Publications by authors named "Benjamin Haaland"

99 Publications

Initial Derivation of a Predictive Model for Left Ventricular Longitudinal Strain (LS) in Early Sepsis.

J Intensive Care Med 2021 Nov 10:8850666211053796. Epub 2021 Nov 10.

98078Intermountain Medical Center, Murray, UT, USA.

Septic shock is a common deadly disease often associated with cardiovascular dysfunction. Left ventricular longitudinal strain (LV LS) has been proposed as a sensitive marker to measure cardiovascular function; however, it is not available universally in standard clinical echocardiograms. We sought to derive a predictive model for LV LS, using machine learning techniques with the hope that we may uncover surrogates for LV LS. We found that left ventricular ejection fraction, tricuspid annular plane systolic excursion, sepsis source, height, mitral valve Tei index, LV systolic dimension, aortic valve ejection time, and peak acceleration rate were all predictive of LV LS in this initial exploratory model. Future modeling work may uncover combinations of these variables which may be powerful surrogates for LV LS and cardiovascular function.
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http://dx.doi.org/10.1177/08850666211053796DOI Listing
November 2021

Characteristics and Outcomes of US Patients Hospitalized With COVID-19.

Am J Crit Care 2021 Oct 28:e1-e12. Epub 2021 Oct 28.

Catherine L. Hough is a professor and chief, Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Oregon Health and Science University.

Background: Understanding COVID-19 epidemiology is crucial to clinical care and to clinical trial design and interpretation.

Objective: To describe characteristics, treatment, and outcomes among patients hospitalized with COVID-19 early in the pandemic.

Methods: A retrospective cohort study of consecutive adult patients with laboratory-confirmed, symptomatic SARS-CoV-2 infection admitted to 57 US hospitals from March 1 to April 1, 2020.

Results: Of 1480 inpatients with COVID-19, median (IQR) age was 62.0 (49.4-72.9) years, 649 (43.9%) were female, and 822 of 1338 (61.4%) were non-White or Hispanic/Latino. Intensive care unit admission occurred in 575 patients (38.9%), mostly within 4 days of hospital presentation. Respiratory failure affected 583 patients (39.4%), including 284 (19.2%) within 24 hours of hospital presentation and 413 (27.9%) who received invasive mechanical ventilation. Median (IQR) hospital stay was 8 (5-15) days overall and 15 (9-24) days among intensive care unit patients. Hospital mortality was 17.7% (n=262). Risk factors for hospital death identified by penalized multivariable regression included older age; male sex; comorbidity burden; symptoms-to-admission interval; hypotension; hypoxemia; and higher white blood cell count, creatinine level, respiratory rate, and heart rate. Of 1218 survivors, 221 (18.1%) required new respiratory support at discharge and 259 of 1153 (22.5%) admitted from home required new health care services.

Conclusions: In a geographically diverse early-pandemic COVID-19 cohort with complete hospital folllow-up, hospital mortality was associated with older age, comorbidity burden, and male sex. Intensive care unit admissions occurred early and were associated with protracted hospital stays. Survivors often required new health care services or respiratory support at discharge.
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http://dx.doi.org/10.4037/ajcc2022549DOI Listing
October 2021

Treatment Pattern and Outcomes with Systemic Therapy in Men with Metastatic Prostate Cancer in the Real-World Patients in the United States.

Cancers (Basel) 2021 Sep 30;13(19). Epub 2021 Sep 30.

Division of Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA.

Background: Both novel hormonal therapies and docetaxel are approved for treatment of metastatic prostate cancer (mPC; in castration sensitive or refractory settings). Present knowledge gaps include lack of real-world data on treatment patterns in patients with newly diagnosed mPC, and comparative effectiveness of novel hormonal therapies (NHT) versus docetaxel after treatment with a prior NHT.

Methods: Herein we extracted patient-level data from a large real-world database of patients with mPC in United States. Utilization of NHT or docetaxel for mPC and comparative effectiveness of an alternate NHT versus docetaxel after one prior NHT was evaluated. Comparative effectiveness was examined via Cox proportional hazards model with propensity score matching weights. Each patient's propensity for treatment was modeled via random forest based on 22 factors potentially driving treatment selection.

Results: The majority of patients (54%) received only androgen deprivation therapy for mPC. In patients treated with an NHT, alternate NHT was the most common next therapy and was associated with improved median overall survival over docetaxel (abiraterone followed by docetaxel vs. enzalutamide (8.7 vs. 15.6 months; adjusted hazards ratio; aHR 1.32; = 0.009; and enzalutamide followed by docetaxel vs. abiraterone (9.7 vs. 13.2 months aHR 1.40; = 0.009). Limitations of the study include retrospective design.
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http://dx.doi.org/10.3390/cancers13194951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8508241PMC
September 2021

Efficacy of Selective Laser Trabeculoplasty after iStent Implantation in Primary Open-Angle Glaucoma.

J Pers Med 2021 Aug 16;11(8). Epub 2021 Aug 16.

Department of Ophthalmology, Ross Eye Institute, Jacobs School of Medicine and Biomedical Engineering, SUNY-University at Buffalo, Buffalo, NY 14214, USA.

iStent implantation is thought to augment the trabecular outflow channel in the anterior segment of the eye. We hypothesized that iStent with subsequent selective laser trabeculoplasty (SLT) would better control the intraocular pressure (IOP) compared to standalone SLT in patients with primary open-angle glaucoma (POAG). We, therefore, determined if the presence of an iStent combined with SLT was statistically associated with IOP lowering compared to standalone SLT. Through retrospective electronic medical record review, records of 824 eyes from 440 patients who received primary SLT without a history of iStent were considered. Additionally, 42 eyes from 28 patients who received SLT after combined phacoemulsification and iStent implantation that failed to control intraocular pressure (IOP) and/or the progression of the disease were retrospectively reviewed. IOP and number of medications, which were tracked in each patient for up to 12 months post laser, were also examined. Successful outcome was defined as a statistically significant reduction in IOP or number of medications at 6 months. As defined in univariate analysis ≤ 0.01), multivariate analysis included iStent, age, sex, race, and initial IOP as variables. IOP reduction was statistically associated with patients pre-SLT IOP ( < 0.001) but not with patients with iStent ( = 0.222). Medication reduction was statistically associated with the pre-SLT number of medications ( < 0.001) and iStent ( < 0.001). In eyes that received SLT, iStent was not statistically associated with a greater reduction in IOP compared to controls, but was associated with a higher reduction in the overall number of medications used 6 months after receiving SLT. The work presented should guide clinicians to consider SLT as an effective therapy after iStent implantation, in terms of glaucoma medication reduction in iStent patients, but clinicians should know that the presence of an iStent does not necessarily make subsequent SLT more effective at lowering IOP.
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http://dx.doi.org/10.3390/jpm11080797DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8400945PMC
August 2021

Radium-223 plus Enzalutamide Versus Enzalutamide in Metastatic Castration-Refractory Prostate Cancer: Final Safety and Efficacy Results.

Oncologist 2021 Aug 22. Epub 2021 Aug 22.

Genitourinary Oncology, Huntsman Cancer Institute, Salt Lake City, Utah, USA.

Lessons Learned: Long-term safety of radium-223 with enzalutamide was confirmed in this clinical trial. PSA-PFS2 was prolonged with the combination compared with enzalutamide alone.

Background: Previously, we showed the combination of radium-223 and enzalutamide to be safe and associated with improved efficacy based on a concomitant decline in serum bone metabolism markers compared with enzalutamide alone in a phase II trial of men with metastatic castration-resistant prostate cancer (mCRPC) [1].

