"Once I take that one bite": the consideration of harm reduction as a strategy to support dietary change for patients with diabetes.

BACKGROUND: Despite well-established guidelines to treat diabetes, many people with diabetes struggle to manage their disease. For many, this struggle is related to challenges achieving nutrition-related lifestyle changes. We examined how people with diabetes describe barriers to maintaining a healthy diet and considered the benefits of using a harm reduction approach to assist patients to achieve nutrition-related goals. METHODS: This is a secondary analysis of 89 interviews conducted with adults who had type 1 or type 2 diabetes. Interviews were analyzed using a content analysis approach. Themes regarding food or diet were initially captured in a "food" node. Data in the food node were then sub-coded for this analysis, again using a content analysis approach. RESULTS: Participants frequently used addiction language to talk about their relationship with food, at times referring to themselves as "an addict" and describing food as "their drug." Participants perceived their unhealthy food choices either as a sign of weakness or as "cheating." They also identified food's ability to comfort them and an unwillingness to change as particular challenges to sustaining a healthier diet. CONCLUSION: Participants often described their relationship with food through an addiction lens. A harm reduction approach has been associated with positive outcomes among those with substance abuse disorder. Patient-centered communication incorporating the harm reduction model may improve the patient-clinician relationship and thus improve patient outcomes and quality-of-life while reducing health-related stigma in diabetes care. Future work should explore the effectiveness of this approach in patients with diabetes. TRIAL REGISTRATION: Registered on ClinicalTrials.gov, NCT02792777. Registration information submitted 02/06/2016, with the registration first posted on the ClinicalTrials.gov website 08/06/2016. Data collection began on 29/04/2016.

Patient and provider prediabetes knowledge, attitudes, and behavior in a large urban family medicine practice.

Context: One-third of American adults have prediabetes. However, only 11% are aware of their condition, and they often do not receive prediabetes education or management. Prior studies have indicated knowledge gaps among primary care providers and patients on prediabetes management. Objective: To understand family medicine providers' and patients' attitudes, knowledge, and behaviors regarding prediabetes and its management to inform a prediabetes management intervention. Study Design: Cross-sectional surveys. Setting: A large academic family medicine practice in downtown Philadelphia with 30,000 patients making 80,000 visits annually. Population studied: Family medicine providers (attending physicians, nurse practitioners, residents) and adult patients seen within the last year, with HbA1c in the last 6 months between 5.7-6.4% (excluding pregnant, diabetes diagnosis). Instruments: Provider survey asking demographics, knowledge, attitudes, management, DPP awareness, barriers to prediabetes treatment, and open-ended question on how the practice could improve prediabetes management. Patient survey asking demographics, awareness of diagnosis and risk, knowledge, attitudes, experiences with DPP, prediabetes experiences with PCP, and same open-ended question as provider survey. Provider survey distributed via email; patient survey via Epic MyChart patient portal. Outcome Measures: Descriptive statistics for all quantitative survey items; thematic analysis of open-ended responses. Results: Fifty-four providers and 148 patients completed the surveys (57% and 16.5% response rates, respectively). Nearly all providers (96%) felt that prediabetes screening and management is important but most (74%) prescribe metformin to ≤ 25% of eligible patients. Over half (56%) were unaware of DPP, and 52% of those aware of DPP did not know how to refer a patient. Over half (59%) of patients reported having been told they have prediabetes and 84% thought diet and lifestyle changes were effective treatment, but 65% were unaware of medication options and only 5% had been referred to DPP. In open-ended responses, providers requested more nutrition counseling and an improved DPP referral process; patients also requested nutrition counseling and classes. Conclusions: Providers and patients saw prediabetes as important but reported knowledge and management gaps, particularly for metformin and DPP, and requested additional practice resources.

Patient Markers of Successful Diabetes Management.

