Colorado Multiple Institutional Review Board Research Articles

Motivational Interviewing for Maternal Immunisation (MI4MI) study: a protocol for an implementation study of a clinician vaccine communication intervention for prenatal care settings

IntroductionVaccination against influenza and pertussis in pregnancy offers a ‘two-for-one’ opportunity to protect mother and child. Pregnant patients have increased risk of severe disease from influenza and newborns have increased...

‘Presumptively Initiating Vaccines and Optimizing Talk with Motivational Interviewing’ (PIVOT with MI) trial: a protocol for a cluster randomised controlled trial of a clinician vaccine communication intervention

IntroductionA key contributor to underimmunisation is parental refusal or delay of vaccines due to vaccine concerns. Many clinicians lack confidence in communicating with vaccine-hesitant parents (VHP) and perceive that their...

A Framework for the Systematic Evaluation of Anatomy Education Apps

BackgroundMobile‐based applications (Apps) are one of the fastest growing trends in educational technology. A search on the iTunes App Store, for example, results in 142 Apps in response to the search term “anatomy”. However, most educational Apps are not peer‐reviewed. The quality and accuracy are suspect, and few have been evaluated in the classroom. A comprehensive resource that provides guidance as to the educational usefulness, quality, and content accuracy of Apps in the anatomical sciences is needed.Aims To triangulate existing educational technology frameworks into a framework for evaluating anatomy education Apps With a national sample of academic technology leads, faculty and students, test and validate the framework MethodsPhase 1 triangulated peer‐reviewed articles on Apps, with known educational technology frameworks from the literature (Hanrahan et al., 2014; Liu et al., 2010; Romrell et al., 2014; Ruiz et al., 2006; Van Nuland et al., 2017). Phase 2 validated the framework in two steps. Phase 2A used chain referral sampling (i.e. n = 6 with at least one educational technology lead from each of the four AAMC regions: East, West, South, and Central) to obtain feedback. In Phase 2B, participants were recruited from Anatomy Connected Open Forum and through chain referral sampling (n = 58 agreed to participate). Participants applied the revised framework to two anatomy apps (Complete Anatomy and Heart Pro III) and completed a content validity survey. All methods were approved by the Colorado Multiple Institutional Review Board.ResultsPhase 1 resulted in the formation of a framework that was revised in Phase 2a and is hosted here https://docs.google.com/forms/d/1s5VWA1OfE‐HGNLz_LezMb3ngofPztRaOb7PFCXl_jjc/viewform?edit_requested=true. A total of 25 participants (14 faculty, 4 tech leads and 7 students) fulfilled all parts of Phase 2b to completion. Content validity was analyzed using Lawshe's content validity ratio; critical values (>0.39 as determined by Wilson et al., 2012) with 0.05 significance for two‐tailed test were achieved with 11 of the 26 criteria, including usability, organization, reliability, navigation, self‐assessment, content breadth, content depth, content accuracy, multimedia accuracy, recommendation for others, and overall value.Discussion and ConclusionAnatomy Education App framework validation presents a major asset for students, faculty and administrators based on feedback from a national panel; the framework is freely available. The validation is limited by the low number of respondents, but will be enhanced as more investigators apply the framework to their research.Support or Funding InformationRymer Small Grants Program, Academy of Medical Educators, University of Colorado School of MedicineThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Impact of Deep Brain Stimulation of the Subthalamic Nucleus on Neuropsychological Outcomes and Voxel‐Based‐Morphometric‐Analyses in Parkinson's Disease Patients