Methods: Secondary endpoints were not included in our initial report, and we include them herein, after a median follow-up of 22 months. These objectives included long-term safety, prostate-specific antigen (PSA)-progression-free survival (PFS), and radiographic progression-free survival; PSA-PFS2 (time from start of protocol therapy to PSA progression on subsequent therapy); time to next therapy (TTNT); and overall survival (OS). Survival analysis and log-rank tests were performed using the R statistical package v.4.0.2 (https://www.r-project.org). Statistical significance was defined as p < .05.

Results: Of 47 patients (median age, 68 years), 35 received the combination and 12 enzalutamide alone. After a median follow-up of 22 months, final safety results did not show any increase in fractures or other adverse events in the combination arm. PSA-PFS2 was significantly improved, and other efficacy parameters were numerically improved in the combination over the enzalutamide arm.

Conclusion: The combination of enzalutamide and radium-223 was found to be safe and associated with promising efficacy in men with mCRPC. These hypothesis-generating results portend well for the ongoing phase III PEACE III trial in this setting.
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http://dx.doi.org/10.1002/onco.13949DOI Listing
August 2021

Survival Outcomes Based on Sequence of Therapy Using FOLFIRINOX and Nab-Paclitaxel + Gemcitabine in Metastatic Pancreatic Ductal Adenocarcinoma.

Pancreas 2021 07;50(6):796-802

Medical Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT.

Objectives: Optimal sequence of therapy for patients with metastatic pancreatic ductal adenocarcinoma is unknown. Combination chemotherapy with fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) and nab-paclitaxel + gemcitabine (nab-p/gem) are standard first-line (1L) therapies. They have never been prospectively compared. We retrospectively compared overall survival (OS) of patients treated with 1L nab-p/gem and second-line (2L) FOLFIRINOX with those treated with the reverse sequence.

Methods: Patients with metastatic pancreatic ductal adenocarcinoma treated with 1L FOLFIRINOX and 2L nab-p/gem or vice versa were identified using an electronic health record-derived real-world database. Using an intent-to-treat analysis, we compared OS from initiation of 1L therapy. A Cox model, stratified by deciles of propensity score, estimated the effect of treatment sequence on OS.

Results: The study included 3027 patients. The median OS for 1L FOLFIRINOX versus nab-p/gem was 8.6 versus 6.1 months (hazard ratio, 0.77; 95% confidence interval, 0.70-0.84). The median OS for 1L FOLFIRINOX and 2L nab-p/gem versus 1L nab-p/gem and 2L FOLFIRINOX was 11.9 versus 11.5 months (hazard ratio, 0.97; 95% confidence interval, 0.79-1.18).

Conclusions: In this analysis of real-world data, 1L FOLFIRINOX was associated with increased OS in propensity analysis. For patients who received both FOLFIRINOX and nab-p/gem, median OS was similar regardless of sequence.
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http://dx.doi.org/10.1097/MPA.0000000000001844DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373701PMC
July 2021

Pseudoexfoliation and Cataract Syndrome Associated with Genetic and Epidemiological Factors in a Mayan Cohort of Guatemala.

Int J Environ Res Public Health 2021 07 6;18(14). Epub 2021 Jul 6.

Department of Population Health Sciences, University of Utah School of Medicine, Salt Lake City, UT 84108, USA.

The Mayan population of Guatemala is understudied within eye and vision research. Studying an observational homogenous, geographically isolated population of individuals seeking eye care may identify unique clinical, demographic, environmental and genetic risk factors for blinding eye disease that can inform targeted and effective screening strategies to achieve better and improved health care distribution. This study served to: (a) identify the ocular health needs within this population; and (b) identify any possible modifiable risk factors contributing to disease pathophysiology within this population. We conducted a cross-sectional study with 126 participants. Each participant completed a comprehensive eye examination, provided a blood sample for genetic analysis, and received a structured core baseline interview for a standardized epidemiological questionnaire at the Salama Lions Club Eye Hospital in Salama, Guatemala. Interpreters were available for translation to the patients' native dialect, to assist participants during their visit. We performed a genome-wide association study for ocular disease association on the blood samples using Illumina's HumanOmni2.5-8 chip to examine single nucleotide polymorphism SNPs in this population. After implementing quality control measures, we performed adjusted logistic regression analysis to determine which genetic and epidemiological factors were associated with eye disease. We found that the most prevalent eye conditions were cataracts (54.8%) followed by pseudoexfoliation syndrome (PXF) (24.6%). The population with both conditions was 22.2%. In our epidemiological analysis, we found that eye disease was significantly associated with advanced age. Cataracts were significantly more common among those living in the 10 districts with the least resources. Furthermore, having cataracts was associated with a greater likelihood of PXF after adjusting for both age and sex. In our genetic analysis, the SNP most nominally significantly associated with PXF lay within the gene KSR2 ( < 1 × 10). Several SNPs were associated with cataracts at genome-wide significance after adjusting for covariates ( < 5 × 10). About seventy five percent of the 33 cataract-associated SNPs lie within 13 genes, with the majority of genes having only one significant SNP (5 × 10). Using bioinformatic tools including PhenGenI, the Ensembl genome browser and literature review, these SNPs and genes have not previously been associated with PXF or cataracts, separately or in combination. This study can aid in understanding the prevalence of eye conditions in this population to better help inform public health planning and the delivery of quality, accessible, and relevant health and preventative care within Salama, Guatemala.
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http://dx.doi.org/10.3390/ijerph18147231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8303577PMC
July 2021

First line immunotherapy extends brain metastasis free survival, improves overall survival, and reduces the incidence of brain metastasis in patients with advanced melanoma.

Cancer Rep (Hoboken) 2021 Jun 17:e1419. Epub 2021 Jun 17.

Huntsman Cancer Institute, University of Utah Health Sciences Center, Salt Lake City, Utah, USA.

Background: Recent advances in targeted therapy and immunotherapy have improved the prognosis of melanoma patients but brain metastasis remains a major challenge. Currently, it is unclear how existing therapies can be best used to prevent or treat brain metastasis in melanoma patients.

Aims: We aimed to assess brain metastasis free survival (BMFS), overall survival (OS), incidence of brain metastases, and sequencing strategies of immunotherapy and targeted therapy in patients with BRAF-mutated advanced melanoma.

Methods And Results: We retrospectively analyzed 683 patients with BRAF-mutated advanced melanoma treated with first line (1L) immunotherapy (N = 266) or targeted therapy (N = 417). The primary outcome was BMFS. Secondary outcomes included OS of all patients and incidence of brain metastases in patients without documented brain metastases prior to 1L therapy. The median BMFS was 13.7 months [95% confidence interval (CI): 12.4-16.0] among all patients. The median BMFS for patients receiving 1L immunotherapy was 41.9 months [95% CI: 22.8-not reached (NR)] and targeted therapy was 11.0 months (95% CI: 8.8-12.5). Median OS results were qualitatively similar to BMFS results. The cumulative incidence of brain metastases for patients receiving 1L targeted therapy was higher than for patients receiving 1L immunotherapy (P < .001). Patients receiving 1L anti-CTLA4 plus anti-PD1 combination immunotherapy only or followed by second line (2L) targeted therapy had better BMFS (HR 0.40, 95% CI: 0.24-0.67, P = .001), improved OS (HR 0.49, 95% CI: 0.30-0.81, P = .005), and reduced incidence of brain metastases (HR 0.47, 95% CI: 0.24-0.67, P = .047) than patients receiving 1L combination BRAF and MEK targeted therapy followed by 2L immunotherapy.

