Testing the validity and reliability of the Person-Centered Contraceptive Counseling (PCCC) Performance Measure in a Real-World Contraceptive Access Program.

OBJECTIVES: To validate the Person-Centered Contraceptive Counseling (PCCC) patient-reported outcome performance measure and assess for differences by sociodemographic attributes using survey data from a multistate contraceptive access program. STUDY DESIGN: This analysis explored internal reliability and construct validity of the PCCC using survey data from 1413 patients who visited 15 health centers in Washington state and Massachusetts that had partnered with Upstream USA. RESULTS: Multiple psychometric indicators provided evidence of reliability and validity. Significant associations between the highest PCCC rating and conceptually-related survey questions (i.e., experience with bias/coercion and shared decision-making) provided further evidence of construct validity. CONCLUSIONS: Our findings demonstrate that the PCCC is valid and reliable. The results also highlight differences in experience of care by patient-reported race and ethnicity, income level, and language.

Novel Ex Vivo Zymography Approach for Assessment of Protease Activity in Tissues with Activatable Antibodies.

Proteases are involved in the control of numerous physiological processes, and their dysregulation has been identified in a wide range of pathologies, including cancer. Protease activity is normally tightly regulated post-translationally and therefore cannot be accurately estimated based on mRNA or protein expression alone. While several types of zymography approaches to estimate protease activity exist, there remains a need for a robust and reliable technique to measure protease activity in biological tissues. We present a novel quantitative ex vivo zymography (QZ) technology based on Probody® therapeutics (Pb-Tx), a novel class of protease-activated cancer therapeutics that contain a substrate linker cleavable by tumor-associated proteases. This approach enables the measurement and comparison of protease activity in biological tissues via the detection of Pb-Tx activation. By exploiting substrate specificity and selectivity, cataloguing and differentiating protease activities is possible, with further refinement achieved using protease-specific inhibitors. Using the QZ assay and human tumor xenografts, patient tumor tissues, and patient plasma, we characterized protease activity in preclinical and clinical samples. The QZ assay offers the potential to increase our understanding of protease activity in tissues and inform diagnostic and therapeutic development for diseases, such as cancer, that are characterized by dysregulated proteolysis.

Utility of a virtual counselor (VICKY) to collect family health histories among vulnerable patient populations: A randomized controlled trial.

OBJECTIVES: This study is a randomized controlled trial comparing the efficacy of a virtual counselor (VICKY) to the My Family Health Portrait (MFHP) tool for collecting family health history (FHx). METHODS: A total of 279 participants were recruited from a large safety-net hospital and block randomized by health literacy to use one of the digital FHx tools, followed by a genetic counselor interview. A final sample of 273 participants were included for analyses of primary study aims pertaining to tool concordance, which assessed agreement between tool and genetic counselor. RESULTS: Tool completion differed significantly between tools (VICKY = 97%, MFHP = 51%; p < .0001). Concordance between tool and genetic counselor was significantly greater for participants randomized to VICKY compared to MFHP for ascertaining first- and second-degree relatives (ps<.0001), and most health conditions examined. There was significant interaction by health literacy, with greater differences in concordance observed between tools among those with limited literacy. CONCLUSIONS: A virtual counselor overcomes many of the literacy-related barriers to using traditional digital tools and highlights an approach that may be important to consider when collecting health histories from vulnerable populations. PRACTICE IMPLICATIONS: The usability of digital health history tools will have important implications for the quality of the data collected and its downstream clinical utility.

Influence of Family and Community Socioeconomic Status on the Risk of Adolescent Drug Use.

