Update of a Multivariable Opioid Overdose Risk Prediction Model to Enhance Clinical Care for Long-term Opioid Therapy Patients.

BACKGROUND: Clinical opioid overdose risk prediction models can be useful tools to reduce the risk of overdose in patients prescribed long-term opioid therapy (LTOT). However, evolving overdose risk environments and clinical practices in addition to potential harmful model misapplications require careful assessment prior to widespread implementation into clinical care. Models may need to be tailored to meet local clinical operational needs and intended applications in practice. OBJECTIVE: To update and validate an existing opioid overdose risk model, the Kaiser Permanente Colorado Opioid Overdose (KPCOOR) Model, in patients prescribed LTOT for implementation in clinical care. DESIGN, SETTING, AND PARTICIPANTS: The retrospective cohort study consisted of 33, 625 patients prescribed LTOT between January 2015 and June 2019 at Kaiser Permanente Colorado, with follow-up through June 2021. MAIN MEASURES: The outcome consisted of fatal opioid overdoses identified from vital records and non-fatal opioid overdoses from emergency department and inpatient settings. Predictors included demographics, medication dispensings, substance use disorder history, mental health history, and medical diagnoses. Cox proportional hazards regressions were used to model 2-year overdose risk. KEY RESULTS: During follow-up, 65 incident opioid overdoses were observed (111.4 overdoses per 100,000 person-years) in the study cohort, of which 11 were fatal. The optimal risk model needed to risk-stratify patients and to be easily interpreted by clinicians. The original 5-variable model re-validated on the new study cohort had a bootstrap-corrected C-statistic of 0.73 (95% CI, 0.64-0.85) compared to a C-statistic of 0.80 (95% CI, 0.70-0.88) in the updated model and 0.77 (95% CI, 0.66-0.87) in the final adapted 7-variable model, which was also well-calibrated. CONCLUSIONS: Updating and adapting predictors for opioid overdose in the KPCOOR Model with input from clinical partners resulted in a parsimonious and clinically relevant model that was poised for integration in clinical care.

Equitable implementation of S.A.F.E. Firearm: A multi-method pilot study.

Attention to health equity is critical in the implementation of firearm safety efforts. We present our operationalization of equity-oriented recommendations in preparation for launch of a hybrid effectiveness-implementation trial focused on firearm safety promotion in pediatric primary care as a universal suicide prevention strategy. In Step 1 of our process, pre-trial engagement with clinican partners and literature review alerted us that delivery of a firearm safety program may vary by patients' medical complexity, race, and ethnicity. In Step 2, we selected the Health Equity Implementation Framework to inform our understanding of contextual determinants (i.e., barriers and facilitators). In Step 3, we leveraged an implementation pilot across 5 pediatric primary care clinics in 2 health system sites to study signals of inequities. Eligible well-child visits for 694 patients and 47 clinicians were included. Our results suggested that medical complexity was not associated with program delivery. We did see potential signals of inequities by race and ethnicity but must interpret with caution. Though we did not initially plan to examine differences by sex assigned at birth, we discovered that clinicians may be more likely to deliver the program to parents of male than female patients. Seven qualitative interviews with clinicians provided additional context. In Step 4, we interrogated equity considerations (e.g., why and how do these inequities exist). In Step 5, we will develop a plan to probe potential inequities related to race, ethnicity, and sex in the fully powered trial. Our process highlights that prospective, rigorous, exploratory work is vital for equity-informed implementation trials.

Teaching meiosis with the DNA triangle framework: A classroom activity that changes how students think about chromosomes.

Many biology students struggle to learn about the process of meiosis and have particular difficulty understanding the molecular basis of crossing over and the importance of homologous pairing for proper segregation. To help students overcome these challenges, we designed an activity that uses a newly developed Chromosome Connections Kit® from 3-D Molecular Designs to allow learners to explore meiosis at the molecular level. We took a backwards design approach in constructing an effective classroom activity. We developed evidence-based learning objectives and designed a crossing over activity that targets students' misconceptions and key concepts about meiosis. Assessment questions were designed based on the learning objectives and common student misconceptions. The activity consists of three parts: an interactive introductory video, a model-based activity, and reflection questions. The activity was first beta-tested with a small number of students and revised based on feedback. The revised activity was deployed in a mid-level Cell and Molecular Biology course. Analysis of pre-/post-assessment data from students who completed the activity (n = 83) showed strong learning gains on concepts related to ploidy, homology, segregation, and the mechanism and purpose of crossing over. Additionally, students who participated in the activity outperformed nonparticipants on a Genetics assessment about meiosis the following semester.

