Suzanne E. Mitchell

HOST-PARASITE AND GENOTYPE-BY-ENVIRONMENT INTERACTIONS: TEMPERATURE MODIFIES POTENTIAL FOR SELECTION BY A STERILIZING PATHOGEN

Abstract Parasite‐mediated selection is potentially of great importance in modulating genetic diversity. Genetic variation for resistance, the fuel for natural selection, appears to be common in host‐parasite interactions, but responses to selection are rarely observed. In the present study, we tested whether environmental variation could mediate infection and determine evolutionary outcomes. Temperature was shown to dramatically alter the potential for parasite‐mediated selection in two independent laboratory infection experiments at four temperatures. The bacterial parasite, Pasteuria ramosa, was extremely virulent at 20d̀C and 25d̀C, sterilizing its host, Daphnia magna, so that females often never produced a single brood. However, at 10d̀C and 15d̀C, the host‐parasite interaction was much more benign, as nearly all females produced broods before becoming sterile. This association between virulence and temperature alone could stabilize coexistence and lead to the maintenance of diversity, because it would weaken parasite‐mediated selection during parts of the season. Additionally, highly significant genotype‐by‐environment interactions were found, with changes in clone rank order for infection rates at different temperatures. Our results clearly show that the outcome of parasite‐mediated selection in this system is strongly context dependent.

Poor maternal environment enhances offspring disease resistance in an invertebrate

Natural populations vary tremendously in their susceptibility to infectious disease agents. The factors (environmental or genetic) that underlie this variation determine the impact of disease on host population dynamics and evolution, and affect our capacity to contain disease outbreaks and to enhance resistance in agricultural animals and disease vectors. Here, we show that changes in the environmental conditions under which female Daphnia magna are kept can more than halve the susceptibility of their offspring to bacterial infection. Counter-intuitively, and unlike the effects typically observed in vertebrates for transfer of immunity, mothers producing offspring under poor conditions produced more resistant offspring than did mothers producing offspring in favourable conditions. This effect occurred when mothers who were well provisioned during their own development then found themselves reproducing in poor conditions. These effects likely reflect adaptive optimal resource allocation where better quality offspring are produced in poor environments to enhance survival. Maternal exposure to parasites also reduced offspring susceptibility, depending on host genotype and offspring food levels. These maternal responses to environmental conditions mean that studies focused on a single generation, and those in which environmental variation is experimentally minimized, may fail to describe the crucial parameters that influence the spread of disease. The large maternal effects we report here will, if they are widespread in nature, affect disease dynamics, the level of genetic polymorphism in populations, and likely weaken the evolutionary response to parasite-mediated selection.

Health Literacy and 30-Day Postdischarge Hospital Utilization

Low health literacy is associated with higher mortality, higher rates of hospitalization, and poor self-management skills for chronic disease. Early, unplanned hospital reutilization after discharge is a common and costly occurrence in U.S. hospitals. Still, few studies have examined the relation between health literacy and 30-day hospital reutilization rates. The authors examined the association between health literacy and 30-day reutilization of hospital services (readmission or return to the emergency department) in an urban safety net hospital, and conducted a secondary analysis of data from the control arm subjects of the Project RED and the RED-LIT trials. Health literacy was measured using the REALM tool. The primary outcome was rate of 30-day reutilization. The authors used multivariate Poisson regression analysis to control for potential confounding. Of the 703 subjects, 20% had low health literacy, 29% had marginal health literacy, and 51% had adequate health literacy. Sixty-two percent of subjects had a 12th-grade education or less. Subjects with low health literacy were more likely to be insured by Medicaid (p < .001); Black non-Hispanic (p < .001); unemployed, disabled, or retired (p < .001); low income (p < .001); and less educated (high school education or less, p < .001). The fully adjusted incidence rate ratio for low health literacy compared with adequate health literacy was 1.46 (CI [1.04, 2.05]). Low health literacy is a significant, independent, and modifiable risk factor for 30-day hospital reutilization after discharge. Interventions designed to reduce early, unplanned, hospital utilization after discharge should include activities to mitigate the effect of patients’ low health literacy.

