Doyle M. Cummings

Feasibility and Effectiveness of System Redesign for Diabetes Care Management in Rural Areas The Eastern North Carolina Experience

Purpose Redesigning the system of care for the management of patients with type 2 diabetes mellitus has not been well studied in rural communities with a significant minority population and limited health care resources. This study assesses the feasibility and potential for cost-effectiveness of restructuring care in rural fee-for-service practices for predominantly minority patients with diabetes mellitus. Methods This was a feasibility study of implementing case management, group visits, and electronic registry in 5 solo or small group primary care practices in rural North Carolina. The subjects were 314 patients with type 2 diabetes mellitus (mean age = 61 years; 72% African American; 54% female). An advanced practice nurse visited each practice weekly for 12 months, provided intensive diabetes case management, and facilitated a 4-session group visit educational program. An electronic diabetes registry and visit reminder systems were implemented. Results There was an improvement in the percentage of patients achieving diabetes management goals and an improvement in productivity and billable encounters. The percentage of patients with a documented self-management goal increased from 0% to 42%, a currently documented lipid panel from 55% to 76%, currently documented aspirin use from 25% to 37%, and currently documented foot examination from 12% to 54%. The average daily encounter rate improved from 20.17 to 31.55 on intervention days. Conclusions A redesigned care delivery system that uses case management with structured group visits and an electronic registry can be successfully incorporated into rural primary care practices and appears to significantly improve both care processes and practice productivity.

The efficacy and safety of DPP4 inhibitors compared to sulfonylureas as add-on therapy to metformin in patients with Type 2 diabetes: A systematic review and meta-analysis

There is no consensus on the selection of specific drug therapies when metformin fails in Type 2 diabetes (T2D). This meta-analysis was performed to determine the efficacy and safety of Dipeptidyl peptidase-4 inhibitors (DPP4-I) compared to sulfonylurea (SU) as add-on therapy to metformin in inadequately controlled T2D patients. We searched MEDLINE, CENTRAL, EMBASE, and CINAHL for randomized trials comparing DPP4-I to SU as add-on therapy to metformin and reported a change in hemoglobin A1c (HbA1c). Sixteen articles were included. There was a significantly greater reduction in HbA1c from baseline to 12 weeks with SU versus DPP4-I (MD[95% CI]=0.21%(2 mmol/mol) [0.06, 0.35]) but no significant difference at 52 and 104 weeks (MD[95% CI]=0.06%(-1 mmol/mol) [-0.03, 0.15] and 0.02%(-1 mmol/mol) [-0.13,0.18] respectively). SU was associated with weight gain and DPP4-I with weight loss at all time-points. The incidence of hypoglycemia at 12, 52, and 104 weeks was significantly greater with SU (20%, 24%, and 27% respectively) compared to DPP4-I (6%, 3%, and 4% respectively). The proportion of patients with HbA1c<7%(53 mmol/mol) without hypoglycemia was significantly higher at 52 and 104 weeks among patients on DPP4-I (RR[95% CI]=1.20 [1.05, 1.37] and 1.53 [1.16, 2.02] respectively). There was no significant difference between the two groups in the incidence of other side effects. While both SU and DPP4-I can be considered as options for add-on therapy to metformin in inadequately controlled T2D, SU results in a significantly increased risk of hypoglycemia and weight gain. By contrast, DPP4-I produce 0.4-0.6% (4-7 mmol/mol) reduction in HbA1c, lower risk of hypoglycemia, and weight loss.

Influence of Digoxin Immune Fab Therapy and Renal Dysfunction on the Disposition of Total and Free Digoxin