Conclusion: Patients with advanced BRAF mutant melanoma treated with 1L immunotherapy have significantly longer BMFS and OS, and reduced incidence of brain metastases, compared with those treated with 1L targeted therapy. Further studies evaluating the ability of immunotherapy and targeted therapy to improve OS and prevent brain metastases are warranted.
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http://dx.doi.org/10.1002/cnr2.1419DOI Listing
June 2021

Understanding the Prevalence of Prediabetes and Diabetes in Patients With Cancer in Clinical Practice: A Real-World Cohort Study.

J Natl Compr Canc Netw 2021 Mar 10;19(6):709-718. Epub 2021 Mar 10.

2Huntsman Cancer Institute, and.

Background: This study aimed to understand the prevalence of prediabetes (preDM) and diabetes mellitus (DM) in patients with cancer overall and by tumor site, cancer treatment, and time point in the cancer continuum.

Methods: This cohort study was conducted at Huntsman Cancer Institute at the University of Utah. Patients with a first primary invasive cancer enrolled in the Total Cancer Care protocol between July 2016 and July 2018 were eligible. Prevalence of preDM and DM was based on ICD code, laboratory tests for hemoglobin A1c, fasting plasma glucose, nonfasting blood glucose, or insulin prescription.

Results: The final cohort comprised 3,512 patients with cancer, with a mean age of 57.8 years at cancer diagnosis. Of all patients, 49.1% (n=1,724) were female. At cancer diagnosis, the prevalence of preDM and DM was 6.0% (95% CI, 5.3%-6.8%) and 12.2% (95% CI, 11.2%-13.3%), respectively. One year after diagnosis the prevalence was 16.6% (95% CI, 15.4%-17.9%) and 25.0% (95% CI, 23.6%-26.4%), respectively. At the end of the observation period, the prevalence of preDM and DM was 21.2% (95% CI, 19.9%-22.6%) and 32.6% (95% CI, 31.1%-34.2%), respectively. Patients with myeloma (39.2%; 95% CI, 32.6%-46.2%) had the highest prevalence of preDM, and those with pancreatic cancer had the highest prevalence of DM (65.1%; 95% CI, 57.0%-72.3%). Patients who underwent chemotherapy, radiotherapy, or immunotherapy had a higher prevalence of preDM and DM compared with those who did not undergo these therapies.

Conclusions: Every second patient with cancer experiences preDM or DM. It is essential to foster interprofessional collaboration and to develop evidence-based practice guidelines. A better understanding of the impact of cancer treatment on the development of preDM and DM remains critical.
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http://dx.doi.org/10.6004/jnccn.2020.7653DOI Listing
March 2021

Comparative Efficacy and Safety of Programmed Death-1 Pathway Inhibitors in Advanced Gastroesophageal Cancers: A Systematic Review and Network Meta-Analysis of Phase III Clinical Trials.

Cancers (Basel) 2021 May 26;13(11). Epub 2021 May 26.

Division of Hematology-Oncology, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33146, USA.

: The use of checkpoint inhibitors has changed the treatment landscape for gastroesophageal cancer in the third-line setting. However, success rates in earlier treatment lines are highly variable across trials. Herein, we compare the efficacy and safety of the different anti-PD-1/PD-L1 regimens with or without chemotherapy; : We performed a network meta-analysis (NMA) of anti-PD-1/PD-L1 monotherapy or combined with chemotherapy (chemoimmunotherapy) for gastroesophageal cancers without ERBB2 overexpression; : The first-line NMA included four trials (N = 3817), showing that chemoimmunotherapy improved OS and PFS without significant safety difference: Nivolumab-chemotherapy, OS (HR: 0.83 [95% CI, 0.75-0.92]), PFS (HR 0.68 [95% CI, 0.57-0.81]), Pembrolizumab-chemotherapy: OS (HR 0.77 [95% CI, 0.67-0.88]), PFS (HR: 0.72 [95% CI, 0.60-0.85]. Pembrolizumab monotherapy was the safest first-line treatment, SAE (OR 0.02 [95% CI, 0.00-0.2]) but showed no survival benefit. The second-line NMA encompassed four trials (N = 2087), showing that anti-PD-1 significantly improved safety but not survival: camrelizumab, SAE (OR 0.37; [95% CI, 0.24-0.56]); nivolumab, SAE (OR 0.13, [95% CI, 0.08-0.2]) pembrolizumab, SAE (OR 0.4; [95% CI, 0.30-0.53]); : chemoimmunotherapy improves OS and PFS in previously untreated gastroesophageal cancers. Anti-PD-1 monotherapies improve safety in refractory disease, with no significant survival benefit.
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http://dx.doi.org/10.3390/cancers13112614DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199431PMC
May 2021

Decision fatigue in low-value prostate cancer screening.

Cancer 2021 Sep 27;127(18):3343-3353. Epub 2021 May 27.

Division of Urology, Department of Surgery, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah.

Background: Low-value prostate-specific antigen (PSA) testing is common yet contributes substantial waste and downstream patient harm. Decision fatigue may represent an actionable target to reduce low-value urologic care. The objective of this study was to determine whether low-value PSA testing patterns by outpatient clinicians are consistent with decision fatigue.

Methods: Outpatient appointments for adult men without prostate cancer were identified at a large academic health system from 2011 through 2018. The authors assessed the association of appointment time with the likelihood of PSA testing, stratified by patient age and appropriateness of testing based on clinical guidelines. Appointments included those scheduled between 8:00 am and 4:59 pm, with noon omitted. Urologists were examined separately from other clinicians.

Results: In 1,581,826 outpatient appointments identified, the median patient age was 54 years (interquartile range, 37-66 years), 1,256,152 participants (79.4%) were White, and 133,693 (8.5%) had family history of prostate cancer. PSA testing would have been appropriate in 36.8% of appointments. Clinicians ordered testing in 3.6% of appropriate appointments and in 1.8% of low-value appointments. Appropriate testing was most likely at 8:00 am (reference group). PSA testing declined through 11:00 am (odds ratio [OR], 0.57; 95% CI, 0.50-0.64) and remained depressed through 4:00 pm (P < .001). Low-value testing was overall less likely (P < .001) and followed a similar trend, declining steadily from 8:00 am (OR, 0.48; 95% CI, 0.42-0.56) through 4:00 pm (P < .001; OR, 0.23; 95% CI, 0.18-0.30). Testing patterns in urologists were noticeably different.

Conclusions: Among most clinicians, outpatient PSA testing behaviors appear to be consistent with decision fatigue. These findings establish decision fatigue as a promising, actionable target for reducing wasteful and low-value practices in routine urologic care.

Lay Summary: Decision fatigue causes poorer choices to be made with repetitive decision making. This study used medical records to investigate whether decision fatigue influenced clinicians' likelihood of ordering a low-value screening test (prostate-specific antigen [PSA]) for prostate cancer. In more than 1.5 million outpatient appointments by adult men without prostate cancer, the chances of both appropriate and low-value PSA testing declined as the clinic day progressed, with a larger decline for appropriate testing. Testing patterns in urologists were different from those reported by other clinicians. The authors conclude that outpatient PSA testing behaviors appear to be consistent with decision fatigue among most clinicians, and interventions may reduce wasteful testing and downstream patient harms.
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http://dx.doi.org/10.1002/cncr.33644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8497012PMC
September 2021

Evaluation of Oncology Hospital at Home: Unplanned Health Care Utilization and Costs in the Huntsman at Home Real-World Trial.

J Clin Oncol 2021 08 17;39(23):2586-2593. Epub 2021 May 17.

Huntsman Cancer Institute, University of Utah, Salt Lake City, UT.