PURPOSE: For individuals with diabetes, diabetes health status may not align with A1C targets. Patients may use nonclinical targets when assessing their diabetes management success. Identifying these targets is important in developing patient-centered management plans. The purpose of this study was to identify patient markers of successful diabetes management among patients in an urban academic health system. METHODS: A secondary analysis of semistructured interviews was completed with 89 adults with type 1 or type 2 diabetes. Participants had a recent diabetes-related emergency department (ED) visits or hospitalization or were primary care patients with an A1C >7.5%. Interviews were conducted to saturation. Demographic data were collected via self-report and electronic medical records. Interviews were analyzed using conventional content analysis. This analysis focused on patient perceptions of successful management coded to "measuring management success." RESULTS: Although most participants cited A1C or blood glucose as a marker of successful diabetes management, they had varied understanding of these metrics. Most used a combination of targets from the following categories: 1) A1C, blood glucose, and numbers; 2) engagement in medical care; 3) taking medication and medication types; 4) symptoms; 5) diet, exercise, and weight; and 6) stress management and social support. CONCLUSION: Individuals not meeting glycemic goals and/or with recent diabetes-related ED visits or hospitalizations had varied understanding of A1C and blood glucose targets. They use multiple additional markers of successful management and had a desire for management discussions that incorporate these markers. These measures should be incorporated into their care plans along with clinical targets.

"I had no other choice but to catch it too": the roles of family history and experiences with diabetes in illness representations.

BACKGROUND: A family history of diabetes and family members' experiences with diabetes may influence individuals' beliefs and expectations about their own diabetes. No qualitative studies have explored the relationship between family history and experiences and individuals' diabetes illness representations. METHODS: Secondary data analysis of 89 exploratory, semi-structured interviews with adults with type 1 or type 2 diabetes seeking care in an urban health system. Participants had a recent diabetes-related ED visit/hospitalization or hemoglobin A1c > 7.5%. Interviews were conducted until thematic saturation was achieved. Demographic data were collected via self-report and electronic medical record review. Interviews were audio-recorded, transcribed, and coded using a conventional content analysis approach. References to family history and family members' experiences with diabetes were analyzed using selected domains of Leventhal's Common Sense Model of Self-Regulation. RESULTS: Participants cited both genetic and behavioral family history as a major cause of their diabetes. Stories of relatives' diabetes complications and death figured prominently in their discussion of consequences; however, participants felt controllability over diabetes through diet, physical activity, and other self-care behaviors. CONCLUSIONS: Findings supported an important role of family diabetes history and experience in development of diabetes illness representations. Further research is needed to expand our understanding of the relationships between these perceptions, self-management behaviors, and outcomes. Family practice providers, diabetes educators and other team members should consider expanding assessment of current family structure and support to also include an exploration of family history with diabetes, including which family members had diabetes, their self-care behaviors, and their outcomes, and how this history fits into the patient's illness representations.

The power of the group: comparison of interviews and group concept mapping for identifying patient-important outcomes of care.

BACKGROUND: Data are limited regarding how to effectively and efficiently identify patient priorities for research or clinical care. Our goal was to compare the comprehensiveness and efficiency of group concept mapping (GCM), a group participatory method, to interviews for identifying patient goals when seeking care. METHODS: We engaged patients with moderately- to poorly-controlled diabetes mellitus in either GCM or an individual interview. The primary outcome was the comprehensiveness of GCM brainstorming (the first stage of GCM) as compared to interviews for eliciting patient-important outcomes (PIOs) related to seeking care. Secondary outcomes included 1) comprehensiveness of GCM brainstorming and interviews compared to a master list of PIOs and 2) efficiency of GCM brainstorming, the entire GCM process and interviews. RESULTS: We engaged 89 interview participants and 52 GCM participants (across 3 iterations of GCM) to identify outcomes most important to patients when making decisions related to diabetes management. We identified 26 PIOs in interviews, 33 PIOs in the first GCM brainstorming session, and 38 PIOs across all three GCM brainstorming sessions. The initial GCM brainstorming session identified 77% (20/26) of interview PIOs, and all 3 GCM brainstorming sessions combined identified 88% (23/26). When comparing GCM brainstorming and interviews to the master list of PIOs, the initial GCM brainstorming sessions identified 80% (33/41), all 3 GCM brainstorming sessions identified 93% (38/41) and interviews identified 63% (26/41) of all PIOs. Compared to interviews, GCM brainstorming required less research team time, more patient time, and had a lowest cost. The entire GCM process still required less research team time than interviews, though required more patient time and had a higher cost than interviews. CONCLUSIONS: GCM brainstorming is a powerful tool for effectively and efficiently identifying PIOs in certain scenarios, though it does not provide the breadth and depth of individual interviews or the higher level conceptual organization of the complete process of GCM. Selection of the optimal method for patient engagement should include consideration of multiple factors including depth of patient input desired, research team expertise, resources, and the population to be engaged. TRIAL REGISTRATION: Registered on ClinicalTrials.gov , NCT02792777. Registration information submitted 6/2/2016, with the registration first posted on the ClinicalTrials.gov website 6/8/2016. Data collection began on 4/29/2016.