Digitalis intoxication occurs frequently and, in severe cases, administration of digoxin Fab antibodies (Fab) as an antidote may be warranted [1-5]. Fab is a specific antidote that quickly and effectively removes digoxin from the body and can save lives in patients with digoxin toxicity. Fab is obtained from the serum of sheep that have been immunized with digoxin molecules coupled to an antigenic hapten. It is a protein with a smaller molecular mass, less antigenicity, greater distribution volume, and a faster elimination than its parent IgG antibody. Because Fab has a high affinity for digoxin, it quickly removes it from its pharmacologically active binding site within tissue (adenosine triphosphatase) and sequesters it in the extracellular fluid [6, 7]. Hence, the signs and symptoms of digitalis intoxication are reversed within minutes. The concentration-time profile of total digoxin following administration of Fab is dependent on the disposition of Fab because most of the total digoxin is bound to it [4, 8-11]. Minutes after Fab is administered, the total (bound and free) serum digoxin concentration increases 10 to 30 times and the free state of digoxin in plasma decreases from approximately 75% to 90% to 0% to 5% [4, 5, 8-18]. When total digoxin reaches a maximum concentration after Fab administration, the plasma concentrations decline in a two-phase fashion; the initial phase probably represents both plasma elimination and the distribution of free and Fab-bound digoxin out of vascular spaces. The second phase represents terminal plasma elimination, which has a half-life ranging from 16 to 30 hours in patients with normal renal function [4, 8, 10, 15]. Free digoxin, on the other hand, decreases rapidly after Fab administration and then increases or rebounds. The rebound in free digoxin peaks approximately 3 to 24 hours after Fab administration (in patients with normal renal function) and then declines more slowly at a rate dependent on Fab and renal and nonrenal routes of elimination [4, 8, 10]. Renal dysfunction is expected to alter the disposition of Fab and total and free digoxin because digoxin and Fab are eliminated through renal excretion. Case reports suggest that renal dysfunction prolongs the terminal elimination half-lives of both Fab and total digoxin and may delay the rebound in free digoxin [11, 12, 14, 19]. Because digoxin that is bound to Fab is pharmacologically inactive, the free digoxin concentrations are more important predictors of pharmacologic activity, but only a few case reports describe their use during Fab therapy [9, 16]. Monitoring free digoxin in selected digoxin-toxic patients receiving Fab therapy may be warranted to confirm suspected reintoxication, to assess the necessity and amount of supplemental Fab doses, and to determine the timing of subsequent digoxin therapy. The aims of our study were to characterize the disposition of total and free digoxin following the administration of Fab in patients with varying degrees of renal function and to describe the potential utility of monitoring free digoxin concentrations. Methods Patients at Hartford Hospital (Hartford, Connecticut) and Henry Ford Hospital (Detroit, Michigan) who presented within the 18-month study period with clinical digoxin toxicity (as determined by their primary physician) were considered for entry into the study. Digoxin toxicity was defined by electrocardiographic changes; clinical symptoms such as nausea, vomiting, and central nervous system disturbances; and a digoxin concentration greater than 3.2 nmol/mL. Patients who received a Fab dose that was 50% or less than the recommended dose were excluded [20]. The study was approved by the institutional review committees of the participating institutions, and all patients gave written informed consent. After Fab was administered, serial blood samples were drawn (before hemodialysis if applicable). In most cases, if the initial serum creatinine level was 221 mol/L or less, blood was drawn every 12 hours for 72 hours; if the initial serum creatinine level was greater than 221 mol/L, blood was drawn every 24 hours until the patient was discharged from the hospital [21]. All samples were analyzed after patients had been treated and discharged. Sample Analysis A baseline digoxin concentration was obtained at the time that digoxin toxicity was suspected, at least 4 hours after the last digoxin dose. These samples were analyzed by the digoxin assays available at the study institutions (radioimmunoassay and Baxter Dade Stratus) and reflected total digoxin concentrations (total digoxin concentrations in the absence of Fab resemble those of free digoxin) [13, 16]. Samples collected for this study were assayed by two systems that have been previously described [11, 18, 21, 22]. Most patient blood samples (n = 12) were analyzed by a fluorescence polarization immunoassay (TDx, Digoxin II, Abbott Laboratories Diagnostic Division; Irving, Texas), and samples from patients 8 and 9 were analyzed using a modified immunofluorometric assay (Pharmacia Diagnostics, Fairfield, New Jersey). Data Analysis Pharmacokinetic parameters of free digoxin (maximum rebound, initial nadir, time to maximum rebound, mean maximum free fraction, and time to maximum free fraction) were determined by inspecting the digoxin concentration-time curve or free fraction-time curve. Total digoxin concentration-time data from the maximum total digoxin concentration observed following Fab therapy to the last data point obtained were fitted by nonlinear least-squares regression computed with PCNONLIN (Statistical Consultants; Lexington, Kentucky). The parameters estimated were elimination rate constants of the first and second phases of the total digoxin concentration-time profile, and , respectively, which were used to calculate the and phase half-lives, respectively. These parameters were poorly estimated in four patients (1, 2, 4, and 9) because the number of data points was insufficient, and therefore we have not reported them. Maximum and minimum values of total digoxin after Fab were determined by inspection of the concentration time curve. Data are reported as mean standard deviation. Results Patient Demographic Characteristics and Clinical Presentation Fourteen patients with suspected digoxin toxicity requiring Fab treatment were enrolled in the study (Table 1). Four patients had end-stage renal disease and were receiving chronic hemodialysis (patients 3, 9, 10, and 12), one had acute renal failure (patient 11), and the others had varying degrees of renal dysfunction (Table 1). Nine of the 14 patients had severe signs of digoxin toxicity (complete heart block or severe bradycardia [heart rate < 50 beats/min] or both with or without hemodynamic instability [n = 8] or hemodynamic instability [systolic blood pressure <100 mm Hg] only [n = 1]). Toxicity developed in 11 patients with chronic digoxin therapy, whereas 3 patients (patients 7, 12, and 13) became toxic shortly after they began digoxin therapy. Table 1. Patient Characteristics and Laboratory Values at Admission* Pharmacokinetics of Digoxin following Fab Administration Total digoxin concentrations ranged from 3.4 to 10.5 nmol/mL before Fab therapy. Following treatment with Fab, total digoxin levels increased rapidly, reaching a mean maximum concentration of 51.8 22.7 nmol/mL within 24 hours Figure 1, which were 9.6 5.8 times greater than the concentrations before Fab administration. Subsequently, total digoxin concentrations decreased in a two-phase fashion to a mean of 7.2 4.7 nmol/mL (Figure 1). The mean half-life of the initial phase of the total digoxin elimination curve () was 11.6 4.1 hours, whereas the half-life in the terminal elimination phase () was 118 57 hours. The elimination half-life values in patients with end-stage renal disease were longer than those in the other patients, 123 18 compared with 112 68 hours, respectively. Free digoxin following Fab therapy, on the other hand, decreased rapidly to a mean nadir of 0.62 1.1 nmol/mL, which was observed at the first sampling time, 7 to 24 hours after administration of the antidote. Subsequently, free digoxin increased in all patients (except patient 11) to an average maximum concentration of 1.7 1.3 nmol/mL, which occurred 77 46 hours (range, 23 to 192 hours) after Fab therapy. The time to maximum free digoxin rebound, however, occurred later in patients with end-stage renal disease compared with the other patients (127 40 hours compared with 55 28 hours, respectively). The magnitude of the maximum free digoxin rebound, however, was similar between patients with and without end-stage renal disease (1.79 0.96 compared with 1.61 1.41 nmol/mL, respectively). The free fraction of digoxin after Fab therapy also decreased quickly to approximately 0% in most patients, but then increased to a mean maximum of 18.2% 10%. Figure 1. Disposition of free and total digoxin time profiles. open circles closed circles Pharmacodynamics of Digoxin after Fab Therapy After Fab therapy, all patients had partial or complete resolution of their signs and symptoms of digoxin toxicity (see Table 1), which appeared to be temporally related to the decline in free digoxin. Fab therapy reversed the therapeutic benefits of digoxin in five patients [patients 1, 3, 5, 10, and 12]. These patients experienced relapses of their underlying conditions: four patients had a rapid ventricular response to atrial fibrillation 24 to 72 hours after Fab therapy, and patient 10 had an exacerbation of congestive heart failure and pulmonary edema 24 to 48 hours after Fab therapy. Atrial fibrillation in patient 12 was treated by reinitiating digoxin therapy approximately 48 hours after Fab treatment, resulting in a dramatic increase in the free digoxin concentration (from 0.65 nmol/mL 40 hours following Fab therapy to 2.7 nmol/mL 68 hours after Fab therapy) and control of the rapid ventricular response (see Figure 1). Three patients