Purpose: Patients with cancer experience high rates of morbidity and unplanned health care utilization and may benefit from new models of care. We evaluated an adult oncology hospital at home program's rate of unplanned hospitalizations and health care costs and secondarily, emergency department (ED) use, length of hospital stays, and intensive care unit (ICU) admissions during the 30 days after enrollment.

Methods: We conducted a prospective, nonrandomized, real-world cohort comparison of 367 hospitalized patients with cancer-169 patients consecutively admitted after hospital discharge to Huntsman at Home (HH), a hospital-at-home program, compared with 198 usual care patients concurrently identified at hospital discharge. All patients met clinical criteria for HH admission, but those in usual care lived outside the HH service area. Primary outcomes were the number of unplanned hospitalizations and costs during the 30 days after enrollment. Secondary outcomes included length of hospital stays, ICU admissions, and ED visits during the 30 days after enrollment.

Results: Groups were comparable except that more women received HH care. In propensity-weighted analyses, the odds of unplanned hospitalizations was reduced in the HH group by 55% (odds ratio, 0.45, 95% CI, 0.29 to 0.70; < .001) and health care costs were 47% lower (mean cost ratio, 0.53; 95% CI, 0.39 to 0.72; < .001) over the 30-day period. Secondary outcomes also favored HH. Total hospital stay days were reduced by 1.1 days ( = .004) and ED visits were reduced by 45% (odds ratio, 0.55; 95% CI, 0.33 to 0.92; = .022). There was no evidence of a difference in ICU admissions ( = .972).

Conclusion: This oncology hospital at home program shows initial promise as a model for oncology care that may lower unplanned health care utilization and health care costs.
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http://dx.doi.org/10.1200/JCO.20.03609DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8478372PMC
August 2021

Longitudinal visual field variability and the ability to detect glaucoma progression in black and white individuals.

Br J Ophthalmol 2021 May 13. Epub 2021 May 13.

Ophthalmology, Vision, Imaging and Performance (VIP) Laboratory, Duke Eye Center, Durham, North Carolina, USA

Background/aims: To investigate racial differences in the variability of longitudinal visual field testing in a 'real-world' clinical population, evaluate how these differences are influenced by socioeconomic status, and estimate the impact of differences in variability on the time to detect visual field progression.

Methods: This retrospective observational cohort study used data from 1103 eyes from 751 White individuals and 428 eyes from 317 black individuals. Linear regression was performed on the standard automated perimetry mean deviation values for each eye over time. The SD of the residuals from the trend lines was calculated and used as a measure of variability for each eye. The association of race with the SD of the residuals was evaluated using a multivariable generalised estimating equation model with an interaction between race and zip code income. Computer simulations were used to estimate the time to detect visual field progression in the two racial groups.

Results: Black patients had larger visual field variability over time compared with white patients, even when adjusting for zip code level socioeconomic variables (SD of residuals for Black patients=1.53 dB (95% CI 1.43 to 1.64); for white patients=1.26 dB (95% CI 1.14 to 1.22); mean difference: 0.28 (95% CI 0.15 to 0.41); p<0.001). The difference in visual field variability between black and white patients was greater at lower levels of income and led to a delay in detection of glaucoma progression.

Conclusion: Black patients had larger visual field variability compared with white patients. This relationship was strongly influenced by socioeconomic status and may partially explain racial disparities in glaucoma outcomes.
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http://dx.doi.org/10.1136/bjophthalmol-2020-318104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8589883PMC
May 2021

Psoriasis Characteristics for the Early Detection of Psoriatic Arthritis.

J Rheumatol 2021 10 15;48(10):1559-1565. Epub 2021 Apr 15.

B. Haaland, PhD, B.J. Feng, PhD, School of Medicine, and Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, USA.

Objective: Delays in the diagnosis and treatment of psoriatic arthritis (PsA) are common. These delays contribute to impairments in quality of life and joint damage. This study aims to calculate the incidence rate of PsA over time and identify clinical features that may be used for PsA prediction in patients with psoriasis (PsO).

Methods: The study population for PsA incidence analysis included 1128 participants enrolled in the Utah Psoriasis Initiative between 2002 and 2014. Clinical evaluation and medical record review were performed to identify new cases of PsA after enrollment. To identify PsO features associated with PsA, the population was restricted to 627 participants who did not have PsA before PsO phenotyping and had been followed up for subsequent PsA diagnosis. We conducted Cox proportional hazard regressions to estimate the HR of PsA associated with PsO characteristics and other health-related features.

Results: PsA incidence rate increased for > 60 years following PsO onset (trend < 0.0001). There was a significant association between PsA and induration severity in untreated lesions ( < 0.001, HR 1.46), history of fingernail involvement ( < 0.001, HR 2.38), pustular PsO ( < 0.001, HR 3.32), fingernail involvement at enrollment ( < 0.001, HR 2.04), and Koebner phenomenon ( < 0.001, HR 1.90). Multivariate analysis yielded a model that included a history of fingernail involvement ( < 0.001, HR 2.16) and untreated induration ( < 0.001, HR 1.41).

Conclusion: Risk of PsA increases steadily for > 60 years following PsO onset. Patient-reported history of PsO characteristics has greater predictive power than physician-measured features at enrollment visits. The characteristics identified in this study provide guidance for screening for PsA risk in patients with PsO.
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http://dx.doi.org/10.3899/jrheum.201123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8487898PMC
October 2021

Experiences of a Health System's Faculty, Staff, and Trainees' Career Development, Work Culture, and Childcare Needs During the COVID-19 Pandemic.

JAMA Netw Open 2021 04 1;4(4):e213997. Epub 2021 Apr 1.

Department of Population Health Sciences, University of Utah, Salt Lake City.

Importance: In March 2020, US public buildings (including schools) were shut down because of the COVID-19 pandemic, and 42% of US workers resumed their employment duties from home. Some shutdowns remain in place, yet the extent of the needs of US working parents is largely unknown.

Objective: To identify and address the career development, work culture, and childcare needs of faculty, staff, and trainees at an academic medical center during a pandemic.

Design, Setting, And Participants: For this survey study, between August 5 and August 20, 2020, a Qualtrics survey was emailed to all faculty, staff, and trainees at University of Utah Health, an academic health care system that includes multiple hospitals, community clinics, and specialty centers. Participants included 27 700 University of Utah Health faculty, staff, and trainees who received a survey invitation. Data analysis was performed from August to November 2020.

Main Outcomes And Measures: Primary outcomes included experiences of COVID-19 and their associations with career development, work culture, and childcare needs.

Results: A total of 5030 participants completed the entire survey (mean [SD] age, 40 [12] years); 3738 (75%) were women; 4306 (86%) were White or European American; 561 (11%) were Latino or Latina (of any race), Black or African American, American Indian, Alaska Native, and Native Hawaiian or Pacific Islander; and 301 (6%) were Asian or Asian American. Of the participants, 2545 (51%) reported having clinical responsibilities, 2412 (48%) had at least 1 child aged 18 years or younger, 3316 (66%) were staff, 791 (16%) were faculty, and 640 (13%) were trainees. Nearly one-half of parents reported that parenting (1148 participants [49%]) and managing virtual education for children (1171 participants [50%]) were stressors. Across all participants, 1061 (21%) considered leaving the workforce, and 1505 (30%) considered reducing hours. Four hundred forty-nine faculty (55%) and 397 trainees (60%) perceived decreased productivity, and 2334 participants (47%) were worried about COVID-19 impacting their career development, with 421 trainees (64%) being highly concerned.