In her own words: understanding the health needs of older lesbians.

This project illuminates the unique struggles and barriers lesbians face. A community advisory board (CAB) was developed and 31 in-depth interviews were conducted with lesbians aged 56-84 in the Rocky Mountain region. Interviews were audio recorded, transcribed, and coded using critical discourse analysis. Themes included: a culture of identity-hiding; lack of recognition and discrimination in health care; channeling passion, fear, and anger into action; concerns about aging; and identified health needs and opportunities. There is a need for innovative and equitable services that understand the barriers and struggles that older lesbian adults face so they can receive high-quality care.

Study protocol for a type III hybrid effectiveness-implementation trial of strategies to implement firearm safety promotion as a universal suicide prevention strategy in pediatric primary care.

BACKGROUND: Insights from behavioral economics, or how individuals' decisions and behaviors are shaped by finite cognitive resources (e.g., time, attention) and mental heuristics, have been underutilized in efforts to increase the use of evidence-based practices in implementation science. Using the example of firearm safety promotion in pediatric primary care, which addresses an evidence-to-practice gap in universal suicide prevention, we aim to determine: is a less costly and more scalable behavioral economic-informed implementation strategy (i.e., "Nudge") powerful enough to change clinician behavior or is a more intensive and expensive facilitation strategy needed to overcome implementation barriers? METHODS: The Adolescent and child Suicide Prevention in Routine clinical Encounters (ASPIRE) hybrid type III effectiveness-implementation trial uses a longitudinal cluster randomized design. We will test the comparative effectiveness of two implementation strategies to support clinicians' use of an evidence-based firearm safety practice, S.A.F.E. Firearm, in 32 pediatric practices across two health systems. All pediatric practices in the two health systems will receive S.A.F.E. Firearm materials, including training and cable locks. Half of the practices (k = 16) will be randomized to receive Nudge; the other half (k = 16) will be randomized to receive Nudge plus 1 year of facilitation to target additional practice and clinician implementation barriers (Nudge+). The primary implementation outcome is parent-reported clinician fidelity to the S.A.F.E Firearm program. Secondary implementation outcomes include reach and cost. To understand how the implementation strategies work, the primary mechanism to be tested is practice adaptive reserve, a self-report practice-level measure that includes relationship infrastructure, facilitative leadership, sense-making, teamwork, work environment, and culture of learning. DISCUSSION: The ASPIRE trial will integrate implementation science and behavioral economic approaches to advance our understanding of methods for implementing evidence-based firearm safety promotion practices in pediatric primary care. The study answers a question at the heart of many practice change efforts: which strategies are sufficient to support change, and why? Results of the trial will offer valuable insights into how best to implement evidence-based practices that address sensitive health matters in pediatric primary care. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04844021 . Registered 14 April 2021.

Designing a Primary Care-Based Deprescribing Intervention for Patients with Dementia and Multiple Chronic Conditions: a Qualitative Study.