A Pilot Study of Motivational Interviewing Training in a Virtual World

Background Motivational interviewing (MI) is an evidence-based, patient-centered counseling strategy proven to support patients seeking health behavior change. Yet the time and travel commitment for MI training is often a barrier to the adoption of MI by health care professionals. Virtual worlds such as Second Life (SL) are rapidly becoming part of the educational technology landscape and offer not only the potential to improve access to MI training but also to deepen the MI training experience through the use of immersive online environments. Despite SL’s potential for medical education applications, little work is published studying its use for this purpose and still less is known of educational outcomes for physician training in MI using a virtual-world platform. Objective Our aims were to (1) explore the feasibility, acceptability, and effectiveness of a virtual-world platform for delivering MI training designed for physicians and (2) pilot test instructional designs using SL for MI training. Methods We designed and pilot tested an MI training program in the SL virtual world. We trained and enrolled 13 primary care physicians in a two-session, interactive program in SL on the use of MI for counseling patients about colorectal cancer screening. We measured self-reported changes in confidence and clinical practice patterns for counseling on colorectal cancer screening, and acceptability of the virtual-world learning environment and the MI instructional design. Effectiveness of the MI training was assessed by coding and scoring tape-recorded interviews with a blinded mock patient conducted pre- and post-training. Results A total of 13 physicians completed the training. Acceptability ratings for the MI training ranged from 4.1 to 4.7 on a 5-point scale. The SL learning environment was also highly rated, with 77% (n = 10) of the doctors reporting SL to be an effective educational medium. Learners’ confidence and clinical practice patterns for colorectal cancer screening improved after training. Pre- to post-training mean confidence scores for the ability to elicit and address barriers to colorectal cancer screening (4.5 to 6.2, P = .004) and knowledge of decision-making psychology (4.5 to 5.7, P = .02) and behavior change psychology (4.9 to 6.2, P = .02) increased significantly. Global MI skills scores increased significantly and component scores for the MI skills also increased, with statistically significant improvements in 4 of the 5 component skills: empathy (3.12 to 3.85, P = .001), autonomy (3.07 to 3.85, P < .001), collaboration (2.88 to 3.46, P = .02), and evocative response (2.80 to 3.61, P = .008). Conclusions The results of this pilot study suggest that virtual worlds offer the potential for a new medical education pedagogy that will enhance learning outcomes for patient-centered communication skills training.

Acute care hospital utilization among medical inpatients discharged with a substance use disorder diagnosis.

Objective:Hospital discharge may be an opportunity to intervene among patients with substance use disorders to reduce subsequent hospital utilization. This study determined whether having a substance use disorder diagnosis was associated with subsequent acute care hospital utilization. Methods:We conducted an observational cohort study among 738 patients on a general medical service at an urban, academic, safety-net hospital. The main outcomes were rate and risk of acute care hospital utilization (emergency department visit or hospitalization) within 30 days of discharge. The main independent variable was presence of a substance use disorder primary or secondary discharge diagnosis code at the index hospitalization. Results:At discharge, 17% of subjects had a substance use disorder diagnosis. These patients had higher rates of recurrent acute care hospital utilization than patients without substance use disorder diagnoses (0.63 vs 0.32 events per subject at 30 days, P < 0.01) and increased risk of any recurrent acute care hospital utilization (33% vs 22% at 30 days, P < 0.05). In adjusted Poisson regression models, the incident rate ratio at 30 days was 1.49 (95% confidence interval, 1.12–1.98) for patients with substance use disorder diagnoses compared with those without. In subgroup analyses, higher utilization was attributable to those with drug diagnoses or a combination of drug and alcohol diagnoses, but not to those with exclusively alcohol diagnoses. Conclusions:Medical patients with substance use disorder diagnoses, specifically those with drug use-related diagnoses, have higher rates of recurrent acute care hospital utilization than those without substance use disorder diagnoses.

Post-discharge hospital utilization among adult medical inpatients with depressive symptoms†

BACKGROUND Little evidence exists to determine whether depression predicts hospital utilization following discharge among adult inpatients on a general medical service. OBJECTIVE We aimed to determine whether a positive depression screen during hospitalization is significantly associated with an increased rate of returning for hospital services. DESIGN A secondary analysis was performed using data from 738 English-speaking, hospitalized adults from the Project RED randomized controlled trial (clinicaltrials.gov Identifier: NCT00252057) conducted at an urban academic safety-net hospital. MEASUREMENTS We used the nine-item Patient Health Questionnaire (PHQ-9) depression screening tool to identify patients with depressive symptoms. The primary endpoint was hospital utilization, defined as the number of emergency department (ED) visits plus readmissions within 30 days of discharge. Poisson regression was used to control for confounding variables. RESULTS Of the 738 subjects included in the analysis, 238 (32%) screened positive for depressive symptoms. The unadjusted hospital utilization within 30 days of discharge was 56 utilizations per 100 depressed patients compared with 30 utilizations per 100 non-depressed patients, incident rate ratio (IRR) (confidence interval [CI]), 1.90 (1.51-2.40). After controlling for potential confounders, a higher rate of post-discharge hospital utilization was observed in patients with depressive symptoms compared to patients without depressive symptoms (IRR [CI], 1.73 [1.27-2.36]). CONCLUSIONS A positive screen for depressive symptoms during an inpatient hospital stay is associated with an increased rate of readmission within 30 days of discharge in an urban, academic, safety-net hospital population.

Response to a relational agent by hospital patients with depressive symptoms

Depression affects approximately 15% of the US population, and is recognized as an important risk factor for poor outcomes among patients with various illnesses. Automated health education and behavior change programs have the potential to help address many of the shortcomings in health care. However, the role of these systems in the care of patients with depression has been insufficiently examined. In the current study, we sought to evaluate how hospitalized medical patients would respond to a computer animated conversational agent that has been developed to provide information in an empathic fashion about a patients hospital discharge plan. In particular, we sought to examine how patients who have a high level of depressive symptoms respond to this system. Therapeutic alliance-the trust and belief that a patient and provider have in working together to achieve a desired therapeutic outcome- was used as the primary outcome measure, since it has been shown to be important in predicting outcomes across a wide range of health problems, including depression. In an evaluation of 139 hospital patients who interacted with the agent at the time of discharge, all patients, regardless of depressive symptoms, rated the agent very high on measures of satisfaction and ease of use, and most preferred receiving their discharge information from the agent compared to their doctors or nurses in the hospital. In addition, we found that patients with symptoms indicative of major depression rated the agent significantly higher on therapeutic alliance compared to patients who did not have major depressive symptoms. We conclude that empathic agents represent a promising technology for patient assessment, education and counseling for those most in need of comfort and caring in the inpatient setting.