The effect of diabetes self-management education on HbA1c and quality of life in African-Americans: a systematic review and meta-analysis.

BACKGROUND: Type 2 diabetes presents a major morbidity and mortality burden in the United States. Diabetes self-management education (DSME) is an intervention associated with improved hemoglobin A1c(HbA1c) and quality of life(QOL), and is recommended for all individuals with type 2 diabetes. African-Americans have disproportionate type 2 diabetes morbidity and mortality, yet no prior meta-analyses have examined DSME outcomes exclusively in this population. This systematic review and meta-analysis examined the impact of DSME on HbA1c and QOL in African-Americans compared to usual care. METHODS: Randomized controlled trials, cluster-randomized trials, and quasi-experimental interventions were included. 352 citations were retrieved; 279 abstracts were reviewed, and 44 full-text articles were reviewed. Fourteen studies were eligible for systematic review and 8 for HbA1c meta-analysis; QOL measures were too heterogeneous to pool. Heterogeneity of HbA1c findings was assessed with Cochran's Q and I2. RESULTS: HbA1c weighted mean difference between intervention and usual care participants was not significant: - 0.08%[- 0.40-0.23];χ2 = 84.79 (p < .001), I2 = 92%, (n = 1630). Four of five studies measuring QOL reported significant improvements for intervention participants. CONCLUSIONS: Meta-analysis results showed non-significant effect of DSME on HbA1c in African-Americans. QOL did show improvement and is an important DSME outcome to measure in future trials. Further research is needed to understand effectiveness of DSME on HbA1c in this population. TRIAL REGISTRATION: PROSPERO registration: CRD42017057282 .

Concept Mapping as a Method to Engage Patients in Clinical Quality Improvement.

Patient engagement has become a primary care research and practice priority. Little guidance exists, however, on how best to engage patients in primary care practice improvement, or how to measure the impact of their engagement. We present an overview of group concept mapping as a method for engaging patients in primary care practice improvement. We detail the group concept mapping process as a tool for use in primary care practice improvement, research, and evaluation, and we present resources to enable researchers and practice leaders to use this tool in practice improvement. To illustrate the method, we present a practice-based quality improvement project conducted with patients and staff at a large urban academic primary care practice.

Evaluation of a Quality Improvement Experience for Family Medicine Clerkship Students.

BACKGROUND AND OBJECTIVES: There is emphasis on systems-based practice competencies and quality improvement (QI) training in postgraduate medical education. However, we lack effective approaches to provide experiences in these areas during undergraduate medical education. To address this, we developed a novel approach to providing didactic and experiential learning experiences in QI during a third-year family medicine clerkship. METHODS: We implemented and evaluated a QI curriculum combining self-directed learning with real-world experience to increase knowledge and confidence in the plan-do-study-act (PDSA) process for family medicine clerkship students. Students collaborated and presented their change ideas in a "Shark Tank" format for practice leaders at the end of their rotation. We used pre- and postcurriculum surveys to assess knowledge of and comfort with completing QI projects. RESULTS: Three hundred eighty-nine students completed precurriculum surveys and 242 completed postcurriculum surveys. Pre- and postlearning evaluations revealed an increase in agreement or strong agreement with self-reported understanding of specific QI topic areas of 50%. Almost all (91.3%) reported feeling confident or reasonably confident in their ability to create change in health care after exposure to the curriculum, compared with 66.3% in the precurriculum survey. One-third of students (34%) reported intent to complete the Institute for Healthcare Improvement Open School curriculum in QI. CONCLUSIONS: Self-directed learning about QI, combined with practice observation, small-group discussion and presentation in a Shark Tank format was effective and engaging for learners. Students had limited preexisting knowledge of QI principles, suggesting a need for preclinical exposure to this topic. The family medicine clerkship provides an ideal environment for teaching QI.

Association of Prediabetes Status Awareness With Behaviors and Perception of Health.