BACKGROUND: Patients with dementia and multiple chronic conditions (MCC) frequently experience polypharmacy, increasing their risk of adverse drug events. OBJECTIVES: To elucidate patient, family, and physician perspectives on medication discontinuation and recommended language for deprescribing discussions in order to inform an intervention to increase awareness of deprescribing among individuals with dementia and MCC, family caregivers and primary care physicians. We also explored participant views on culturally competent approaches to deprescribing. DESIGN: Qualitative approach based on semi-structured interviews with patients, caregivers, and physicians. PARTICIPANTS: Patients aged ≥ 65 years with claims-based diagnosis of dementia, ≥ 1 additional chronic condition, and ≥ 5 chronic medications were recruited from an integrated delivery system in Colorado and an academic medical center in Maryland. We included caregivers when present or if patients were unable to participate due to severe cognitive impairment. Physicians were recruited within the same systems and through snowball sampling, targeting areas with large African American and Hispanic populations. APPROACH: We used constant comparison to identify and compare themes between patients, caregivers, and physicians. KEY RESULTS: We conducted interviews with 17 patients, 16 caregivers, and 16 physicians. All groups said it was important to earn trust before deprescribing, frame deprescribing as routine and positive, align deprescribing with goals of dementia care, and respect caregivers' expertise. As in other areas of medicine, racial, ethnic, and language concordance was important to patients and caregivers from minority cultural backgrounds. Participants favored direct-to-patient educational materials, support from pharmacists and other team members, and close follow-up during deprescribing. Patients and caregivers favored language that explained deprescribing in terms of altered physiology with aging. Physicians desired communication tips addressing specific clinical situations. CONCLUSIONS: Culturally sensitive communication within a trusted patient-physician relationship supplemented by pharmacists, and language tailored to specific clinical situations may support deprescribing in primary care for patients with dementia and MCC.

Latino Parents' Perceptions of Pediatric Weight Counseling Terms.

OBJECTIVE: Little is known about Latino parents' perceptions of weight-related language in English or Spanish, particularly for counseling obese youth. We sought to identify English and Spanish weight counseling terms perceived by Latino parents across demographic groups as desirable for providers to use, motivating, and inoffensive. METHODS: Latino parents of children treated at urban safety-net clinics completed surveys in English or Spanish. Parents rated the desirable, motivating, or offensive properties of terms for excess weight using a 5-point scale. We compared parental ratings of terms and investigated the association of parent and child characteristics with parent perceptions of terms. RESULTS: A total of 525 surveys met inclusion criteria (255 English, 270 Spanish). English survey respondents rated "unhealthy weight" and "too much weight for his/her health" the most motivating and among the most desirable and least offensive terms. Spanish survey respondents found "demasiado peso para su salud" highly desirable, highly motivating, and inoffensive, and respondents valued its connection to the child's health. Commonly used clinical terms "overweight"/"sobrepeso" and "high BMI [body mass index]"/"índice de masa corporal alta" were not as desirable or as motivating. "Chubby," "fat," "gordo," and "muy gordo" were the least motivating and most offensive terms. Parents' ratings of commonly used clinical terms varied widely across demographic groups, but more desirable terms had less variability. CONCLUSIONS: "Unhealthy weight," "too much weight for his/her health," and its Spanish equivalent, "demasiado peso para su salud," were the most desirable and motivating, and the least offensive terms. Latino parents' positive perceptions of these terms occurred across parent and child characteristics, supporting their use in weight counseling.

Lessons learned from community-based participatory research: establishing a partnership to support lesbian, gay, bisexual and transgender ageing in place.

Background: Due to a history of oppression and lack of culturally competent services, lesbian, gay, bisexual and transgender (LGBT) seniors experience barriers to accessing social services. Tailoring an evidence-based ageing in place intervention to address the unique needs of LGBT seniors may decrease the isolation often faced by this population. Objective: To describe practices used in the formation of a community-based participatory research (CBPR), partnership involving social workers, health services providers, researchers and community members who engaged to establish a LGBT ageing in place model called Seniors Using Supports To Age In Neighborhoods (SUSTAIN). Methods: A case study approach was employed to describe the partnership development process by reflecting on past meeting minutes, progress reports and interviews with SUSTAIN's partners. Results: Key partnering practices utilized by SUSTAIN included (i) development of a shared commitment and vision; (ii) identifying partners with intersecting spheres of influence in multiple communities of identity (ageing services, LGBT, health research); (iii) attending to power dynamics (e.g. equitable sharing of funds); and (iv) building community capacity through reciprocal learning. Although the partnership dissolved after 4 years, it served as a successful catalyst to establish community programming to support ageing in place for LGBT seniors. Conclusion: Multi-sector stakeholder involvement with capacity to connect communities and use frameworks that formalize equity was key to establishing a high-trust CBPR partnership. However, lack of focus on external forces impacting each partner (e.g. individual organizational strategic planning, community funding agency perspectives) ultimately led to dissolution of the SUSTAIN partnership even though implementation of community programming was realized.