Parkinson's Disease (PD) is a movement disorder that is characterized by tremor, rigidity, and bradykinesia, due to significant cell‐death of the dopaminergic neurons in the substantia nigra. Deep brain stimulation (DBS) is a surgical intervention used to treat PD patients in which stimulating electrodes are placed bilaterally, most often in the subthalamic nucleus (STN). STN‐DBS is restricted to those who respond sufficiently well to a dopaminergic medication regimen. This procedure alleviates the motor symptoms associated with PD. Historically, the majority of clinical research on STN‐DBS has focused on motor outcomes. Until recently, few studies had explored the effect of STN‐DBS on post‐surgical cognitive and memory outcomes. Moreover, the relationship between cognitive outcomes and neuroanatomical changes in PD patients with STN‐DBS is largely unknown. The goal of this study was to correlate pre‐ and post‐ surgical memory and cognitive neuropsychological outcomes with volumetric changes in relevant neuroanatomical structures before and after DBS intervention. Thus far, 11 PD patients met inclusion criteria for this Colorado Multiple Institutional Review Board (COMIRB) approved study (COMIRB 16‐1060). Voxel‐based‐morphometry of cortical and subcortical brain regions were used to assess structural changes in T1‐weighted MR. Analyzed neuropsychological measures include those from the second edition of the California Verbal Language Test (CVLT‐II). Preliminary neuropsychological analyses suggest that Standard CVLT‐II Long Delayed Free recall of List Learning decreases post surgically. Further neuropsychological and neuroanatomical analyses are ongoing. This study is relevant because it will better characterize neuroanatomical and neurofunctional changes that occur with STN‐DBS so that physicians are better prepared to support their patients after STN‐DBS. Eventually, studies like this one may lead to predictive measures which allow physicians to better screen for patients who will benefit most from DBS surgery based on neuropsychological pre‐testing.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Clinical Characteristics of Enterovirus A71 Neurologic Disease During an Outbreak in Children in Colorado, 2018

Background: In May 2018, Children's Hospital Colorado (CHCO) noted an outbreak of enterovirus (EV) A71-associated neurologic disease. Methods: A case of EV-associated neurologic disease was defined as any child presenting to CHCO with meningitis, encephalitis, acute flaccid myelitis (AFM), and/or seizures between March 1 and November 30, 2018 with an EV detected from a biologic specimen. EV-A71 cases were compared to other EV cases during the same period. EV-A71-associated AFM cases were also compared to EV-D68-associated AFM cases from 2013-2018. Findings: Of seventy-four children with EV-associated neurologic disease, forty-three (58%) were EV-A71-associated. Median age of EV-A71 cases was 22.7 months (IQR: 4-31.9 months); 34 (79%) were male. Neurologic involvement in EV-A71 cases included meningitis (93%), encephalitis (72%), and AFM (23%). All EV-A71 cases had fever; eighteen (42%) had hand, foot, or mouth (HFM) lesions. Neurologic findings distinguishing EV-A71-associated cases from other EV-associated cases (n=31) included myoclonus (60% vs. 16%, p<0.0001), ataxia (58% vs. 16%, p=0.003), weakness (30% vs. 6%, p=0.012), and autonomic instability (47% vs. 10%, p<0.0001). Amongst specimens collected from EV-A71 cases, EV-A71 was detected in 94% of rectal, 79% of oropharyngeal, 56% of nasopharyngeal, and 20% of cerebrospinal fluid specimens. Overall, 91% of children with EV-A71-associated neurologic disease fully recovered. Compared to EV-D68-associated AFM cases (n=8), EV-A71-associated AFM cases (n=10) were younger (19 vs. 100 months, p=0.034) with earlier neurologic onset after prodromal illness (median 1 vs. 5.5 days, p=0.011). HFM lesions were only present in EV-A71-associated AFM cases (60%), whereas preceding respiratory symptoms were more uniformly noted with EV-D68. EV-A71-associated AFM cases had milder weakness, more rapid improvement and were more likely to completely recover (90% vs. 13%, p=0.0029). Interpretation: This outbreak of EV-A71 neurologic disease, the largest reported in the Western hemisphere, was characterized by fever, myoclonus, ataxia, weakness, autonomic instability, and full recovery in the majority. Testing of non-sterile site specimens was key to case and outbreak identification. Funding Statement: KM receives funding through NIH/NIAID grant K23AI28069. RM receives funding through the Pediatric Epilepsy Research Consortium and West Pharmaceuticals, Inc. CP receives funding from C.R. Bard. TS receives private donor funding. Colorado Department of Public Health and Environment receives funding through Centers for Disease Control and Prevention grant CK14-1401. Declaration of Interests: The authors report no conflicts of interest. Ethics Approval Statement: Research and data collection protocols were approved by the Colorado Multiple Institutional Review Board with waiver of informed consent.

