Faculty Bibliography

This study reports the first assessment of published comments in the family medicine literature using structured codes, which produced commentary annotations that will be the foundation of a knowledge base of appraisals of family medicine trials. Evidence appraisal occurs in a variety of formats and serves to shed light on the quality of research. However, scientific discourse generally and evidence appraisal in particular has not itself been analyzed for insights. A search strategy was devised to identify all journal comments indexed in PubMed linked to controlled intervention studies published in a recent 15-year period in major family medicine journals. A previously developed structured representation in the form of a list of appraisal concepts was used to formally annotate and categorize the journal comments through an iterative process. Trends in family medicine evidence appraisal were then analyzed. A total of 93 comments on studies from five journals over 15 years were included in the analysis. Two thirds of extracted appraisals were negative criticisms. All appraisals of measurement instruments were negative (100%). The participants baseline characteristics, the author discussions, and the design of the interventions were also criticized (respectively 91.7%, 84.6% and 83.3% negative). In contrast, appraisals of the scientific basis of the studies were positive (81.8%). The categories with the most appraisals were, most generally, those focused on the study design, and most specifically, those focused on the scientific basis. This study provides a new data-driven approach to review scientific discourse regarding the strengths and limitations of research within academic family medicine. This methodology can potentially generalize to other medical domains. Structured appraisal data generated here will enable future clinical, scientific, and policy decision-making and broader meta-research in family medicine.

Statement of Problem Or Question (One Sentence): How do we provide effective, dignified primary care for medically complex patients with homelessness in a safety-net health system? Objectives of Program/Intervention (No More Than Three Objectives): To effectively engage homeless patients with complex barriers to primary care To provide dignified, trauma-informed care focused on patient-oriented care goals while addressing addiction, mental health, and chronic disease To implement an interdisciplinary care team model in a safety-net health care system combining primary care, social work, care coordination, and nursing Description of Program/Intervention, Including Organizational Context (E.G. Inpatient Vs. Outpatient, Practice or Community Characteristics): Unstably housed people with complex chronic disease often receive fragmented care from various emergency departments and inpatient settings, accruing high rates of acute care utilization without improvements in health. Recently, intensive outpatient models have emerged to better manage high need patients. Here we describe our efforts to create a complex care clinic for medically, socially, and behaviorally complex patients with unstable housing at the largest safety-net health system in the United States. Launched in August 2018, the clinic aims to engage patients in a trusting healthcare environment and break the cycle of disease, addiction, and housing instability. Our team includes four buprenorphine-waivered internal medicine physicians, a social worker, care coordinator, and home care nurse provided by our system's Medicaid Health Home. Patients are referred from the ED, inpatient service, other clinics, street outreach organizations, shelters, and jails. They receive extensive care coordination; on-site addiction, medical, and social services; home nursing visits; and collaboration with shelters and community based organizations. Measures of Success (Discuss Qualitative And/Or Quantitative Metrics Which Will Be Used To Evaluate Program/Intervention): A quantitative analysis will be used to determine program impact on clinical outcomes and utilization, patient experience, and provider satisfaction. Both quantitative and qualitative measures will be used to evaluate clinic capacity, services provided, patient engagement, and progress towards patient-oriented care goals. Findings To Date (It Is Not Sufficient To State Findings Will Be Discussed): From August through December 2018, 156 referrals were given appointments and 83 patients completed at least one appointment. Of those, at least 44 patients (53%) returned for a second visit. On average patients completed 2.1 visits. We had a 16% cancellation rate and 38% no show rate. Patients are mostly male, middle-aged and street or shelter dwelling with common diagnosis of substance use disorder, lower extremity wounds, and hypertension. Our most engaged patients (> 3 visits, n=15) have seen an average reduction in ED visits by 68% and inpatient admissions by 58% within our system compared to pre-clinic intervention. Key Lessons For Dissemination (What Can Others Take Away For Implementation To Their Practice Or Community?): Relationships have been a core element of patient care, building an interdisciplinary team, and developing referral and collaborative resources internally and in the community. Our focus on a patient-directed care plan, warm hand-offs, continuity of care, and community outreach has also allowed this model to succeed

Randomized controlled trials can benefit from proactive assessment of how well their participant selection strategies during the design of eligibility criteria can influence the study generalizability. In this paper, we present a quantitative metric called generalizability index for study traits 2.0 (GIST 2.0) to assess the a priori generalizability (based on population representativeness) of a clinical trial by accounting for the dependencies among multiple eligibility criteria. The metric was evaluated on 16 sepsis trials identified from ClinicalTrials.gov, with their adverse event reports extracted from the trial results sections. The correlation between GIST scores and adverse events was analyzed. We found that the GIST 2.0 score was significantly correlated with total adverse events and serious adverse events (weighted correlation coefficients of 0.825 and 0.709, respectively, with P < 0.01). This study exemplifies the promising use of Big Data in electronic health records and ClinicalTrials.gov for optimizing eligibility criteria design for clinical studies.

The design of randomized controlled clinical studies can greatly benefit from iterative assessments of population representativeness of eligibility criteria. We propose a multi-trait metric - GIST 2.0 that can compute the a priori generalizability based on the population representativeness of a clinical study by explicitly modeling the dependencies among all eligibility criteria. We evaluate this metric on twenty clinical studies of two diseases and analyze how a study's eligibility criteria affect its generalizability (collectively and individually). We statistically analyze the effects of trial setting, trait selection and trait summarizing technique on GIST 2.0. Finally we provide theoretical as well as empirical validations for the expected properties of GIST 2.0.

BACKGROUND: Integration of retroviral DNA into the host cell genome is an obligatory step in the virus life cycle. In previous reports we identified a sequence (amino acids 201-236) in the linker region between the catalytic core and C-terminal domains of the avian sarcoma virus (ASV) integrase protein that functions as a transferable nuclear localization signal (NLS) in mammalian cells. The sequence is distinct from all known NLSs but, like many, contains basic residues that are essential for activity. RESULTS: Our present studies with digitonin-permeabilized HeLa cells show that nuclear import mediated by the NLS of ASV integrase is an active, saturable, and ATP-dependent process. As expected for transport through nuclear pore complexes, import is blocked by treatment of cells with wheat germ agglutinin. We also show that import of ASV integrase requires soluble cellular factors but does not depend on binding the classical adapter Importin-alpha. Results from competition studies indicate that ASV integrase relies on one or more of the soluble components that mediate transport of the linker histone H1. CONCLUSION: These results are consistent with a role for ASV integrase and cytoplasmic cellular factors in the nuclear import of its viral DNA substrate, and lay the foundation for identification of host cell components that mediate this reaction.