Conclusions And Relevance: In this survey of 5030 faculty, staff, and trainees of a US health system, many participants with caregiving responsibilities, particularly women, faculty, trainees, and (in a subset of cases) those from racial/ethnic groups that underrepresented in medicine, considered leaving the workforce or reducing hours and were worried about their career development related to the pandemic. It is imperative that medical centers support their employees and trainees during this challenging time.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.3997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019096PMC
April 2021

Real World Characterization of Advanced Non-Small Cell Lung Cancer in Never Smokers by Actionable Mutation Status.

Clin Lung Cancer 2021 07 26;22(4):260-267.e2. Epub 2021 Jan 26.

Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT. Electronic address:

Background: Non-small cell lung cancer (NSCLC) in never-smokers (NS) is vastly different from those with a smoking history in terms of etiology, driver mutations, and immunotherapy responsiveness. This study compares the real-world overall survival (OS) of NSCLC patients by smoking history and mutation status.

Methods: The study included 30,310 advanced or metastatic NSCLC patients in the Flatiron Health EHR-derived database who received biomarker testing results (EGFR, ALK, ROS1, and BRAF), and initiated therapy between 2011 and 2017, with follow up through June 2018. OS by smoking and driver mutation groups was summarized via Kaplan-Meier survival estimates, and compared in the context of a multivariate Cox proportional hazard model.

Results: OS differed by smoking and driver-mutation categories (adjusted and stratified P< .001). The median OS for wild-type (WT) smoking patients was 9.6 months, for mutated (MT) smokers was 19.4 months (adjusted and stratified hazard ratio [HR] relative to WT smokers 0.65; 95% CI 0.60-0.71), for WT NS was 15.1 months (HR 0.78; 95% CI 0.73-0.83 relative to WT smokers), and for MT NS was 25.5 months (HR 0.52; 95% CI 0.48-0.58 relative to WT smokers).

Conclusion: NS with NSCLC survived longer than those with smoking history, in both groups of WT and mutation-positive patients. Findings highlight that in NSCLC patients, a history of never smoking may have similar effect on hazard of death as the presence of an actionable mutation. Taken together, differences in heredity, mutations, and biologic history suggest that NS lung cancer is a distinct clinical entity and must be managed accordingly.
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http://dx.doi.org/10.1016/j.cllc.2021.01.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8310892PMC
July 2021

A modular approach to integrating multiple data sources into real-time clinical prediction for pediatric diarrhea.

Elife 2021 Feb 2;10. Epub 2021 Feb 2.

Division of Infectious Diseases, Department of Internal Medicine, University of Utah, Salt Lake City, United States.

Traditional clinical prediction models focus on parameters of the individual patient. For infectious diseases, sources external to the patient, including characteristics of prior patients and seasonal factors, may improve predictive performance. We describe the development of a predictive model that integrates multiple sources of data in a principled statistical framework using a post-test odds formulation. Our method enables electronic real-time updating and flexibility, such that components can be included or excluded according to data availability. We apply this method to the prediction of etiology of pediatric diarrhea, where 'pre-test' epidemiologic data may be highly informative. Diarrhea has a high burden in low-resource settings, and antibiotics are often over-prescribed. We demonstrate that our integrative method outperforms traditional prediction in accurately identifying cases with a viral etiology, and show that its clinical application, especially when used with an additional diagnostic test, could result in a 61% reduction in inappropriately prescribed antibiotics.
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http://dx.doi.org/10.7554/eLife.63009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7853717PMC
February 2021

Real-world experience with elective discontinuation of PD-1 inhibitors at 1 year in patients with metastatic melanoma.

J Immunother Cancer 2021 01;9(1)

Department of Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, USA

Background: Randomized trials evaluating programmed cell death protein 1 (PD-1) inhibitors in metastatic melanoma either permitted treatment for 2 years (pembrolizumab) or more (nivolumab). The optimal duration of therapy is currently unknown due to limited data, and shorter therapies may be effective.

Methods: Data of patients with metastatic cutaneous melanoma treated with single-agent PD-1 inhibitors at Huntsman Cancer Institute from January 1, 2015, to December 31, 2018, was reviewed to identify a continuous series of patients who made the joint decision with their provider to electively discontinue therapy at 1 year (>6 months and <18 months) in the setting of ongoing treatment response or disease stability. Patients were excluded if they received PD-1 inhibitors with other systemic therapy, had prior exposure to PD-1 therapy, or discontinued treatment due to disease progression or immune-related adverse event. Best objective response (BOR) per RECIST V.1.1 at treatment discontinuation, progression-free survival (PFS), and retreatment characteristics was analyzed.

Results: Of 480 patients who received PD-1 inhibitors, 52 met the inclusion criteria. The median treatment duration from first to the last dose was 11.1 months (95% CI 10.5 to 11.4). BOR was complete response in 13 (25%), partial response in 28 (53.8%), and stable disease in 11 (21.2%) patients. After a median follow-up of 20.5 months (range 3-49.2) from treatment discontinuation, 39 (75%) patients remained without disease progression, while 13 (25%) had progression (median PFS 3.9 months; range 0.7-30.9). On multivariable analysis, younger age, history of brain metastasis, and higher lactate dehydrogenase at the time of anti-PD-1 discontinuation were associated with recurrence. Patients with recurrent melanoma were managed with localized treatment, anti-PD-1 therapies, and BRAF-MEK inhibitors. All patients except one were alive at data cutoff.

Conclusion: In this large real-world, observational cohort study, the majority of patients with metastatic melanoma after 1 year of anti-PD-1 therapy remained without progression on long-term follow-up. The risk of disease progression even in patients with residual disease on imaging was low. After prospective validation, elective PD-1 discontinuation at 1 year may reduce financial and immunotherapy-related toxicity without sacrificing outcomes.
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http://dx.doi.org/10.1136/jitc-2020-001781DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7843310PMC
January 2021

Endocrine therapy and radiotherapy use among older women with hormone receptor-positive, clinically node-negative breast cancer.

Breast Cancer Res Treat 2021 May 9;187(1):287-294. Epub 2021 Jan 9.

Division of Oncology, Department of Internal Medicine, University of Utah, 2000 Circle of Hope Dr., Salt Lake City, UT, 84112, USA.

Purpose: To examine patterns of radiotherapy (RT) and endocrine therapy (ET) use, associations between RT omission and ET adherence, and associations among ET and RT use and disease recurrence in older women with early-stage, estrogen receptor-positive breast cancer.

Methods: Women age 65 and older diagnosed with hormone receptor-positive, clinically node-negative breast cancer between 2005 and 2018 and who did not undergo mastectomy were included. Multinomial logistic regression was used to examine the trends in practice patterns over time and by age. Kaplan-Meier estimates were used to estimate the probability of ET discontinuation. Cox proportional hazards models were constructed to assess associations between recurrence and ET/RT.

Results: Of the 484 enrolled patients, 47.9% patients underwent RT and initiated ET, 27.4% received ET alone, 10.2% received RT alone, and 13.8% patients received neither. Older patients had a higher probability of receiving ET alone or neither ET nor RT (both p < 0.001). The probability of initiating ET was greater among patients who underwent RT than those who omitted RT (p < 0.001). Regardless of RT status (RT or no RT), initiation and continuation of ET may be associated with reduced risk of recurrence.

Conclusion: Patients who opt for no adjuvant therapy, or who do not tolerate ET, are at increased risk of disease recurrence if they omit RT. Clinicians should consider the likelihood a patient will adhere to ET prior to recommending omission of RT.
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http://dx.doi.org/10.1007/s10549-020-06071-wDOI Listing
May 2021

A time-varying model of the dynamics of smoking lapse.

Health Psychol 2021 Jan;40(1):40-50

Center for Health Outcomes and Population Equity, Huntsman Cancer Institute, University of Utah.