INTRODUCTION: Lifestyle modification can significantly reduce the risk of developing diabetes. However, the effect of prediabetes status awareness on perceptions of health and health behaviors are mixed. We used the 2015 to 2016 National Health and Nutrition Examination Survey (NHANES) data to evaluate the association of prediabetes status awareness with self-reported perception of health and health behaviors. METHODS: A secondary analysis was performed on the 2015 to 2016 NHANES, which is a biannual, cross-sectional survey designed to be representative of the civilian, noninstitutionalized United States population. Survey participants were interviewed at home and invited to a mobile examination center to undergo examinations and laboratory measurements. Inclusion and exclusion criteria were applied to create prediabetes-aware and prediabetes-unaware groups. The groups were propensity-score matched based on Body Mass Index, A1c, race, and education. Measures of health perception and health behaviors were analyzed, including feeling at risk for developing diabetes, general health status, perception of weight, desire to lose weight, dietary behaviors, and physical activity behaviors. RESULTS: Participants who were prediabetes aware were more likely to report a perceived risk of diabetes and to consider themselves overweight. Prediabetes awareness was not associated with any difference in dietary or physical activity behaviors. CONCLUSIONS: Although participants who were aware of their prediabetes status were more likely to report a perceived threat of developing diabetes, they did not report increased engagement in health behaviors. Future research can better understand how these aspects of a health belief model affect engagement in health behaviors for people with prediabetes.

Differences in Persistently Elevated Hemoglobin A1c for African American and White Patients and the Role of Provider-Level Variation.

African Americans with type 2 diabetes (T2D) have higher average A1c levels than White patients. However, few studies have examined racial disparities in diabetes management in primary care, particularly provider-level variability. Study goals were to analyze racial differences for patients with any/2 or more elevated A1cs, explore patterns of visits/providers seen in patients with ≥1 elevated A1c, and explore the contributions of provider variability in patient A1c. A retrospective secondary analysis of electronic medical record data from a large urban health system was conducted, involving adult African American or White patients (ages18-65 years) with ≥2 measured A1cs between January 1, 2017-February 1, 2018. Descriptive statistics were calculated for demographic variables; paired t tests evaluated changes in A1c levels across the 2 most recent measurements, and a repeated measures ANOVA evaluated the impact of race on A1c changes. Logistic regression analyses examined the relationship of race with any elevated A1c levels and persistent A1c levels (≥ 2 consecutive A1c measurements ≥8.5). The intraclass correlation coefficient (ICC) estimated clustering of A1c by provider. A total of 1764 patients were included. African Americans were more likely to have any (odds ratio [OR] = 1.48, P < .001) and persistently elevated A1c (OR = 1.75, P = .0003). ICC was .27 for any elevated A1c and .32 for persistently elevated A1c. In primary care patients with T2D, African Americans were more likely than Whites to have any/persistently elevated A1c, with substantial variability attributable to the provider. Further research is needed to better understand patient- and provider-level contributors to A1c disparities.

Critical Race Theory as a Lens for Examining Primary Care Provider Responses to Persistently-Elevated HbA1c.

INTRODUCTION: Clinical inertia remains a persistent problem in the treatment of diabetes in clinical care. Primary care provider behavior is thought to be a significant contributor to diabetes clinical inertia. This study used the lens of Critical Race Theory to examine whether provider's diabetes management activities differ by patient race and frame implications for future research. METHODS: Chart abstractors retrospectively reviewed a random sample of charts from primary care patients with persistently-elevated HbA1c to assess providers' diabetes management activities in the subsequent year. Provider activities aligned with the American Diabetes Association's standards of medical care and included HbA1c test ordering, documentation of patient medication adherence, counseling on lifestyle modification, lifestyle modification referral, endocrinologist participation in care, and medication titration. Differences in provider actions by patient race (Black, white, or other) were examined using chi-square tests. RESULTS: A total of 188 patient charts were reviewed. For all provider actions, there were statistically-significant differences by patient race. Black patients were least likely to be counseled on dietary changes (72.0%) or physical activity (57.7%) by their primary care provider, but most likely to be referred to an outside specialist for this counseling (46.2%). Black patients were also least likely to have medication adjustments made (72%). DISCUSSION: Study findings showed an association between provider diabetes management behaviors and patient race, Future studies showed explore providers' racial beliefs, attitudes and clinical decision-making, and patients' experiences with historical exclusion from medical care and racism in healthcare encounters In addition, more research is needed to explore the role of structural racism in clinical inertia.