Perspectives of LGBTQ Older Adults on Aging in Place: A Qualitative Investigation.

This qualitative study conducted by a community-research partnership used multiple types of data collection to examine variables relevant for LGBTQ older adults who wished to age in place in their urban Denver neighborhood. Focus groups, interviews, and a town hall meeting were used to identify barriers and supports to aging in place. Participants (N = 73) identified primarily as lesbian or gay, aged 50-69, and lived with a partner. Ageism, heterosexism, and cisgenderism emerged as cross-cutting themes that negatively impact access to health care, housing, social support, home assistance, and legal services. Resilience from weathering a lifetime of discrimination was identified as a strength to handle aging challenges. Recommendations for establishing an aging in place model included establishing welcoming communities and resource centers and increasing cultural competence of service providers. This study provides a unique contribution to understanding the psychosocial, medical, and legal barriers for successfully aging in place.

High-Efficiency Gene Transfection of Cells through Carbon Nanotube Arrays.

Introducing nucleic acids into mammalian cells is a crucial step to elucidate biochemical pathways, and to modify gene expression and cellular development in immortalized cells, primary cells, and stem cells. Current transfection technologies are time consuming and limited by the size of genetic cargo, the inefficient introduction of test molecules into large populations of target cells, and the cytotoxicity of the techniques. A novel method of introducing genes and biomolecules into tens of thousands of mammalian cells has been developed through an array of aligned hollow carbon nanotubes, manufactured by template-based nanofabrication processes, to achieve rapid high-efficiency transfer with low cytotoxicity. The utilization of carbon nanotube arrays for gene transfection overcomes molecular weight limits of current technologies and can be adapted to deliver drugs or proteins in addition to nucleic acids.

Colorado Immersion Training in Community Engagement: Because You Can't Study What You Don't Know.

BACKGROUND: Community engagement (CE)has become a major element in medical research. In alliance with the goals of the Clinical and Translational Sciences Award program, Colorado Immersion Training in Community Engagement (CIT) is a community-campus partnership that aims to introduce an expanded pool of researchers to community-based participatory research (CBPR) and CE. OBJECTIVES: To describe CIT components and preliminary results. METHODS: CIT attempts to support a change in the research trajectory of academic health researchers, program developers, and graduate students toward CE. The program occurs on campus and in six community settings: Urban African American, urban Asian and refugee, urban Latino, urban American Indian/Alaska Native, rural northeast Colorado, and rural San Luis Valley. Components include a 4-week Directed Reading, a seminar on CBPR, 4-day community immersion, reflection, and 6-month support. Evaluation describes recruitment, implementation, and participants' understanding of CBPR and skills post-training. RESULTS: Fifty-eight people have participated. A comprehensive curriculum was developed to address (1) principals of CBPR, (2) health disparities, (3) listening to community, (4) self-reflection, and (5) engagement tools. Community immersions expose participants to a community's culture and opportunities to discuss health issues with a range of community members. Local "community guides" enhance participants' experience. Of the first two cohorts, 90% changed the way they plan to approach their research, 94% changed how they viewed community involvement in research, and 77% learned new skills to help engage communities in research. CONCLUSIONS: CIT applies to and positively impacts researchers from a variety of disciplines. CIT creates opportunities for long lasting partnerships between researchers and communities.

Assessing capacity for providing culturally competent services to LGBT older adults.

This qualitative, interview-based study assessed the cultural competence of health and social service providers to meet the needs of LGBT older adults in an urban neighborhood in Denver, Colorado, known to have a large LGBT community. Only 4 of the agencies were categorized as "high competency"; 12 were felt to be "seeking improvement" and 8 were considered "not aware." These results indicate significant gaps in cultural competency for the majority of service providers. Social workers are well-suited to lead efforts directed at improving service provision and care competencies for the older LGBT community.

Using PCR to Target Misconceptions about Gene Expression.