Background: Adolescent drug use increases the risk of mental, physical and social problems later in life and so it is important to understand its complex etiology that likely includes socioeconomic status (SES). We undertook the present analysis using data from a population-based retrospective cohort study to examine the influence of family and community SES in relation to adolescent drug use. We hypothesized that lower levels of community and parental SES would increase the risk of use and that there would be stronger associations for the more proximate family-level factors. Methods: We used self-administered questionnaires (N=1,402) to obtain information on use of marijuana, inhalants, heroin, cocaine/crack, psychedelics/hallucinogens, Ritalin without a prescription, and club drugs during adolescence. Family SES was gathered from birth certificate data on maternal educational level and paternal occupation. Community SES characteristics at birth, age 10 and age 18 were obtained from the US Census Bureau. Results: An increased risk of adolescent drug use was associated with lower maternal education, non-white collar occupations among fathers, and lower community median income, and poverty and unemployment levels at age 18. The strongest associations were seen for the use of multiple drugs (Risk Ratio (RR): 1.7, 95% CI: 1.4-2.2), inhalants (RR: 2.5, 95% CI: 1.5-2.2), crack/cocaine (RR: 2.8, 95% CI: 1.7-4.5), psychedelics/hallucinogens (RR: 1.8, 95% CI: 1.4-2.4), and club/designer drugs (RR: 1.8, 95% CI: 1.2-2.7) among adolescents whose mothers had only a high school education. Conclusions: These results suggest that use of certain drugs during adolescence is associated with both family and community SES measures. However, maternal education appears to have the greatest influence on use, suggesting that a multi-level approach that engages mothers is needed to prevent adolescent drug use.

Designing and Evaluating a Digital Family Health History Tool for Spanish Speakers.

Digital family health history tools have been developed but few have been tested with non-English speakers and evaluated for acceptability and usability. This study describes the cultural and linguistic adaptation and evaluation of a family health history tool (VICKY: VIrtual Counselor for Knowing Your Family History) for Spanish speakers. In-depth interviews were conducted with 56 Spanish-speaking participants; a subset of 30 also participated in a qualitative component to evaluate the acceptability and usability of Spanish VICKY. Overall, agreement in family history assessment was moderate between VICKY and a genetic counselor (weighted kappa range: 0.4695 for stroke-0.6615 for heart disease), although this varied across disease subtypes. Participants felt comfortable using VICKY and noted that VICKY was very likeable and possessed human-like characteristics. They reported that VICKY was very easy to navigate, felt that the instructions were very clear, and thought that the time it took to use the tool was just right. Spanish VICKY may be useful as a tool to collect family health history and was viewed as acceptable and usable. The study results shed light on some cultural differences that may influence interactions with family history tools and inform future research aimed at designing and testing culturally and linguistically diverse digital systems.

Health Literacy and Income Mediate Racial/Ethnic Asthma Disparities.

BACKGROUND: Health literacy and socioeconomic status (SES) are associated with both race/ethnicity and asthma outcomes. The extent to which health literacy and SES mediate racial/ethnic asthma disparities is less clear. OBJECTIVE: To determine if health literacy and SES mediate racial/ethnic asthma disparities using advanced mediation analyses. METHODS: A secondary analysis was performed using a Chicago-based longitudinal cohort study conducted from 2004 to 2007 involving 342 adults age 18 to 41 years with persistent asthma. Phone interviews were conducted every 3 months assessing asthma quality of life (AQOL; scored 1-7, with 7 being the highest) and asthma-related health care use measures. Structural equation models assessed mediation of race/ethnicity effects on AQOL and health care use through health literacy and SES. Covariates in the best-fit model included sex, year and season of interview, and cigarette smoking. KEY RESULTS: The study sample was 77.8% female, 57.3% African American/non-Hispanic, and 28.7% Hispanic. Race/ethnicity was significantly associated with AQOL and asthma-related emergency department (ED) visits, but only indirectly, through the effects of health literacy and income. Compared with White/non-Hispanics, African American/non-Hispanics and Hispanics had significantly higher odds of low health literacy and lower income. Low health literacy was associated with significantly lower AQOL scores (ß = -0.24, 95% confidence interval (CI) [-0.38, -0.10]) and higher odds of an ED visit (adjusted odds ratio = 1.24, 95% CI [1.07, 1.43]). Increasing income was associated with significantly higher AQOL scores (ß = 0.18, 95% CI [0.08, 0.28]) and lower odds of an ED visit (adjusted odds ratio = 0.88, 95% CI [0.80, 0.97]). CONCLUSIONS: The relationships between race/ethnicity and several asthma outcomes were mediated by health literacy and income. Interventions to improve racial/ethnic asthma disparities should target health literacy and income barriers. [HLRP: Health Literacy Research and Practice. 2019;3(1):e9-e18.]. PLAIN LANGUAGE SUMMARY: Using advanced statistical methods, this study suggests racial/ethnic differences in several asthma outcomes are largely due to effects of health literacy and income. Interventions to improve racial/ethnic asthma disparities should target health literacy and income barriers.