Patient-important outcomes to inform shared decision making and goal setting for diabetes treatment.

OBJECTIVE: Despite well-established treatment guidelines, diabetes is difficult to manage for many individuals. The importance of using shared decision making to optimize diabetes treatment is recognized, yet what matters most to individuals with diabetes is not well established. Our goal was to identify patients' goals and priorities for diabetes management. METHODS: We engaged 141 participants through interviews and group concept mapping to identify patient-important outcomes (PIOs) for diabetes care. We generated a master list of PIOs by aggregating interview data coded to "goals" and ideas brainstormed during concept mapping, and then a patient advisory board sorted the PIOs into higher-level domains. RESULTS: We identified 41 PIOs sorted into 7 broad domains: optimize daily self-care, optimize long term health, learn about diabetes, achieve measurable goals, manage medications, manage diet and best utilize medical / professional services. CONCLUSIONS: Most (4/7) of PIO domains focused on personal and life goals, not medically-oriented goals. Use of these PIOs and domains may facilitate more effective SDM discussions for patients with diabetes. PRACTICE IMPLICATIONS: Use of PIOs from this work can enable the empowerment of patients to voice their priorities during SDM conversations, thus facilitating development of truly individualized diabetes treatment plans.

Assessing the impact of medically tailored meals and medical nutrition therapy on type 2 diabetes: Protocol for Project MiNT.

BACKGROUND: Research has shown that among people with type 2 diabetes mellitus, reduction in hemoglobin A1c (HbA1c) prevents long term complications. Medically tailored meals (MTM) and telehealth-delivered medical nutrition therapy (tele-MNT) are promising strategies for patient-centered diabetes care. OBJECTIVES: Project MiNT will determine whether provision of MTM with and without the addition of telehealth-delivered medical nutrition therapy improves HbA1c and is cost effective for patients with type 2 diabetes mellitus. METHODS: Patients with poorly controlled type 2 diabetes mellitus (HbA1c >8%) will be recruited from Jefferson Health. Eligible patients will be randomized to one of three arms: 1) usual care, 2) 12 weeks of home-delivered MTM, or 3) MTM + 12 months of tele-MNT. All participants (n = 600) will complete three follow-up assessments at 3, 6, and 12 months. The primary outcome is change in HbA1c at 6 months. Secondary outcomes include change in HbA1c at 3 and 12 months and cost-effectiveness of the intervention at 6 and 12 months. Conclusion Findings from Project MiNT will inform MTM coverage and financing decisions, how to structure services for scalability and system-wide integration, and the role of these services in reducing health disparities.

Organizational Readiness to Change: Quality Improvement in Family Medicine Residency.

INTRODUCTION: Primary care is evolving to meet greater demands for the inclusion of collaborative health care quality improvement (QI) processes at the practice level. Yet, data on organizational preparedness for change are limited. We assessed the feasibility of incorporating an organizational-level readiness-to-change tool that identifies factors relevant to QI implementation at the practice level impacting new family medicine physicians. METHODS: We assessed organizational readiness to change at the practice level among residents participating in a team-based QI training curriculum from April 2016 to April 2019. Seventy-six current and former residents annually completed the modified Organizational Readiness to Change Assessment (ORCA) survey. We evaluated QI and leadership readiness among five subscales: empowerment, management, QI, QI leadership (skills), and QI leadership (ability). We calculated mean survey scores and compared across all 3 years. Resident interviews captured unique perspectives and experiences with team-based activities. Qualitative analysis identified emergent themes. RESULTS: Residents completed 73 modified ORCA surveys (96% response rate). Compared to years 2016-2019, 2018 results were highest in mean negative responses for the QI subscale (24.62, SD 6.70). Four volunteers completed postsurvey interviews. Qualitative analysis identified issues concerning communication, team collaboration, practice site functioning, and survey relevance. CONCLUSIONS: Our study determined that miscommunication and practice site disruptions undermine organizational-level readiness to change, as measured by the ORCA tool which was part of a multimethod assessment included within a team-based QI training curriculum. Training programs undergoing curricula transformations may feasibly incorporate ORCA as a tool to identify impediments to collaborative practice and inform resource allocation important for enhancing physician training in QI leadership.