We present a PCR-based laboratory exercise that can be used with first- or second-year biology students to help overcome common misconceptions about gene expression. Biology students typically do not have a clear understanding of the difference between genes (DNA) and gene expression (mRNA/protein) and often believe that genes exist in an organism or cell only when they are expressed. This laboratory exercise allows students to carry out a PCR-based experiment designed to challenge their misunderstanding of the difference between genes and gene expression. Students first transform E. coli with an inducible GFP gene containing plasmid and observe induced and un-induced colonies. The following exercise creates cognitive dissonance when actual PCR results contradict their initial (incorrect) predictions of the presence of the GFP gene in transformed cells. Field testing of this laboratory exercise resulted in learning gains on both knowledge and application questions on concepts related to genes and gene expression.

Dual orientation of the outer membrane lipoprotein P6 of nontypeable haemophilus influenzae.

The majority of outer membrane (OM) lipoproteins in Gram-negative bacteria are tethered to the membrane via an attached lipid moiety and oriented facing in toward the periplasmic space; a few lipoproteins have been shown to be surface exposed. The outer membrane lipoprotein P6 from the Gram-negative pathogenic bacterium nontypeable Haemophilus influenzae (NTHi) is surface exposed and a leading vaccine candidate for prevention of NTHi infections. However, we recently found that P6 is not a transmembrane protein as previously thought (L. V. Michel, B. Kalmeta, M. McCreary, J. Snyder, P. Craig, M. E. Pichichero, Vaccine 29:1624-1627, 2011). Here we pursued studies to show that P6 has a dual orientation, existing infrequently as surface exposed and predominantly as internally oriented toward the periplasmic space. Flow cytometry using three monoclonal antibodies with specificity for P6 showed surface staining of whole NTHi cells. Confocal microscopy imaging confirmed that antibodies targeted surface-exposed P6 of intact NTHi cells and not internal P6 in membrane-compromised or dead cells. Western blots of two wild-type NTHi strains and a mutant NTHi strain that does not express P6 showed that P6 antibodies do not detect a promiscuous epitope on NTHi. Depletion of targets to nonlipidated P6 significantly decreased bactericidal activity of human serum. Protease digestion of surface-exposed P6 demonstrated that P6 is predominantly internally localized in a manner similar to its homologue Pal in Escherichia coli. We conclude that P6 of NTHi is likely inserted into the OM in two distinct orientations, with the predominant orientation facing in toward the periplasm.

Effects of alcohol cues and alcohol intoxication on drug use expectancies among men who have sex with men.

Although alcohol and drug use have been identified as HIV-risk factors for men who have sex with men (MSM), little is known about how they interact. An alcohol administration paradigm was used to examine alcohol's cue and pharmacological effects on perceived drug use benefits and consequences in 117 MSM. Planned contrasts indicated that those in the alcohol cue (i.e., placebo) condition reported lower perceived drug consequences compared to controls. No cue effects were found for drug benefits. There was no pharmacological effect of alcohol as compared to alcohol cue on either outcome. Findings suggest that alcohol cues may influence the perception of consequences related to drug use, which has implications for health interventions targeting substance use and HIV risk.

Quality and cost evaluation of a medical financial assistance program.

BACKGROUND: Kaiser Permanente Colorado has been responding to the financial challenges of its members by providing a medical financial assistance (MFA) program since 1992. However, there have been no evaluations of the effect of this program on members' use of health services or their health outcomes. METHODS: A prospective cohort study of 308 MFA program members who were enrolled between May 16, 2008, and May 16, 2009, examined changes in their use of health services, costs, and self-reported physical and mental health after enrollment in the MFA program. Use of services was analyzed with multiple regression, and costs of services with generalized linear models. RESULTS: MFA increased members' access to health services. There were no changes in physical or mental health status. For each health care visit before the MFA award, patients used the health care system 0.23 visits less. The MFA amount was not associated with an increase or decrease in use. There was no significant difference in total overall cost. Hospital costs were lower, but costs for clinic visits, pharmacy services, phone calls, and radiology services were significantly higher, resulting in service cost neutrality, possibly because financial barriers before MFA award led to accumulated demand for services. CONCLUSIONS: Use of services decreased after MFA was received. There was no significant change in total service cost. MFA improved members' ability to pay for medical services and increased their satisfaction with health services.