Objective: The majority of smokers who make a quit attempt experience their first lapse within the first week of quitting, yet limited research to date has examined how the strength and direction of the relationship between smoking risk factors and lapse may change over longer periods of time. Time-varying effect modeling (TVEM) was used to address this gap.

Method: A diverse sample (N = 325) of adult smokers completed ecological momentary assessments of risk factors for lapse for 28 days after quitting. TVEM was used to examine the relationship between risk factors (abstinence self-efficacy, positive affect, positive coping expectancies, smoking expectancies, motivation, negative affect, stress, and urge) and lapse for 28 days postquit.

Results: Some associations were stable (e.g., negative affect, motivation), whereas others varied over time. Abstinence self-efficacy, positive affect, and positive coping expectancies were most strongly associated with lapse between Days 3 and 8 postquit. The association of urge with lapse was strongest between Days 4 and 10, as well as near the end of the quit attempt. Stress was also most strongly associated with lapse near the beginning and end of the postquit period and was the only predictor associated with lapse on quit date. The strength of the association between smoking expectancies and lapse increased over time.

Conclusion: There may be periods during a quit attempt when certain risk factors are more strongly related to lapse. This work has relevance for tailoring interventions designed to deliver intervention components in particular contexts or times of need. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
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http://dx.doi.org/10.1037/hea0001036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8265776PMC
January 2021

Impact of Implementation of the Core Elements of Outpatient Antibiotic Stewardship Within Veterans Health Administration Emergency Departments and Primary Care Clinics on Antibiotic Prescribing and Patient Outcomes.

Clin Infect Dis 2021 09;73(5):e1126-e1134

Medicine Service Spivak (Sarah Hall is Primary Care), VA Salt Lake City Healthcare System, Salt Lake City, Utah, USA.

Background: The Core Elements of Outpatient Antibiotic Stewardship provide a framework to improve antibiotic use. We report the impact of core elements implementation within Veterans Health Administration sites.

Methods: In this quasiexperimental controlled study, effects of an intervention targeting antibiotic prescription for uncomplicated acute respiratory tract infections (ARIs) were assessed. Outcomes included per-visit antibiotic prescribing, treatment appropriateness, ARI revisits, hospitalization, and ARI diagnostic changes over a 3-year pre-implementation period and 1-year post-implementation period. Logistic regression adjusted for covariates (odds ratio [OR], 95% confidence interval [CI]) and a difference-in-differences analysis compared outcomes between intervention and control sites.

Results: From 2014-2019, there were 16 712 and 51 275 patient visits within 10 intervention and 40 control sites, respectively. Antibiotic prescribing rates pre- and post-implementation within intervention sites were 59.7% and 41.5%, compared to 73.5% and 67.2% within control sites, respectively (difference-in-differences, P < .001). Intervention site pre- and post-implementation OR to receive appropriate therapy increased (OR, 1.67; 95% CI, 1.31-2.14), which remained unchanged within control sites (OR,1.04; 95% CI, .91-1.19). ARI-related return visits post-implementation (-1.3% vs -2.0%; difference-in-differences P = .76) were not different, but all-cause hospitalization was lower within intervention sites (-0.5% vs -0.2%; difference-in-differences P = .02). The OR to diagnose non-specific ARI compared with non-ARI diagnoses increased post-implementation forintervention (OR, 1.27; 95% CI, 1.21 -1.34) but not control (OR, 0.97; 95% CI, .94-1.01) sites.

Conclusions: Implementation of the core elements was associated with reduced antibiotic prescribing for RIs and a reduction in hospitalizations. Diagnostic coding changes were observed.
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http://dx.doi.org/10.1093/cid/ciaa1831DOI Listing
September 2021

The Serine Protease HTRA-1 Is a Biomarker for ROP and Mediates Retinal Neovascularization.

Front Mol Neurosci 2020 17;13:605918. Epub 2020 Nov 17.

Department of Ophthalmology and Visual Sciences, University of Utah, Salt Lake City, UT, United States.

Retinopathy of prematurity (ROP) is a blinding aberrancy of retinal vascular maturation in preterm infants. Despite delayed onset after preterm birth, representing a window for therapeutic intervention, we cannot prevent or cure ROP blindness. A natural form of ROP protection exists in the setting of early-onset maternal preeclampsia, though is not well characterized. As ischemia is a central feature in both ROP and preeclampsia, we hypothesized that angiogenesis mediators may underlie this protection. To test our hypothesis we analyzed peripheral blood expression of candidate proteins with suggested roles in preeclamptic and ROP pathophysiology and with a proposed angiogenesis function (HTRA-1, IGF-1, TGFβ-1, and VEGF-A). Analysis in a discovery cohort of 40 maternal-infant pairs found that elevated HTRA-1 (high-temperature requirement-A serine peptidase-1) was significantly associated with increased risk of ROP and the absence of preeclampsia, thus fitting a model of preeclampsia-mediated ROP protection. We validated these findings and further demonstrated a dose-response between systemic infant HTRA-1 expression and risk for ROP development in a larger and more diverse validation cohort consisting of preterm infants recruited from two institutions. Functional analysis in the oxygen-induced retinopathy (OIR) murine model of ROP supported our systemic human findings at the local tissue level, demonstrating that HtrA-1 expression is elevated in both the neurosensory retina and retinal pigment epithelium by RT-PCR in the ROP disease state. Finally, transgenic mice over-expressing HtrA-1 demonstrate greater ROP disease severity in this model. Thus, HTRA-1 may underlie ROP protection in preeclampsia and represent an avenue for disease , which does not currently exist.
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http://dx.doi.org/10.3389/fnmol.2020.605918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7705345PMC
November 2020

Systemic Disease and Ocular Comorbidity Analysis of Geographically Isolated Federally Recognized American Indian Tribes of the Intermountain West.

J Clin Med 2020 Nov 7;9(11). Epub 2020 Nov 7.

Department of Ophthalmology and Visual Sciences, University of Utah, Salt Lake City, UT 84132, USA.

Background: The American Indian Navajo and Goshute peoples are underserved patient populations residing in the Four Corners area of the United States and Ibupah, Utah, respectively.

Methods: We conducted a cross-sectional study of epidemiological factors and lipid biomarkers that may be associated with type II diabetes, hypertension and retinal manifestations in tribal and non-tribal members in the study areas (n = 146 participants). We performed multivariate analyses to determine which, if any, risk factors were unique at the tribal level. Fundus photos and epidemiological data through standardized questionnaires were collected. Blood samples were collected to analyze lipid biomarkers. Univariate analyses were conducted and statistically significant factors at < 0.10 were entered into a multivariate regression.

Results: Of 51 participants for whom phenotyping was available, from the Four Corners region, 31 had type II diabetes (DM), 26 had hypertension and 6 had diabetic retinopathy (DR). Of the 64 participants from Ibupah with phenotyping available, 20 had diabetes, 19 had hypertension and 6 had DR. Navajo participants were less likely to have any type of retinopathy as compared to Goshute participants (odds ratio (OR) = 0.059; 95% confidence interval (CI) = 0.016-0.223; < 0.001). Associations were found between diabetes and hypertension in both populations. Older age was associated with hypertension in the Four Corners, and the Navajo that reside there on the reservation, but not within the Goshute and Ibupah populations. Combining both the Ibupah, Utah and Four Corners study populations, being American Indian ( = 0.022), residing in the Four Corners ( = 0.027) and having hypertension ( < 0.001) increased the risk of DM. DM ( < 0.001) and age ( = 0.002) were significantly associated with hypertension in both populations examined. When retinopathy was evaluated for both populations combined, hypertension ( = 0.037) and living in Ibupah ( < 0.001) were associated with greater risk of retinopathy. When combining both American Indian populations from the Four Corners and Ibupah, those with hypertension were more likely to have DM ( < 0.001). No lipid biomarkers were found to be significantly associated with any disease state.