Assessment of achieved systolic blood pressure in newly treated hypertensive patients aged 60-79 years before and after Eighth Joint National Committee recommendations.

To determine whether patients who were newly prescribed antihypertensive therapy after the Eighth Joint National Committee (JNC 8) update were treated to a relaxed systolic blood pressure (SBP) goal compared with patients treated before the update. A retrospective cohort study approved by the Colorado Multiple Institutional Review Board. Patients aged 60-79 years, without diabetes or chronic kidney disease (CKD), newly treated for hypertension at a University of Colorado primary care clinics were included. The mean first-achieved and last-stable SBPs of patients newly prescribed antihypertensive medications from 1 January 2012 to 31 December 31 2013 (before cohort) were compared with patients newly prescribed antihypertensive therapy from 1 January 2014 to 1 October 2015 (after cohort). The mean number of antihypertensive medications at first-achieved SBP, the time to first-achieved SBP, and the class of initial antihypertensive medications were also evaluated. A total of 128 patients were included, 64 patients in each cohort. The coprimary outcome of first-achieved mean SBP did not differ between the groups (131.3 mmHg versus 130.2 mmHg; p = 0.65). Last-stable mean SBP values were also similar between the groups (130.2 mmHg versus 129.5 mmHg; p = 0.74). Angiotensin converting enzyme inhibitors (ACE-I) were the most frequently initiated antihypertensive agent in both cohorts (43.8% versus 48.4%; p = 0.72). Our findings suggest that the JNC 8 recommendations did not alter SBP goals among patients aged 60-79 years newly treated for hypertension at University of Colorado primary care clinics.

Cortical physiology as a therapeutic target in Parkinson′s disease related dementia and cognitive dysfunction: study protocol for a randomized controlled trial

Background: Dementia is the leading cause of nursing home placement in Parkinson's disease (PD), yet little is known about the causes of cognitive dysfunction in PD and there are no effective treatments. Our preliminary data and other published studies suggest that abnormalities in brain activity involving networks important for normal thinking and memory may contribute to cognitive dysfunction in PD and may represent a target for treatment. Methods/Design: A randomized control trial will be conducted to assess the therapeutic potential of bifrontal repetitive transcranial magnetic stimulation (rTMS) in modulating cortical activity related to cognitive dysfunction in PD. This study will be performed at the University of Colorado Denver, Anschutz Campus, in Aurora, Colorado. Fifty-five PD patients (> 40 years of age) with mild cognitive impairment or mild dementia will be included and randomized in a 1:1 ratio to sham or real rTMS groups. Primary outcome measurement is the total score of the Mattis Dementia Rating Scale. Secondary outcome measurements are domain specific ratings of executive function, memory, language, attention, and visuospatial abilities. Discussion: If bifrontal rTMS results in positive changes to cognitive function in PD patients with mild cognitive impairment, this may represent a new and effective treatment for PD-related cognitive dysfunction. Secondly, evaluation of any bifrontal rTMS-induced changes to cognitive function will improve the current understanding of the mechanisms behind the causes of cognitive dysfunction in PD. Trial registration: Clinical Trials.gov identifier: NCT02346708; registered on 9 January 2015. Ethics: This study protocol was approved by the Colorado Multiple Institutional Review Board (COMIRB) (approval No. 13-2474) and will be performed in accordance with the Declaration of Helsinki. Informed consent: Signed informed consent will be obtained from the patients or their guardians.

Evaluation of Statin Prescribing for Secondary Prevention in Primary Care Following New Guideline Recommendations.