Assessment of Preclinical Liver and Skeletal Muscle Biomarkers Following Clofibrate Administration in Wistar Rats.

Clofibrate is a known rodent hepatotoxicant classically associated with hepatocellular hypertrophy and increased serum activities of cellular alanine aminotransferase/aspartate aminotransferase (ALT/AST) in the absence of microscopic hepatocellular degeneration. At toxic dose, clofibrate induces liver and skeletal muscle injury. The objective of this study was to assess novel liver and skeletal muscle biomarkers following clofibrate administration in Wistar rats at different dose levels for 7 days. In addition to classical biomarkers, liver injury was assessed by cytokeratin 18 (CK18) cleaved form, high-mobility group box 1, arginase 1 (ARG1), microRNA 122 (miR-122), and glutamate dehydrogenase. Skeletal muscle injury was evaluated with fatty acid binding protein 3 (Fabp3) and myosin light chain 3 (Myl3). Clofibrate-induced hepatocellular hypertrophy and skeletal muscle degeneration (type I rich muscles) were noted microscopically. CK, Fabp3, and Myl3 elevations correlated to myofiber degeneration. Fabp3 and Myl3 outperformed CK for detection of myofiber degeneration of minimal severity. miR-122 and ARG1 results were significantly correlated and indicated the absence of liver toxicity at low doses of clofibrate, despite increased ALT/AST activities. Moreover, combining classical and novel biomarkers (Fabp3, Myl3, ARG1, and miR-122) can be considered a valuable strategy for differentiating increased transaminases due to liver toxicity from skeletal muscle toxicity.

Patient Activation Mediates Health Literacy Associated with Hospital Utilization among Whites.

BACKGROUND: Reducing the 30-day hospital readmission rate is a national priority and patient activation has emerged as a modifiable target to reduce hospital readmissions. OBJECTIVE: Prior studies demonstrate that low patient activation and low health literacy are each associated with higher rates of hospital utilization. The aim of this study was to use path analysis methods to assess if patient activation mediates the relationship between health literacy and hospital utilization in the 30 days after discharge. DESIGN AND PARTICIPANTS: We performed a secondary analysis of data from a randomized controlled trial of patients receiving care at an urban safety net hospital. Path analyses were used to assess patient activation as a mediator of the relationship of education and health literacy with 30-day hospital utilization. The final model was stratified by race and ethnicity. MEASURE: 30 day Hospital Utilization. RESULTS: In the overall study sample, a one standard deviation (SD) higher patient activation measure (PAM) score was associated with 18% reduced odds of hospital utilization (odds ratio (OR) 0.82, 95% confidence interval (CI): 0.73, 0.91, p=<0.001). PAM mediated the relationship between education level and health literacy and hospital utilization. When stratified by race, the mediating effect of PAM was evident among Whites, but not among non-Whites. Specifically, a one SD higher PAM score was significantly associated with a 33% reduced odds of utilization among Whites (OR 0.67, 95% CI: 0.57, 0.79, p<0.001). With the inclusion of PAM in the model, there was no direct relationship between either health literacy or education and 30-day hospital utilization. CONCLUSION: Patient activation is only associated with hospital utilization among Whites. Further research is needed to assess if this selective protection is seen in other cohorts. Potential interventions to reduce hospital readmissions may need to consider other modifiable factors in racially and ethnically diverse populations.

Health Literacy and Education as Mediators of Racial Disparities in Patient Activation Within an Elderly Patient Cohort.

The Patient Activation Measure (PAM) assesses facets of patient engagement to identify proactive health behaviors and is an important predictor of health outcomes. Health literacy and education are also important for patient participation and successful navigation of the health care system. Because health literacy, education, and patient activation are associated with racial disparities, we sought to investigate whether health literacy and education would mediate racial differences in patient activation. Participants were 265 older adults who participated in a computer-based exercise interventional study. Health literacy was assessed using the Test of Functional Health Literacy in Adults (TOFHLA). Of 210 eligible participants, 72% self-identified as Black and 28% as White. In adjusted analyses, education and health literacy each significantly reduced racial differences in patient activation. These findings are especially important when considering emerging data on the significance of patient activation and new strategies to increase patient engagement.