Patient experience and challenges in group concept mapping for clinical research.

BACKGROUND AND OBJECTIVE: Group concept mapping (GCM) is a research method that engages stakeholders in generating, structuring and representing ideas around a specific topic or question. GCM has been used with patients to answer questions related to health and disease but little is known about the patient experience as a participant in the process. This paper explores the patient experience participating in GCM as assessed with direct observation and surveys of participants. METHODS: This is a secondary analysis performed within a larger study in which 3 GCM iterations were performed to engage patients in identifying patient-important outcomes for diabetes care. Researchers tracked the frequency and type of assistance required by each participant to complete the sorting and rating steps of GCM. In addition, a 17-question patient experience survey was administered over the telephone to the participants after they had completed the GCM process. Survey questions asked about the personal impact of participating in GCM and the ease of various steps of the GCM process. RESULTS: Researchers helped patients 92 times during the 3 GCM iterations, most commonly to address software and computer literacy issues, but also with the sorting phase itself. Of the 52 GCM participants, 40 completed the post-GCM survey. Respondents averaged 56 years of age, were 50% female and had an average hemoglobin A1c of 9.1%. Ninety-two percent (n = 37) of respondents felt that they had contributed something important to this research project and 90% (n = 36) agreed or strongly agreed that their efforts would help others with diabetes. Respondents reported that the brainstorming session was less difficult when compared with sorting and rating of statements. DISCUSSION: Our results suggest that patients find value in participating in GCM. Patients reported less comfort with the sorting step of GCM when compared with brainstorming, an observation that correlates with our observations from the GCM sessions. Researchers should consider using paper sorting methods and objective measures of sorting quality when using GCM in patient-engaged research to improve the patient experience and concept map quality.

Eliciting patient-important outcomes through group brainstorming: when is saturation reached?

PURPOSE: Group brainstorming is a technique for the elicitation of patient input that has many potential uses, however no data demonstrate concept saturation. In this study we explore concept saturation in group brainstorming performed in a single session as compared to two or three sessions. METHODS: Fifty-two predominately African American adults patients with moderately to poorly controlled Diabetes Mellitus participated in three separate group brainstorming sessions as part of a PCORI-funded group concept mapping study examining comparing methods for the elicitation of patient important outcomes (PIOs). Brainstorming was unstructured, in response to a prompt designed to elicit PIOs in diabetes care. We combined similar brainstormed responses from all three sessions into a 'master list' of unique PIOs, and then compared the proportion obtained at each individual session, as well as those obtained in combinations of 2 sessions, to the master list. RESULTS: Twenty-four participants generated 85 responses in session A, 14 participants generated 63 in session B, and 14 participants generated 47 in session C. Compared to the master list, the individual sessions contributed 87%, 76%, and 63% of PIOs. Session B added 3 unique PIOs not present in session A, and session C added 2 PIOs not present in either A or B. No single session achieved >90% saturation of the master list, but all 3 combinations of 2 sessions achieved > 90%. CONCLUSIONS: Single sessions elicited only 63-87% of the patient-important outcomes obtained across all three sessions, however all combinations of two sessions elicited over 90% of the master list, suggesting that 2 sessions are sufficient for concept saturation. TRIAL REGISTRATION: NCT02792777 . Registered 2 June 2016.

Ca2+ influx-induced sarcoplasmic reticulum Ca2+ overload causes mitochondrial-dependent apoptosis in ventricular myocytes.