Conclusions: We found different comorbid factors with retinal disease outcome between the two tribes that reside within the Intermountain West. This is indicated by the association of tribe and with the type of retinopathy outcome when we combined the populations of American Indians. Overall, the Navajo peoples and the Four Corners had a higher prevalence of chronic disease that included diabetes and hypertension than the Goshutes and Ibupah. To the best of our knowledge, this is the first study to conduct an analysis for disease outcomes exclusively including the Navajo and Goshute tribe of the Intermountain West.
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http://dx.doi.org/10.3390/jcm9113590DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694968PMC
November 2020

Hydroxychloroquine vs. Azithromycin for Hospitalized Patients with COVID-19 (HAHPS): Results of a Randomized, Active Comparator Trial.

Ann Am Thorac Soc 2020 Nov 9. Epub 2020 Nov 9.

University of Utah School of Medicine, 12348, Study Design and Biostatistics Center and Division of Epidemiology, Salt Lake City, Utah, United States.

Rationale: The COVID-19 pandemic struck an immunologically naïve, globally interconnected population. In the face of a new infectious agent causing acute respiratory failure for which there were no known effective therapies, rapid, often pragmatic trials were necessary to evaluate potential treatments, frequently starting with medications that are already marketed for other indications. Early in the pandemic, hydroxychloroquine and azithromycin were two such candidates.

Objective: Assess the relative efficacy of hydroxychloroquine and azithromycin among hospitalized patients with COVID-19.

Methods: We performed a randomized clinical trial of hydroxychloroquine vs. azithromycin among hospitalized patients with COVID-19. Treatment was 5 days of study medication. The primary endpoint was the COVID Ordinal Outcomes scale at day 14. Secondary endpoints included hospital-, ICU-, and ventilator-free days at day 28. The trial was stopped early after enrollment of 85 patients when a separate clinical trial concluded that a clinically important effect of hydroxychloroquine over placebo was definitively excluded. Comparisons were made a priori using a proportional odds model from a Bayesian perspective.

Results: We enrolled 85 patients at 13 hospitals over 11 weeks. Adherence to study medication was high. The estimated odds ratio for less favorable status on the ordinal scale for hydroxychloroquine vs. azithromycin from the primary analysis was 1.07, with a 95% credible interval from 0.63 to 1.83 with a posterior probability of 60% that hydroxychloroquine was worse than azithryomycin. Secondary outcomes displayed a similar, slight preference for azithromycin over hydroxychloroquine. QTc prolongation was rare and did not differ between groups. The twenty safety outcomes were similar between arms with the possible exception of post-randomization onset acute kidney injury, which was more common with hydroxychloroquine (15% vs. 0%). Patients in the hydroxychloroquine arm received remdesivir more often than in the azithromycin arm (19% vs. 2%). There was no apparent association between remdesivir use and acute kidney injury.

Conclusions: While early termination limits the precision of our results, we found no suggestion of substantial efficacy for hydroxychloroquine over azithromycin. Acute kidney injury may be more common with hydroxychloroquine than azithromycin, although this may be due to the play of chance. Differential use of remdesivir may have biased our results in favor of hydroxychloroquine. Our results are consistent with conclusions from other trials that hydroxychloroquine cannot be recommended for inpatients with COVID-19; azithromycin may merit additional investigation.

Clinical Trial Registration: This trial was prospectively registered (NCT04329832) before enrollment of the first patient.
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http://dx.doi.org/10.1513/AnnalsATS.202008-940OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009003PMC
November 2020

Risk of malignancies in patients with spondyloarthritis treated with biologics compared with those treated with non-biologics: a systematic review and meta-analysis.

Ther Adv Musculoskelet Dis 2020 28;12:1759720X20925696. Epub 2020 May 28.

Level 4, Programme in Health Services & Systems Research, Duke NUS Medical-School, 8 College Road, Singapore 169857, Republic of Singapore.

Background: The aim of our study was to synthesize evidence on the occurrence of malignancy in spondyloarthritis (SpA), from randomized controlled trials (RCTs) comparing biologics with non-biologics and biologics to each other.

Methods: We systematically searched Medline, Cochrane Library, EMBASE, Scopus and ClinicalTrials.gov from inception until 31 October 2018. RCTs with ⩾24-week follow-up were included. We extracted data using standardized forms and assessed the risk of bias using the Cochrane Risk of Bias Tool. We performed pair-wise meta-analyses and network meta-analyses to compare the risk of malignancy for each biologics class and SpA type. We reported the Peto odds ratio (OR) of any malignancy along with 95% confidence intervals (95% CI). Bayesian posterior probabilities comparing risk of malignancy of each biologic class with non-biologics were computed as supplementary measures.

Results: Fifty-four trials were included; most (44/54) had follow-up <1 year. Among 14,245 patients, 63 developed a malignancy. While most Peto ORs were >1, they had wide 95% CI and  >0.05. The overall Peto OR comparing biologics with non-biologics was 1.42 (95% CI 0.80-2.53). Only interleukin-17 inhibitors in peripheral SpA had  <0.05 (Peto OR 2.77, 95% CI 1.07-7.13); the posterior probability that the risk was higher than non-biologics was 98%. Stratified analyses revealed no consistent trend by prior exposure to biologics, duration of follow-up, study quality, study-arm crossover, analytical approaches and type of malignancy.

Conclusions: Our findings indicate no overall elevated risk of malignancy with biologics in SpA. As our meta-analyses are unable to conclude on the long-term risk, long-term pharmacovigilance of biologics in SpA may still be warranted.
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http://dx.doi.org/10.1177/1759720X20925696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7573508PMC
May 2020

Comparative Effectiveness of Immune Checkpoint Inhibitors in Patients with Platinum Refractory Advanced Urothelial Carcinoma.

J Urol 2021 03 20;205(3):709-717. Epub 2020 Oct 20.

Division of Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah.

Purpose: Five programmed cell death protein 1 or its ligand (L1) inhibitors are approved for treatment of platinum refractory, locally advanced/unresectable or metastatic urothelial carcinoma. However, their comparative effectiveness is unknown. We compared time to initiation of third therapy or death, and overall survival with different programmed cell death protein 1/L1 inhibitors in patients with platinum refractory metastatic urothelial carcinoma.

Materials And Methods: Patientlevel data were extracted from a real-world de-identified database. Comparative effectiveness was inferred via Cox proportional hazards model, weighted by matching weights. Each patient's propensity for each treatment was modeled via random forest, based on potential drivers of treatment selection. A propensity score for each therapy was used to calculate a matching weight, targeting the same estimand as 1:1 matching of treatment groups with balance among potential confounders. Eligibility criteria included diagnosis of metastatic urothelial carcinoma, receipt of first line treatment with a platinum based chemotherapy, followed by initiation of single agent programmed cell death protein 1/L1 inhibitor after disease progression from August 1, 2016 through May 1, 2019.

Results: Overall, 609 patients were eligible for analysis. Median time to initiation of third therapy or death with atezolizumab, nivolumab and pembrolizumab was 4.2, 5.3 and 4.5 months, respectively, and median overall survival was 6.4, 8.0 and 8.3 months, respectively. Matching weighted analyses did not show strong evidence of differences among programmed cell death protein 1/L1 inhibitors in terms of time to initiation of third therapy or death and overall survival.

Conclusions: In this large real-world cohort, effectiveness in terms of time to initiation of third therapy or death and overall survival with programmed cell death protein 1/L1 inhibitors in patients with platinum refractory locally advanced/unresectable or metastatic urothelial carcinoma was similar.
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http://dx.doi.org/10.1097/JU.0000000000001412DOI Listing
March 2021

Clinical predictors for etiology of acute diarrhea in children in resource-limited settings.