Disparities in Age-Associated Cognitive Decline Between African-American and Caucasian Populations: The Roles of Health Literacy and Education.

OBJECTIVES: To examine health literacy as a mediator of racial disparities in cognitive decline as measured by executive function in elderly adults. DESIGN: Prospective cohort study. SETTING: Secondary analysis of ElderWalk trial in Boston, Massachusetts. PARTICIPANTS: English-speaking African-American and Caucasian individuals in a walking intervention for community-dwelling adults aged 65 and older without dementia at baseline who completed baseline and 12-month evaluations (N = 198). MEASUREMENTS: Health literacy was measured using the Short Test of Functional Health Literacy in Adults. Fluid and crystallized cognitive functions were measured at baseline and 12 months using the Trail-Making Test Part B minus Part B (TMT B-A) and the Controlled Oral Word Association Test (COWAT). Associations between health literacy and 12-month cognitive decline were modeled using multivariate linear regression. RESULTS: Participants with higher health literacy and education experienced less cognitive decline than those with limited health literacy according to the TMT B-A (P = .01). After adjusting for covariates, Caucasian participants (n = 63) experienced less decline than African-American participants (n = 135) on TMT B-A (P = .001) and COWAT (P = .001). Adjusting for health literacy led to a 25.3% decrease in the point estimate for racial difference in TMT B-A and a 19.5% decrease in COWAT. Although independently related to cognitive decline, educational attainment did not mediate racial differences. CONCLUSION: Health literacy is a partial mediator of racial disparities in cognitive decline. These results indicate the need to develop interventions to mitigate cognitive decline that individuals with low heath literacy can use and to modify the healthcare environment to better accommodate this population.

Racial disparities in patient activation: Evaluating the mediating role of health literacy with path analyses.

OBJECTIVE: The aim of this study was to use path analysis methods to determine if health literacy mediates the relationship between race and patient activation. METHODS: We performed a secondary analysis of data from a randomized controlled trial in elderly, urban, minority patients using path analysis. Path analysis was used to evaluate the mediation of race on patient activation through different variables. Several models were tested for best fit for their effects on patient activation. RESULTS: Across all models, significant mediation paths were identified from race to lower patient activation through health literacy. This relationship remained significant throughout alternative model testing for covariate combinations. The best-fit model included an indirect effect of sex on patient activation through health literacy indicating that the mediation effect of health literacy on patient activation was most profound for African American males. Health literacy had a bigger influence on patient activation for participants with a greater comorbidity than for those with fewer conditions. No significant direct effect was shown between race and patient activation in any of the models. CONCLUSION: Racial disparities in patient activation were fully mediated by health literacy skills. PRACTICE IMPLICATIONS: Future interventions to improve racial disparities in patient activation need to be targeted at improving health literacy.

Association of visit-to-visit variability of hemoglobin A1c and medication adherence.

BACKGROUND: Medication nonadherence is widespread, but there are few efficient means of detecting medication nonadherence at the point of care. Visit-to-visit variability in clinical biomarkers has shown inconsistent efficiency to predict medication adherence. OBJECTIVE: To examine the performance of visit-to-visit variability (VVV) of hemoglobin A1c to predict nonadherence to antidiabetic medications. METHODS: In this cross-sectional study using a clinical and administrative database, adult members of a managed care plan at a safety-net medical center from 2008 to 2012 were included if they had ≥ 3 noninsulin antidiabetic prescription fills within the same class and ≥ 3 A1c measurements between the first and last prescription fills. The independent variable was VVV of A1c (within-subject standard deviation of A1c), and the dependent variable was medication adherence (defined by medication possession ratio) determined from pharmacy claims. Unadjusted and adjusted multivariate logistic regression models were created to examine the relationship between VVV of A1c and medication nonadherence. Receiver-operating characteristic (ROC) curves assessed the performance of the adjusted model at discriminating adherence from nonadherence. RESULTS: Among 632 eligible subjects, mean A1c was 7.7% ± 1.3%, and 83% of the sample was nonadherent to antidiabetic medications. Increasing quintiles of VVV of A1c and medication nonadherence were both associated with increased within-subject mean A1c and younger subject age. The logistic regression model (adjusted for age, sex, race/ethnicity, within-subject mean A1c, number of A1c measurements, number of days between the first and last antidiabetic medication prescription fills, and rate of primary care visits during the study period) showed a nonsignificant association of VVV of A1c and medication nonadherence (OR = 1.19, 95% CI = 0.42-3.38 for the highest quintile of VVV). Adding VVV of A1c to a model including age, sex, and race only modestly improved the C-statistic of the ROC curve from 0.6786 to 0.7064. CONCLUSIONS: VVV of A1c is not a robust predictor of antidiabetic medication nonadherence. Further innovation is needed to develop novel methods of detecting nonadherence.