Patient-identified factors related to heart failure readmissions.

BACKGROUND: Although readmission after hospitalization for heart failure has received increasing attention, little is known about its root causes. Prior investigations have relied on administrative databases, chart review, and single-question surveys. METHODS AND RESULTS: We performed semistructured 30- to 60-minute interviews of patients (n=28) readmitted within 6 months of index heart failure admission. Established qualitative approaches were used to analyze and to interpret data. Interview findings were the primary focus of the study, but patient information and provider comments from chart data were also consulted. Patient median age was 61 years; 29% were nonwhite; 50% were married; 32% had preserved ejection fraction; and median time from discharge to readmission was 31 days. Reasons for readmission were multifactorial and not easily categorized into mutually exclusive reasons. Five themes emerged as reasons cited for hospital readmission: distressing symptoms, unavoidable progression of illness, influence of psychosocial factors, good but imperfect self-care adherence, and health system failures. CONCLUSIONS: Our study provides the first systematic qualitative assessment of patient perspectives concerning heart failure readmission. Contrary to prior literature and distinct from what we found documented in the medical record, patient experiences were highly heterogeneous, not easily categorized as preventable or not preventable, and not easily attributed to a single cause. These findings suggest that future interventions designed to reduce heart failure readmissions should be multifaceted, should be systemic in nature, and should integrate patient input.

Clinicians' implicit ethnic/racial bias and perceptions of care among Black and Latino patients.

PURPOSE: We investigated whether clinicians' explicit and implicit ethnic/racial bias is related to black and Latino patients' perceptions of their care in established clinical relationships. METHODS: We administered a telephone survey to 2,908 patients, stratified by ethnicity/race, and randomly selected from the patient panels of 134 clinicians who had previously completed tests of explicit and implicit ethnic/racial bias. Patients completed the Primary Care Assessment Survey, which addressed their clinicians' interpersonal treatment, communication, trust, and contextual knowledge. We created a composite measure of patient-centered care from the 4 subscales. RESULTS: Levels of explicit bias were low among clinicians and unrelated to patients' perceptions. Levels of implicit bias varied among clinicians, and those with greater implicit bias were rated lower in patient-centered care by their black patients as compared with a reference group of white patients (P = .04). Latino patients gave the clinicians lower ratings than did other groups (P <.0001), and this did not depend on the clinicians' implicit bias (P = .98). CONCLUSIONS: This is among the first studies to investigate clinicians' implicit bias and communication processes in ongoing clinical relationships. Our findings suggest that clinicians' implicit bias may jeopardize their clinical relationships with black patients, which could have negative effects on other care processes. As such, this finding supports the Institute of Medicine's suggestion that clinician bias may contribute to health disparities. Latinos' overall greater concerns about their clinicians appear to be based on aspects of care other than clinician bias.

Life goal appraisal and marijuana use among college students.

The current study was designed to examine the motivational context of marijuana use among college students using idiographic and nomothetic goal assessment approaches. One hundred and ninety-eight introductory psychology students completed a questionnaire that included measures of life goals and marijuana use behavior. Forty-three percent of students surveyed reported the use of marijuana in the past 90 days. Students rated a set of five personally salient, self-generated and five normative life goals on a series of dimensions using the personal projects methodology (Little, 1983). Goal meaning and goal efficacy ratings for each type of assessment were studied in relation to the likelihood of marijuana use and the frequency of use among current users. Logistic regression analyses showed that levels of meaning for self-generated life goals and normative academic life goals were independent predictors of whether students used marijuana in the past 90 days. Students who reported high levels of meaning were less likely to have used marijuana in the past 90 days. For students who used marijuana, higher meaning ratings related to involvement in groups/organizations and fitness were correlated with decreased frequency of use. Moreover, ratings of efficacy related to self-generated goals were associated with less frequent use among smokers. These results suggest that meaning related to life goal pursuit may be associated with students' decisions to use marijuana. Potential implications for interventions are discussed.