Increases in Ca2+ influx through the L-type Ca2+ channel (LTCC, Cav1.2) augment sarcoplasmic reticulum (SR) Ca2+ loading and the amplitude of the cytosolic Ca2+ transient to enhance cardiac myocyte contractility. Our hypothesis is that persistent increases in Ca2+ influx through the LTCC cause apoptosis if the excessive influx results in SR Ca2+ overload. Feline ventricular myocytes (VMs) in primary culture were infected with either an adenovirus (Ad) containing a rat Cav1.2 beta2a subunit-green fluorescent protein (GFP) fusion gene (Adbeta2a) to increase Ca2+ influx or with AdGFP as a control. Significantly fewer beta2a-VMs (21.4+/-5.6%) than GFP-VMs (99.6+/-1.7%) were viable at 96 hours. A fraction of beta2a-VMs (20.8+/-1.8%) contracted spontaneously (SC-beta2a-VMs), and viability was significantly correlated with the percentage of SC-beta2a-VMs. Higher percentages of apoptotic nuclei, DNA laddering, and cytochrome C release were detected in beta2a-VMs. This apoptosis was prevented with pancaspase or caspase-3 or caspase-9 inhibitors. L-type calcium current (I(Ca-L)) density was greater in beta2a-VMs (23.4+/-2.8 pA/pF) than in GFP-VMs (7.6+/-1.6 pA/pF). SC-beta2a-VMs had higher diastolic intracellular Ca2+ (Indo-1 ratio: 1.1+/-0.1 versus 0.7+/-0.03, P<0.05) and systolic Ca2+ transients (1.89+/-0.27 versus 0.80+/-0.08) than GFP-VMs. Inhibitors of Ca2+ influx, SR Ca2+ uptake and release, mitochondrial Ca2+ uptake, mitochondrial permeation transition pore, calpain, and Bcl-2-associated X protein protected beta2a-VMs from apoptosis. These results show that persistent increases in Ca2+ influx through the I(Ca-L) enhance contractility but lead to apoptosis through a mitochondrial death pathway if SR Ca2+ overload is induced.

Alterations in early action potential repolarization causes localized failure of sarcoplasmic reticulum Ca2+ release.

Depressed contractility of failing myocytes involves a decreased rate of rise of the Ca2+ transient. Synchronization of Ca2+ release from the junctional sarcoplasmic reticulum (SR) is responsible for the rapid rise of the normal Ca2+ transient. This study examined the idea that spatially and temporally dyssynchronous SR Ca2+ release slows the rise of the cytosolic Ca2+ transient in failing feline myocytes. Left ventricular hypertrophy (LVH) with and without heart failure (HF) was induced in felines by constricting the ascending aorta. Ca2+ transients were measured in ventricular myocytes using confocal line scan imaging. Ca2+ transients were induced by field stimulation, square wave voltage steps, or action potential (AP) voltage clamp. SR Ca2+ release was significantly less well spatially and temporally synchronized in field-stimulated HF versus control or LVH myocytes. Surprisingly, depolarization of HF cells to potentials where Ca2+ currents (ICa) were maximal resynchronized SR Ca2+ release. Correspondingly, decreases in the amplitude of ICa desynchronized SR Ca2+ release in control, LVH, and HF myocytes to the same extent. HF myocytes had significant loss of phase 1 AP repolarization and smaller ICa density, which should both reduce Ca2+ influx. When normal myocytes were voltage clamped with HF AP profiles SR Ca2+ release was desynchronized. SR Ca2+ release becomes dyssynchronized in failing feline ventricular myocytes because of reductions in Ca2+ influx induced in part by alterations in early repolarization of the AP. Therefore, therapies that restore normal early repolarization should improve the contractility of the failing heart.

What family physicians can do to combat bullying.

Bullying has significant health implications for young people and society at large. These screening tools, tips for responding to bullies, and Web resources can help.

Implementation of Technology-based Patient Engagement Strategies within Practice-based Research Networks.

BACKGROUND: Technology-based patient engagement strategies (such as patient portals) are increasingly available, yet little is known about current use and barriers within practice-based research networks (PBRNs). PBRN directors have unique opportunities to inform the implementation of patient-facing technology and to translate these findings into practice. METHODS: PBRN directors were queried regarding technology-based patient engagement strategies as part of the 2015 CAFM Educational Research Alliance (CERA) survey of PBRN directors. A total of 102 PBRN directors were identified via the Agency for Healthcare Research and Quality's registry; 54 of 96 eligible PBRN directors completed the survey, for a response rate of 56%. RESULTS: Use of technology-based patient engagement strategies within PBRNs was limited, with less than half of respondents reporting experience with the most frequently named tools (risk assessments/decision aids). Information technology (IT) support was the top barrier, followed by low rates of portal enrollment. For engaging participant practices, workload and practice leadership were cited as most important, with fewer respondents noting concerns about patient privacy. DISCUSSION: Given limited use of patient-facing technologies, PBRNs have an opportunity to clarify the optimal use of these strategies. Providing IT support and addressing clinician concerns regarding workload may facilitate the inclusion of innovative technologies in PBRNs.