Screening for unhealthy alcohol and other drug use by health educators: do primary care clinicians document screening results?

OBJECTIVES: Health educators are increasingly being used to deliver preventive care including screening and brief intervention (SBI) for unhealthy substance use (SU) (alcohol or drug). There are few data, however, about the "handoff" of information from health educator to primary care clinician (PCC). Among patients identified with unhealthy SU and counseled by health educators, the objective of this study was to examine (1) the proportion of PCC notes with documentation of SBI and (2) the spectrum of SU not documented by PCCs. METHODS: Before the PCC-patient encounter, health educators screened for SU, assessed severity (Alcohol, Smoking, and Substance Involvement Screening Test), and counseled patients. They also conveyed this information to the PCC before the PCC-patient encounter. Researchers reviewed the electronic medical record for PCC documentation of SBI performed by the health educator and/or the PCC. RESULTS: Among patients with the health educator-identified SU, only 69% (342/495) of PCC notes contained documentation of screening by the health educator and/or the PCC. Documentation was found in all encounters with patients with likely dependent SU, but only 62% and 59% of encounters with patients with risky alcohol and drug use, respectively. Documentation of cocaine or heroin use was higher than that of alcohol or marijuana use but still not universal. Although all SU-identified patients had received a brief intervention (from a health educator and possibly a PCC), only 25% of PCC notes contained documentation of a brief intervention. CONCLUSIONS: Among patients screened and counseled by health educators for unhealthy SU, SBI was often not documented by PCCs. These results suggest that strategies are needed to integrate SBI by primary care team members to advance the quality of care for patients with unhealthy SU.

Primary care quality and addiction severity: a prospective cohort study.

BACKGROUND: Alcohol and drug use disorders are chronic diseases that require ongoing management of physical, psychiatric, and social consequences. While specific addiction-focused interventions in primary care are efficacious, the influence of overall primary care quality (PCQ) on addiction outcomes has not been studied. The aim of this study was to prospectively examine if higher PCQ is associated with lower addiction severity among patients with substance use disorders. STUDY POPULATION: Subjects with alcohol, cocaine, and/or heroin use disorders who initiated primary care after being discharged from an urban residential detoxification program. MEASUREMENTS: We used the Primary Care Assessment Survey (PCAS), a well-validated, patient-completed survey that measures defining attributes of primary care named by the Institute of Medicine. Nine summary scales cover two broad areas of PCQ: the patient-physician relationship (communication, interpersonal treatment, thoroughness of the physical exam, whole-person knowledge, preventive counseling, and trust) and structural/organizational features of care (organizational access, financial access, and visit-based continuity). Each of the three addiction outcomes (alcohol addiction severity (ASI-alc), drug addiction severity (ASI-drug), and any drug or heavy alcohol use) were derived from the Addiction Severity Index and assessed 6-18 months after PCAS administration. Separate longitudinal regression models included a single PCAS scale as the main predictor variable as well as variables known to be associated with addiction outcomes. MAIN RESULTS: Eight of the nine PCAS scales were associated with lower alcohol addiction severity at follow-up (p

Need and non-need factors associated with addiction treatment utilization in a cohort of homeless and housed urban poor.