Gender as risk factor for 30 days post-discharge hospital utilisation: a secondary data analysis

Objective In the 30 days after hospital discharge, hospital utilisation is common and costly. This study evaluated the association between gender and hospital utilisation within 30 days of discharge. Design Secondary data analysis using Poisson regression stratified by gender. Participants 737 English-speaking hospitalised adults from general medical service in urban, academic safety-net medical centre who participated in the Project Re-Engineered clinical trial (clinicaltrials.gov identifier: NCT00252057). Main outcome measure The primary end point was hospital utilisation, defined as total emergency department visits and hospital readmissions within 30 days after index discharge. Results Female subjects had a rate of 29 events for every 100 people and male subjects had a rate of 47 events for every 100 people (incident rate ratio (IRR) 1.62, 95% CI 1.28 to 2.06). Among men, risk factors included hospital utilisation in the 6 months prior to the index hospitalisation (IRR 3.55, 95% CI 2.38 to 5.29), being unmarried (IRR 1.72, 95% CI 1.12 to 2.64), having a positive depression screen (IRR 1.53, 95% CI 1.09 to 2.13) and no primary care physician (PCP) visit within 30 days (IRR 1.64, 95% CI 1.08 to 2.50). Among women, the only risk factor was hospital utilisation in the 6 months prior to the index hospitalisation (IRR 3.08, 95% CI 1.86 to 5.10). Conclusions In our data, male subjects had a higher rate of hospital utilisation within 30 days of discharge than female subjects. For men—but not for women—risk factors were being retired, unmarried, having depressive symptoms and having no PCP visit within 30 days. Interventions addressing these factors might lower hospital utilisation rates observed among men.

Dose‐response relationship between depressive symptoms and hospital readmission

BACKGROUND Evidence suggests depression increases hospital readmission risk. OBJECTIVE Determine whether depressive symptoms are associated with unplanned readmission within 30 days of discharge of general medical patients. DESIGN Secondary analysis of the Project Re-Engineered Discharge (RED) randomized controlled trials. SETTING Urban academic safety-net hospital. PATIENTS A total of 1418 hospitalized adult English-speaking patients. INTERVENTION The 9-Item Patient Health Questionnaire (PHQ-9) was used to screen patients for depressive symptoms. MEASUREMENTS Hospital readmission within 30 days of discharge. Poisson regression was used to control for confounding variables. RESULTS There were 225 (16%) patients who screened positive for mild depressive symptoms (5 ≤PHQ-9 ≤ 9) and 336 (24%) for moderate or severe depressive symptoms (PHQ-9 ≥ 10). After controlling for confounders, a higher rate of readmission was observed in subjects with mild depressive symptoms compared to subjects with PHQ-9 <5, incidence rate ratio (IRR) 1.49 (95% confidence interval [CI]: 1.11-2.00). The adjusted IRR of readmission for those with moderate-to-severe symptoms was 1.96 (95% CI: 1.51-2.49) compared to those with no depression. CONCLUSIONS Screening positive for mild and moderate-to-severe depressive symptoms during a hospitalization on a general medical service is associated with an increased dose-dependent readmission rate within 30 days of discharge in an urban, academic, safety-net hospital. Further research is needed to determine whether treatments targeting the reduction of depressive symptoms reduce the risk of readmission.

Reducing Preconception Risks Among African American Women with Conversational Agent Technology

Background: Systems and tools are needed to identify and mitigate preconception health (PCH) risks, particularly for African American (AA) women, given persistent health disparities. We developed and tested “Gabby,” an online preconception conversational agent system. Methods: One hundred nongravid AA women 18–34 years of age were screened for over 100 PCH risks and randomized to the Gabby or control group. The Gabby group interacted with the system for up to six months; the control group received a letter indicating their health risks with a recommendation to talk with their clinician. The numbers, proportions, and types of risks were compared between groups. Results: There were 23.7 (SD 5.9) risks identified per participant. Eighty-five percent (77 of 91) provided 6 month follow up data. The Gabby group had greater reductions in the number (8.3 vs. 5.5 risks, P < .05) and the proportion (27.8% vs 20.5%, P < 0.01) of risks compared to controls. The Gabby group averaged 63.7 minutes of interaction time. Seventy-eight percent reported that it “was easy to talk to Gabby” and 64% used information from Gabby to improve their health. Conclusion: Gabby was significantly associated with preconception risk reduction. More research is needed to determine if Gabby can benefit higher risk populations and if risk reduction is clinically significant.