Combining serum biomarkers: the association of C-reactive protein, insulin sensitivity, and homocysteine with cardiovascular disease history in the general US population

Background Elevated levels of serum biomarkers such as C-reactive protein (CRP) and homocysteine have been independently associated with cardiovascular risk. However, the prevalence of concurrent elevations of these biomarkers in the general population is unknown, as is their association with cardiovascular disease (CVD). Methods Data from adults (n = 4900) in the National Health and Nutrition Examination Survey were used to investigate the relationship between combinations of serum biomarkers of inflammation (CRP), atherosclerosis (homocysteine), and insulin sensitivity [homeostatic model assessment (HOMA) fasting insulin] and CVD. Using SUDAAN, logistic regression models were constructed to examine the relationships between elevated serum biomarkers (CRP, homocysteine, HOMA, or insulin), singly or in combination, and having a history of heart failure, myocardial infarction (MI), stroke, or any CVD, while controlling for age, race, sex, obesity, smoking, cholesterol level, diabetes history, hypertension history, exercise level, and dietary fiber intake. Results After adjustment for covariates, there was a significant relationship between concomitant elevations of CRP plus homocysteine and a history of MI [odds ratio (OR) 2.21], heart failure (OR 2.14), and any CVD (OR 1.87) that was stronger than the relationship between individual biomarkers alone and a history of CVD. In addition, combinations of elevated CRP plus HOMA and CRP plus insulin, remained significantly related to having a history of any CVD. Conclusion Recent scientific evidence and the present findings demonstrate the possibility for improving cardiovascular risk stratification through the concurrent evaluation of multiple biomarkers. In particular, these findings demonstrate the need to evaluate the combination of CRP and homocysteine prospectively as predictors of CVD.