PLoS Negl Trop Dis 2020 10 9;14(10):e0008677. Epub 2020 Oct 9.

Division of Infectious Diseases, Department of Internal Medicine, University of Utah, Salt Lake City, UT, United States of America.

Background: Diarrhea is one of the leading causes of childhood morbidity and mortality in lower- and middle-income countries. In such settings, access to laboratory diagnostics are often limited, and decisions for use of antimicrobials often empiric. Clinical predictors are a potential non-laboratory method to more accurately assess diarrheal etiology, the knowledge of which could improve management of pediatric diarrhea.

Methods: We used clinical and quantitative molecular etiologic data from the Global Enteric Multicenter Study (GEMS), a prospective, case-control study, to develop predictive models for the etiology of diarrhea. Using random forests, we screened the available variables and then assessed the performance of predictions from random forest regression models and logistic regression models using 5-fold cross-validation.

Results: We identified 1049 cases where a virus was the only etiology, and developed predictive models against 2317 cases where the etiology was known but non-viral (bacterial, protozoal, or mixed). Variables predictive of a viral etiology included lower age, a dry and cold season, increased height-for-age z-score (HAZ), lack of bloody diarrhea, and presence of vomiting. Cross-validation suggests an AUC of 0.825 can be achieved with a parsimonious model of 5 variables, achieving a specificity of 0.85, a sensitivity of 0.59, a NPV of 0.82 and a PPV of 0.64.

Conclusion: Predictors of the etiology of pediatric diarrhea can be used by providers in low-resource settings to inform clinical decision-making. The use of non-laboratory methods to diagnose viral causes of diarrhea could be a step towards reducing inappropriate antibiotic prescription worldwide.
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http://dx.doi.org/10.1371/journal.pntd.0008677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7588112PMC
October 2020

Diabetes, Body Fatness, and Insulin Prescription Among Adolescents and Young Adults with Cancer.

J Adolesc Young Adult Oncol 2021 04 29;10(2):217-225. Epub 2020 Jul 29.

Huntsman Cancer Institute, Salt Lake City, Utah, USA.

Rates of obesity and obesity-related health consequences, including type 2 diabetes (T2D) and cancer, continue to rise. While cancer patients are at an increased risk of developing T2D, the prevalence of T2D and insulin prescription among young patients with cancer remains unknown. Using the Total Cancer Care Study cohort at Huntsman Cancer Institute (Salt Lake City, UT), we identified individuals age 18-39 years at cancer diagnosis between 2009 and 2019. Multivariable logistic regression was used to investigate associations between body mass index (BMI) with insulin prescription within 1 year of cancer diagnosis. In total, 344 adolescents and young adults (AYAs) were diagnosed with primary invasive cancer. Within this cohort, 19 patients (5.5%) were ever diagnosed with T2D, 48 AYAs ever received an insulin prescription (14.0%), and 197 were overweight or obese (BMI: 25+ kg/m) at cancer diagnosis. Each kg/m unit increase in BMI was associated with 6% increased odds of first insulin prescription within 1 year of cancer diagnosis among AYAs, even after adjustment for age, sex, smoking history, marital status, glucocorticoid prescription, and cancer treatments (odds ratio = 1.06, 95% confidence interval 1.02-1.11;  = 0.005). One in every 18 AYAs with cancer ever had T2D, 1 in 7 AYA patients with cancer ever received an insulin prescription, and higher BMI was associated with increased risk of insulin prescription within a year of cancer diagnosis among AYAs. Understanding the incidence of T2D and insulin prescription/use is critical for short-term and long-term clinical management of AYAs with cancer.
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http://dx.doi.org/10.1089/jayao.2020.0071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064923PMC
April 2021

Higher Ultraviolet Radiation Exposure Among Rural-Dwelling Versus Urban-Dwelling Adults and Children: Implications for Skin Cancer Prevention.

J Community Health 2021 02;46(1):147-155

Huntsman Cancer Institute, 2000 Circle of Hope, Salt Lake City, UT, 84112, USA.

Ultraviolet radiation (UVR) exposure is a primary risk factor for the development of melanoma. However, adults and adolescents often do not engage in preventive behaviors to reduce UVR exposure. Rural residents may be at higher risk for melanoma due to lower use of sun protection strategies, which increases their overall UVR exposure compared to those who live in urban areas. The purpose of this study was to evaluate differences in UVR exposure between rural and urban residents in a geographic area with high incidence of melanoma. Children (aged 8-17 years) and adults (≥ 18 years) from rural and urban areas of Utah were asked to wear a UVR monitoring device for 14 days. The sample included 97 children and 97 adults. Data was collected from June to October 2018. Non-parametric Mann-Whitney tests and quantile regression were used to compare UVR exposure levels between urban and rural participants, separately for adults and children. For adults, rural residence significantly increased total UVR dose ( β: 24.6; 95% CI 3.75, 42.74) and the UVR dose during peak UVR hours among participants with the highest UVR doses (β: 16.3; 95% CI 17.4, 24.63). Rural children exhibited significantly higher UVR doses for peak UVR hours for the entire study period (β: 4.14; 95% CI 0.83, 7.46) and on weekdays (β: 0.39; 95% CI 0.05, 0.73). The findings from this study indicate that rural residents may receive higher levels of UVR exposure than urban residents, and that prevention efforts could be tailored to address these geographical differences.
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http://dx.doi.org/10.1007/s10900-020-00860-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736287PMC
February 2021

Factors associated with appropriate and low-value PSA testing.

Cancer Epidemiol 2020 06 8;66:101724. Epub 2020 May 8.

Huntsman Cancer Institute and University of Utah, Salt Lake City, UT, USA. Electronic address:

Background: Prostate-specific antigen (PSA) testing for early detection of prostate cancer is low-value when it is not indicated by guidelines and the harms outweigh the benefits. In this retrospective cohort study, we identify provider and patient factors associated with PSA testing, particularly in situations where testing would be low-value.

Methods: We used electronic health record data from 2011 to 2018 representing 1,738,021 health system encounters in the United States. Using logistic generalized estimating equation models, we examined patient factors (age, comorbid illness, family history, race and prior PSA results), provider factors (gender, specialty, graduation year and medical school rank), and overall time trends associated with PSA testing in low-value and appropriate settings.

Results: Comorbid illness (odds ratio (OR) 0.0 for 3+ conditions vs none) and no prior PSA testing (OR 0.2) were associated with a lower likelihood of PSA testing in low-value situations, while family history of prostate cancer (OR 1.6) and high prior PSA test results (OR 2.2 for PSA > 6 vs 0-1) were associated with a greater likelihood. Men aged 55-65 years were at greatest risk for PSA testing in low-value situations. The provider factor associated with PSA testing in low-value situations was specialty, with urologists being most likely (OR 2.3 versus advanced practice providers). Internal medicine physicians were more likely to perform PSA testing during low-value situations (OR 1.3 versus advanced practice providers) but much more likely to order a PSA test where appropriate (OR 2.2). All PSA testing decreased since 2011.

Conclusion: We identified several patient and provider factors associated with PSA testing in low-value settings. Some aspects suggest attention to relevant factors for PSA testing in low-value settings (e.g. comorbid illness), while others may encourage PSA testing in low-value settings (e.g. family history). The greatest likelihood of PSA testing in low-value settings is among men within the age range most commonly recommended by guidelines.
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Source
http://dx.doi.org/10.1016/j.canep.2020.101724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275910PMC
June 2020
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