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.

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.

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 .

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.

Effective strategies to improve the management of heart failure.

The purpose of this article is to provide resources for primary care physicians to manage heart failure as a chronic disease. We review evidence-based interventions that can be adopted in primary care practices to improve adherence to available guidelines for medication use, promotion of self-care behaviors, transitions of care in acute decompensated heart failure, and end of life care. This information will be valuable to primary care providers who care for patients with heart failure in all care settings but is focused on the management of heart failure in the outpatient setting.

Intracellular sodium determines frequency-dependent alterations in contractility in hypertrophied feline ventricular myocytes.

Hypertrophy and failure (H/F) in humans and large mammals are characterized by a change from a positive developed force-frequency relationship (+FFR) in normal myocardium to a flattened or negative developed force-frequency relationship (-FFR) in disease. Altered Ca(2+) homeostasis underlies this process, but the role of intracellular Na(+) concentration ([Na(+)](i)) in H/F and frequency-dependent contractility reserve is unclear. We hypothesized that altered [Na(+)](i) is central to the -FFR response in H/F feline myocytes. Aortic constriction caused left ventricular hypertrophy (LVH). We found that as pacing rate was increased, contraction magnitude was maintained in isolated control myocytes (CM) but decreased in LVH myocytes (LVH-M). Quiescent LVH-M had higher [Na(+)](i) than CM (LVH-M 13.3 +/- 0.3 vs. CM 8.9 +/- 0.2 mmol/l; P < 0.001) with 0.5-Hz pacing (LVH-M 14.9 +/- 0.5 vs. CM 10.8 +/- 0.4 mmol/l; P < 0.001) but were not different at 2.5 Hz (17.0 +/- 0.7 vs. control 16.0 +/- 0.7 mmol/l; not significant). [Na(+)](i) was altered by patch pipette dialysis to define the effect of [Na(+)](i) on contraction magnitude and action potential (AP) wave shape at slow and fast pacing rates. Using AP clamp, we showed that LVH-M require increased [Na(+)](i) and long diastolic intervals to maintain normal shortening. Finally, we determined the voltage dependence of contraction for Ca(2+) current (I(Ca))-triggered and Na(+)/Ca(2+) exchanger-mediated contractions and showed that there is a greater [Na(+)](i) dependence of contractility in LVH-M. These data show that increased [Na(+)](i) is essential for maintaining contractility at slow heart rates but contributes to small contractions at fast rates unless rate-dependent AP shortening is prevented, suggesting that altered [Na(+)](i) regulation is a critical contributor to abnormal contractility in disease.

Phosphorylation of phospholamban at threonine-17 reduces cardiac adrenergic contractile responsiveness in chronic pressure overload-induced hypertrophy.

Physiological hemodynamic stress, such as aerobic exercise, is intermittent and requires an increase in Ca2+ -dependent contractility through sympathetic nervous system activation. Pathological hemodynamic stress, such as hypertension, is persistent and requires sustained increases in cardiac function. Over time, this causes left ventricular hypertrophy (LVH)-reduced responsiveness to sympathetic stimulation. In this study, we examined the hypothesis that blunted in vivo adrenergic contractile responsiveness in pressure overload (PO)-induced cardiac hypertrophy is caused by abnormalities in the abundance and/or basal phosphorylation state of Ca2+ regulatory proteins. PO, induced by aortic constriction, caused concentric LVH or dilated LVH. Only animals with dilation exhibited a decrease in baseline left ventricle function [fractional area change (FAC); measured with echocardiography]. All PO animals had a reduced contractile response to adrenergic agonists (increase in FAC with 40 microg.kg(-1).min(-1) dobutamine, control 0.30 +/- 0.04, n = 5 vs. banded 0.10 +/- 0.03, n = 10; P < 0.01). PO animals had reduced phospholamban (PLB) protein abundance (P = 0.07, not significant) and increased PLB phosphorylation at the calmodulin-dependent kinase II (CaMKII)-specific site (PLB-Thr17, P < 0.05) but not at the protein kinase A-specific site (PLB-Ser16). PLB-Thr17 phosphorylation was inversely correlated with dobutamine-induced increases in contractility in PO animals (r2 = 0.81, P < 0.05). Continuous induction of Ca2+ transients in isolated ventricular myocytes for 24 h increased phosphorylation at PLB-Thr17 and diminished inotropic responsiveness and PLB-Ser16 phosphorylation after exposure to isoproterenol (P < 0.05). These data show that reduced adrenergic responsiveness in feline PO hypertrophy and failure involves increases in basal PLB-Thr17 phosphorylation, suggesting that activation of CaMKII in PO hypertrophy contributes to defective adrenergic reserve in compensated LVH and early heart failure.

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.

Pharmacological effects of ATI22-107 [2-(2-{2-[2-chloro-4-(6-oxo-1,4,5,6-tetrahydro-pyridazin-3-yl)-phenoxy]-acetylamino}-ethoxymethyl)-4-(2-chloro-phenyl)-6-methyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid dimethyl ester)], a novel dual pharmacophore, on myocyte calcium cycling and contractility.

Historically, inhibitors of type III phosphodiesterases (PDE-III) have been effective inotropes in mammalian myocardium, but their clinical utility has been limited by adverse events, including arrhythmias that are considered to be due to Ca(2+) overload. ATI22-107 [2-(2-{2-[2-chloro-4-(6-oxo-1,4,5,6-tetrahydro-pyridazin-3-yl)-phenoxy]-acetylamino}-ethoxymethyl)-4-(2-chlorophenyl)-6-methyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid dimethyl ester)], a novel, dual pharmacophore compound, was designed to simultaneously inhibit the cardiac phosphodiesterase (PDE-III) and produce inotropic effects, whereas inhibiting the L-type calcium channel (LTCC) was designed to minimize increases in diastolic Ca(2+). We compared the effects of ATI22-107 and enoximone, a pure PDE-III inhibitor, on the Fluo-3 calcium transient in normal feline ventricular myocytes and trabeculae. Enoximone-induced dose-dependent increases in peak [Ca(2+)](i), diastolic [Ca(2+)](i), T50, and T75. ATI22-107 demonstrated similar dose-dependent increases in peak [Ca(2+)](i) at 300 nM and 1.0 microM doses, with no further increases at higher doses. Throughout the dosing range, ATI22-107 induced much smaller, if any, increases in diastolic [Ca(2+)](i), T(25), and T(75). Current measurement of LTCC via patch-clamp techniques revealed dose-dependent decreases in LTCC current with an increasing dose of ATI22-107, thereby validating the dual functionality of the drug that has been proposed in this study. Studies in isolated trabeculae demonstrated that enoximone-induced a dose-dependent augmentation of the entire force-frequency relation in normal myocardium, whereas augmentation of contractility was only observed at lower stimulation frequencies with ATI22-107. These results demonstrate the effects of the LTCC-antagonizing moiety of ATI22-107 and suggest that the novel simultaneous combination of PDE-III and LTCC inhibition by one molecule may produce a favorable profile of limited inotropy without detrimental effects of increased diastolic [Ca(2+)](i).