education and accountability tracking.

Forming strategic partnerships is vital to academic health centers to further their missions of patient care, education, research, and community engagement. Formulating a strategy for such partnerships can be daunting due to the complexities of the health care landscape. The authors propose a game theory approach to partnership formation with the players being gatekeepers, facilitators, organizational employees, and economic buyers. Forming an academic partnership is not a game that is typically won or lost but is rather an ongoing engagement. Consistent with our game theory approach, the authors propose six basic rules to assist in successful strategic partnership formation for academic health centers.

Background Guidelines emphasize rapid antibiotic treatment for sepsis, but infection presence is often uncertain at initial presentation. We investigated the incidence and drivers of false-positive presumptive infection diagnosis among emergency department (ED) patients meeting Sepsis-3 criteria. Methods For a retrospective cohort of patients hospitalized after meeting Sepsis-3 criteria (acute organ failure and suspected infection including blood cultures drawn and intravenous antimicrobials administered) in one of 4 EDs from 2013 to 2017, trained reviewers first identified the ED-diagnosed source of infection and adjudicated the presence and source of infection on final assessment. Reviewers subsequently adjudicated final infection probability for a randomly selected 10% subset of subjects. Risk factors for false-positive infection diagnosis and its association with 30-day mortality were evaluated using multivariable regression. Results Of 8,267 patients meeting Sepsis-3 criteria in the ED, 699 (8.5%) did not have an infection on final adjudication, and 1,488 (18.0%) patients with confirmed infections had a different source of infection diagnosed in the ED versus final adjudication (i.e., initial/final source diagnosis discordance). Among the subset of patients whose final infection probability was adjudicated (n=812), 79 (9.7%) had only “possible” infection and 77 (9.5%) were not infected. Factors associated with false-positive infection diagnosis included hypothermia, altered mental status, comorbidity burden, and an “unknown infection source” diagnosis in the ED (OR 6.39, 95% CI 5.14-7.94). False-positive infection diagnosis was not associated with 30-day mortality. Conclusions In this large multihospital study, <20% of ED patients meeting Sepsis-3 criteria had no infection or only possible infection on retrospective adjudication.

Background Evidence on the economic burden of stillbirth is limited. In this systematic review, we aimed to identify studies focusing on the economic burden of stillbirth, describe the methods used, and summarize the findings. Method We performed a systematic search in Medline, EMBASE, Cochrane library, and EconLit from inception to July 2021. Original studies reporting the cost of illness, economic burden, or health care expenditures related to stillbirth were included. Two reviewers independently extracted data and evaluated study quality using the Larg and Moss checklist. A narrative synthesis was performed. Costs were presented in US dollars (US$) in 2020. Results From the 602 records identified, a total of four studies were included. Eligible studies were from high‐income countries. Only one study estimated both direct and indirect costs. Among three cost‐of‐illness studies, two studies undertook a prevalence‐based approach. The quality of these studies varied and was substantially under‐reported. Four studies describing direct costs ranged from $6934 to $9220 per stillbirth. Indirect costs account for around 97% of overall costs. No studies have incorporated intangible cost components. Conclusions The economic burden of stillbirth has been underestimated and not extensively studied. There are no data on the cost of stillbirth from countries that bear a higher burden of stillbirth. Extensive variation in methodologies and cost components was observed in the studies reviewed. Future research should incorporate all costs, including intangible costs, to provide a comprehensive picture of the true economic impact of stillbirth on society.

Purpose The purpose of this exploratory sequential mixed methods study was to describe the sources of informal financial support used by adolescent and young adult (AYA) cancer survivors and how financial toxicity and demographic factors were associated with different types and magnitudes of informal financial support. Methods This analysis is part of a larger health insurance literacy study that included pre-trial interviews and a randomized controlled trial (RCT) for AYA cancer survivors. Eligible study participants were 18 years of age, diagnosed with cancer as an AYA (15–39 years), insured, and for the RCT sample less than 1 year from diagnosis. Interview audio was transcribed, quality checked, and thematically analyzed. RCT baseline and follow-up surveys captured informal financial support use. Chi-squared and Fisher’s exact tests were used to assess differences in informal financial support type use and frequency by financial toxicity and AYA demographics. Results A total of N = 24 and N = 86 AYAs participated in pre-trial interviews and the RCT respectively. Interview participants reported a variety of informal financial support sources including savings, community, family/friends, and fundraisers. However, only half of participants reported their informal financial support to be sufficient. High financial toxicity was associated with the most types of informal financial support and a higher magnitude of use. The lowest income group accessed informal financial supports less frequently than higher income groups. Conclusion Our study demonstrates that AYA survivors experiencing financial toxicity frequently turn to informal sources of financial support and the magnitude is associated with financial toxicity. However, low-income survivors, and other at-risk survivors, may not have access to informal sources of financial support potentially widening inequities.