BACKGROUND: Research on addiction treatment utilization in indigent samples mainly has been retrospective, without measures of addictive consequences, social network influences, and motivation. Prospective assessment of factors influencing utilization could inform policy and clinical care. OBJECTIVE: We sought to identify factors associated with utilization of addiction treatment and mutual help groups among substance-dependent persons with high rates of homelessness. RESEARCH AND METHODS: This was a prospective cohort of patients detoxified from alcohol or drugs at baseline who were followed for 2 years in a randomized clinical trial of linkage to primary care (n = 274). Outcomes included utilization of Inpatient/Residential, Outpatient, Any Treatment, and Mutual Help Groups. Predictor variables in longitudinal regression analyses came from the literature and clinical experience, organized according to theoretical categories of Need, and non-Need (eg, Predisposing and Enabling). RESULTS: Many subjects used Inpatient/Residential (72%), Outpatient (62%), Any Treatment (88%) or Mutual Help Groups (93%) at least once. In multivariable analyses, addictive consequences (odds ratio [OR] 1.38, 95% confidence interval [CI] 1.12-1.71), motivation (OR 1.32, 95% CI 1.09-1.60), and female gender (OR 1.80, 95% CI 1.13-2.86) were associated with most treatment types (ORs are for Any Treatment). Homelessness was associated with Residential/Inpatient (for Chronically Homeless vs. Housed, OR 1.75, 95% CI 1.04-2.94). Living with one's children (OR 0.51, 95% CI 0.31-0.84) and substance-abusing social environment (OR 0.65, 95% CI 0.43-0.98) were negatively associated with Any Treatment. CONCLUSIONS: In this cohort of substance-dependent persons, addictive consequences, social network variables, and motivation were associated with treatment utilization. Non-need factors, including living with one's children and gender, also were significant.

Magnitude of alcohol-related mortality and morbidity among U.S. college students ages 18-24: changes from 1998 to 2001.

Integrating data from the National Highway Traffic Safety Administration, the Centers for Disease Control and Prevention, national coroner studies, census and college enrollment data for 18-24-year-olds, the National Household Survey on Drug Abuse, and the Harvard College Alcohol Survey, we calculated the alcohol-related unintentional injury deaths and other health problems among college students ages 18-24 in 1998 and 2001. Among college students ages 18-24 from 1998 to 2001, alcohol-related unintentional injury deaths increased from nearly 1600 to more than 1700, an increase of 6% per college population. The proportion of 18-24-year-old college students who reported driving under the influence of alcohol increased from 26.5% to 31.4%, an increase from 2.3 million students to 2.8 million. During both years more than 500,000 students were unintentionally injured because of drinking and more than 600,000 were hit/assaulted by another drinking student. Greater enforcement of the legal drinking age of 21 and zero tolerance laws, increases in alcohol taxes, and wider implementation of screening and counseling programs and comprehensive community interventions can reduce college drinking and associated harm to students and others.

Linkage with primary medical care in a prospective cohort of adults with addictions in inpatient detoxification: room for improvement.

OBJECTIVE: To identify patient characteristics and health care experiences associated with primary care linkage after alcohol or drug detoxification. DATA SOURCES/STUDY SETTING: Primary data collected over two years. Subjects were adults without primary medical care, in an urban residential detoxification program. STUDY DESIGN: A prospective cohort study in the context of a randomized trial of a linkage intervention, and an expansion of Medicaid benefits. DATA COLLECTION/EXTRACTION METHODS: Data were collected by interview assessment of predisposing, enabling, and illness variables. Linkage was defined as self-report of at least one visit with a primary care clinician during follow-up. PRINCIPAL FINDINGS: Of 400 subjects, 63 percent linked with primary medical care. In a multivariable model adjusting for randomization assignment, predisposing, enabling, and illness variables, women, those with no recent incarceration, those with support for abstinence by family or friends, and those who had visited a medical clinic or physician recently were significantly more likely to link with primary care. Those with health insurance during follow-up were also more likely to link. Recent mental health or addictions treatment utilization and health status were not associated with linkage. CONCLUSIONS: A substantial proportion of adults with addictions do not link with primary medical care. These data suggest that efforts could be focused on those least likely to link, that contacts with mental health and addictions treatment providers are underutilized opportunities for these efforts, and that health policy changes such as expanding health insurance benefits may improve entry of substance-dependent patients into primary medical care.