The American College of Cardiology/American Heart Association (ACC/AHA) Guideline on the Treatment of Blood Cholesterol recommends high-intensity statin therapy for most patients with established atherosclerotic cardiovascular disease (ASCVD) versus previously recommended low-density lipoprotein cholesterol targets. The impact of the ACC/AHA guidelines on prescribing patterns in primary care is uncertain. To describe the prescribing habits of statin therapy in primary care patients with ASCVD before and after the ACC/AHA guidelines were published. This retrospective observational study evaluated patients with ASCVD who were seen in at least 1 of 8 primary care clinics in the University of Colorado Health system. It received expedited approval by the Colorado Multiple Institutional Review Board. The primary outcome measure was the proportion of patients with established ASCVD prescribed high-intensity statin therapy within 1 year before or after guideline release. In total, 220 patients were included in the analysis with 110 in the before and 110 in the after cohort. For the primary outcome analysis, the rate of high-intensity statin utilization in the before versus after groups was significantly greater (25.5% vs 41.8%, P = 0.01). For ages 76 to 89 years, 36 of 37 and 29 of 30 patients in the before and after groups were receiving moderate- to high-intensity statin therapy (97.3% vs 96.7%, P = 0.99). Subgroup analysis in the after cohort for all ages showed no change in statin therapy for 77% of patients. High-intensity statin prescribing increased in patients with ASCVD after release of the ACC/AHA cholesterol guidelines. Our data indicate that national evidence-based guidelines may influence clinical practice in very high risk patients.

Abstract 196: Heart and Lung Transplant Center Policies on Recreational and Medical Marijuana Use

Introduction: As of January 2013, medical marijuana (MM) is currently legal in 18 states across the United States. In thoracic transplantation, standardized polices do not exist regarding MM use. We surveyed 317 US thoracic transplant medical directors regarding their center’s policies surrounding both MM and recreational marijuana (RM) use. Methods: We obtained names of the medical directors for US heart and lung transplant centers through the United Network for Organ Sharing (UNOS). A survey regarding MM and RM policies was developed, approved by the Colorado Multiple Institutional Review Board, and emailed through SurveyMonkey from April 2012-October 2012. Descriptive statistics were used to determine overall percentage of responses. Results: The survey was sent to 317 directors; 82 surveys were returned (25.8% overall response). 67.1%, 28.0%, and 4.9% were from heart, lung, and heart-lung programs, respectively. 80.5% of respondents were directors of adult programs, while 12.2% were from pediatric programs and 7.3% were affiliated with both adult and pediatric programs. Table 1 summarizes center policies on contraindications. During the study period, MM was state legalized for 32.9% of the directors. 2.5% of programs allowed their patients to drive while using MM, 21.0% did not, and 33.3% had no policy regarding this subject. Only 5.0% of respondents believed that a drug-drug interaction existed between marijuana and a patient’s immunosuppressive medications, while 78.8% were unsure of an drug-drug interactions. Conclusions: There is substantial heterogeneity among thoracic transplant programs about the acceptability of both MM and RM as a contraindication for transplantation. Additional data about drug-drug interactions with marijuana and the influence of MM and RM on transplant outcomes is warranted; harmonization of state and federal laws would advance this agenda.

A Novel, In-solution Separation of Endogenous Cardiac Sarcomeric Proteins and Identification of Distinct Charged Variants of Regulatory Light Chain

The molecular conformation of the cardiac myosin motor is modulated by intermolecular interactions among the heavy chain, the light chains, myosin binding protein-C, and titin and is governed by post-translational modifications (PTMs). In-gel digestion followed by LC/MS/MS has classically been applied to identify cardiac sarcomeric PTMs; however, this approach is limited by protein size, pI, and difficulties in peptide extraction. We report a solution-based work flow for global separation of endogenous cardiac sarcomeric proteins with a focus on the regulatory light chain (RLC) in which specific sites of phosphorylation have been unclear. Subcellular fractionation followed by OFFGEL electrophoresis resulted in isolation of endogenous charge variants of sarcomeric proteins, including regulatory and essential light chains, myosin heavy chain, and myosin-binding protein-C of the thick filament. Further purification of RLC using reverse-phase HPLC separation and UV detection enriched for RLC PTMs at the intact protein level and provided a stoichiometric and quantitative assessment of endogenous RLC charge variants. Digestion and subsequent LC/MS/MS unequivocally identified that the endogenous charge variants of cardiac RLC focused in unique OFFGEL electrophoresis fractions were unphosphorylated (78.8%), singly phosphorylated (18.1%), and doubly phosphorylated (3.1%) RLC. The novel aspects of this study are that 1) milligram amounts of endogenous cardiac sarcomeric subproteome were focused with resolution comparable with two-dimensional electrophoresis, 2) separation and quantification of post-translationally modified variants were achieved at the intact protein level, 3) separation of intact high molecular weight thick filament proteins was achieved in solution, and 4) endogenous charge variants of RLC were separated; a novel doubly phosphorylated form was identified in mouse, and singly phosphorylated, singly deamidated, and deamidated/phosphorylated forms were identified and quantified in human non-failing and failing heart samples, thus demonstrating the clinical utility of the method.