In 2021, the National Academy of Science, Engineering, and Medicine Committee on Implementing High-Quality Primary Care published its recommendations to expand the provision of high-quality primary care in the USA. These include paying for primary care teams to care for people, ensuring that high-quality primary care is available, training primary care teams where people live and work, and designing information technology that serves the patient, family, and care team. Many of these recommendations echo those of prior calls for action, including the Institute of Medicine's 1996 report. However, the 2021 report recognizes the importance of implementation in its final recommendation of ensuring that high-quality primary care is implemented in the USA. We consider the NASEM recommendations in terms of the complexity of the task of supporting interconnected implementation activities that occur in local contexts. With this vantage point, we identify foundational collective actions, including the creation of an accountable leadership entity, payment reform, and community networks. We then discuss the creation of a monitoring mechanism to assess and support sustained action.

The effectiveness and safety of direct oral anticoagulants (DOAC) compared with warfarin remains uncertain in obese patients. We assessed the comparative effectiveness and safety of DOACs with warfarin for the treatment of VTE among obese patients. This multi-center retrospective cohort study included adults with a BMI ≥ 35 kg/m² or weight ≥ 120 kg prescribed either DOAC (apixaban, dabigatran, edoxaban, rivaroxaban) or warfarin for a VTE diagnosis. The primary outcome was the 12-month rate of recurrent VTE. The secondary outcome was the 12-month rate of major bleeding. Among 5626 patients, 67% were prescribed warfarin and 33% were prescribed a DOAC. The 12-month VTE recurrence rate was 3.6% (67/1823) for patients treated with DOAC compared with 3.8% (143/3664) for patients treated with warfarin [odds ratio for recurrent VTE on warfarin versus DOAC (OR) (95% CI).07 (0.80, 1.45)]. The 12-month major bleeding rate was 0.5% (10/1868) for patients on DOAC versus 2.4% (89/3758) on warfarin [OR 4.25 (2.19, 8.22)]. Similar proportions of recurrent VTE occurred across BMI thresholds on DOAC and warfarin: for BMI ≥ 35 kg/m² (N = 5412), 3.6% versus 3.8%, respectively [OR 1.08 (0.80, 1.46)]; for BMI ≥ 40 kg/m² (N = 2321), 4.4% versus 3.5%, respectively [OR 0.80 (0.51, 1.26)]; and for BMI ≥ 50 kg/m² (N = 560), 3.1% versus 3.7%, respectively [OR 1.18 (0.39, 3.56)]. Similar proportions of recurrent VTE occurred in patients with obesity treated for VTE with DOACs and warfarin. DOACs were associated with lower major bleeding compared to warfarin in patients with obesity and VTE.

Breast cancer (BC) patients with a germline CHEK2 c.1100delC variant have an increased risk of contralateral BC (CBC) and worse BC-specific survival (BCSS) compared to non-carriers. We aimed to assess the associations of CHEK2 c.1100delC, radiotherapy, and systemic treatment with CBC risk and BCSS. Analyses were based on 82,701 women diagnosed with invasive BC including 963 CHEK2 c.1100delC carriers; median follow-up was 9.1 years. Differential associations of treatment by CHEK2 c.1100delC status were tested by including interaction terms in a multivariable Cox regression model. A multi-state model was used for further insight into the relation between CHEK2 c.1100delC status, treatment, CBC risk and death. There was no evidence for differential associations of therapy with CBC risk by CHEK2 c.1100delC status The strongest association with reduced CBC risk was observed for the combination of chemotherapy and endocrine therapy [HR(95%CI): 0.66 (0.55–0.78)]. No association was observed with radiotherapy. Results from the multi-state model showed shorter BCSS for CHEK2 c.1100delC carriers versus non-carriers also after accounting for CBC occurrence [HR(95%CI) :1.30 (1.09–1.56)]. In conclusion, systemic therapy was associated with reduced CBC risk irrespective of CHEK2 c.1100delC status. Moreover, CHEK2 c.1100delC carriers had shorter BCSS, which appears not to be fully explained by their CBC risk. (Main MS: 3201 words)