Colonoscopy Completion in a Large Safety Net Health Care System

Anecdotally, patients in safety net health care systems have difficulty completing screening and diagnostic colonoscopies, but this is poorly characterized. It is important to understand this phenomenon to improve low rates of colorectal cancer screening in vulnerable populations and to ensure that patients with signs and symptoms complete medically indicated colonoscopic evaluations. We performed a 6-month retrospective review of outpatient endoscopy laboratory scheduling and procedure logs and electronic medical records at Denver Health Medical Center (DHMC), a large safety net health care system, to describe rates and sociodemographic predictors of colonoscopy nonattendance and inadequate (fair/poor) bowel preparation. Predictor variables included patient age, gender, race/ethnicity, procedure indication, and insurance type. The nonattendance rate was 41.7% for all scheduled outpatient colonoscopies without difference between screening and diagnostic procedures. Consistent with non-safety net systems, the rate of inadequate bowel preparation was 30.2%; however, the rate of poor bowel preparation that absolutely precluded an exam was 9.9%. Correctional care patients had markedly higher rates of nonattendance and inadequate bowel preparation compared with other groups. A very large proportion of patients scheduled for colonoscopy in a large safety net health care system do not attend their procedures, and among those who do, there is a high rate of inadequate bowel preparation leading to incomplete and aborted evaluations. Interventions are needed to promote the more efficient use of a limited and expensive resource and to achieve higher rates of screening and medically indicated diagnostic colonoscopies in vulnerable patient populations.

Performance on the Mini-Mental State Examination and Mattis Dementia Rating Scale Among Older American Indians

Performance on the Mini-Mental State Examination and Mattis Dementia Rating Scale Among Older American Indians

Current management of ventricular septal defect

At this time, the current practice for treatment of patients with isolated ventricular septal defect is infrequently studied. With this in mind, it was our intent to assess the current management of ventricular septal defect at a single center, The Children's Hospital, Denver. We reviewed the practice at this institution to determine if there is an evidence base for when or if a patient with an isolated ventricular septal defect requires surgical repair. With approval from the Colorado Multiple Institutional Review Board (protocol # 06-0097), we reviewed the data on patients with isolated ventricular septal defect seen during the calendar years of 2004 and 2005, determining the state of the patients, and the level of intervention through December 31, 2005.

Deuterium dilution: the time course of 2H enrichment in saliva, urine, and serum.

Total body water (TBW) volume can by measured in humans by administering an oral dose of an isotope tracer, such as 2H2O or H218O, and measuring the isotope enrichment in saliva, urine, or serum samples. Although serum has long been considered the medium of choice for measuring isotope enrichment because of rapid tracer equilibration (1), urine or saliva sampling is less burdensome to the patient. However, the measurement of isotope enrichment was found to be less reliable in urine than in serum, possibly because of a longer time period for isotopic equilibration of the bladder contents relative to serum (2). Schoeller et al. (1) suggested that saliva was an acceptable medium for measurement of TBW using 2H218O because isotopic equilibration occurred within 3 h and provided results similar to those obtained in serum. In another study, the enrichments of 2H in saliva and plasma were identical and reached a plateau 2 h after administration of an oral 10-g dose of 2H2O (3). To our knowledge, there have been no within-subject comparisons of the time to achieve a 2H enrichment plateau in saliva, urine, and serum samples obtained simultaneously. The purpose of this study, therefore, was to determine the time course for isotope equilibration of 2H in saliva, urine, and serum and the level of agreement in 2H enrichment among these media. This information can be applied to protocols for measurement of TBW in clinical and research settings (4)(5). Five healthy, weight-stable, nonobese women [mean (SD) body mass index, 22.1 (2.0) kg/m2], 20 to 43 years of age, provided written informed consent and completed the study. The study was approved by the Colorado Multiple Institutional Review Board. The …