Outpatient Colonoscopy by Rural Family Physicians

PURPOSE Five percent of family physicians offer colonoscopy services, either in the office or the hospital, often in rural areas that have no gastroenterologist. Two previous large series have shown the quality and safety of colonoscopy performed by family physicians. The purpose of this study was to verify these findings in an outpatient setting, as well as to obtain patient satisfaction data. METHODS Data were obtained from 731 colonoscopies performed between 1996 and 2001 in a rural Virginia family practice. These data included patients’ age and sex, indications for the procedure, drug dosages for sedation, cecal intubation rates, pathologic findings, complications, and referral correlation findings compared with the original examimation. A patient satisfaction survey was done. RESULTS The adenoma detection rate was 27.2% for men and 21.4% for women older than age 50 years. Six adenocarcinomas and 5 large (>2 cm) villous adenomas were detected, and the patients were referred for definitive surgical resection. A total of 29 patients (4%) were referred: 10 to colorectal surgery and 19 to gastroenterology for resection of large polyps. Correlation of findings at referral with the initial examination was excellent. Cecal intubation rates increased from 89.5% from 1996–1998 to 94.6% from 1999–2001. Minor sedation complications occurred in 5 cases (<1%), and patients responded to supportive care. A high degree of satisfaction was reported by patients, with a mean satisfaction score of 8.8 on a scale from 1 to 10. CONCLUSIONS Colonoscopy can be performed safely and competently by properly trained family physicians in an outpatient setting with a high degree of patient satisfaction.

Disposition of digoxin immune fab in patients with kidney failure

Digoxin and digoxin immune Fab, its antidote, are eliminated renally. However, the disposition of Fab in severe kidney disease is poorly described. Therefore, the disposition of Fab and its relationship to total and free digoxin were studied in five digoxin‐toxic patients with end‐stage renal disease (n = 4) or severe renal dysfunction (n = 1) with a mean (±SD) serum creatinine of 5.9 ± 1.2 mg/dl (four patients were receiving long‐term hemodialysis). Serum was drawn after a clinically neutralizing Fab dose (80 to 160 mg) every 12 to 24 hours for 204 to 327 hours. Fab concentrations were assessed by radioimmunoassay, whereas total digoxin concentrations were assessed with a modified radioimmunoassay or fluorescence polarization immunoassay. The concentration‐time profile of Fab appeared to be similar to the concentration‐time profile of total digoxin. The mean (±SD) half‐lives of the α and β disposition phases of Fab were 13 ± 5 hours and 96 ± 31 hours, respectively, which were similar to the α and β parameter estimates of total digoxin (14 ± 4 and 123 ± 16 hours, respectively). Steady‐state volume of distribution and systemic clearance of Fab were 0.29 ±0.11 L/kg and 0.057 ± 0.022 ml/min/kg, respectively. Thus, in comparison to values reported in patients with normal renal function, the elimination of Fab and total digoxin are markedly delayed in patients with end‐stage renal disease, which may necessitate prolonged clinical monitoring.

Consequences of Comorbidity of Elevated Stress and/or Depressive Symptoms and Incident Cardiovascular Outcomes in Diabetes: Results From the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study

OBJECTIVE To evaluate the impact of comorbid depressive symptoms and/or stress on adverse cardiovascular (CV) outcomes in individuals with diabetes compared with those without diabetes. RESEARCH DESIGN AND METHODS Investigators examined the relationship between baseline depressive symptoms and/or stress in adults with and without diabetes and physician-adjudicated incident CV outcomes including stroke, myocardial infarction/acute coronary heart disease, and CV death over a median follow-up of 5.95 years in the national REGARDS cohort study. RESULTS Subjects included 22,003 adults (4,090 with diabetes) (mean age 64 years, 58% female, 42% black, and 56% living in the southeastern “Stroke Belt”). Elevated stress and/or depressive symptoms were more common in subjects with diabetes (36.8% vs. 29.5%; P < 0.001). In fully adjusted models, reporting either elevated stress or depressive symptoms was associated with a significantly increased incidence of stroke (HR 1.57 [95% CI 1.05, 2.33] vs. 1.01 [0.79, 1.30]) and CV death (1.53 [1.08, 2.17] vs. 1.12 [0.90, 1.38]) in subjects with diabetes but not in those without diabetes. The combination of both elevated stress and depressive symptoms in subjects with diabetes was associated with a higher incidence of CV death (2.15 [1.33, 3.47]) than either behavioral comorbidity alone (1.53 [1.08, 2.17]) and higher than in those with both elevated stress and depressive symptoms but without diabetes (1.27 [0.86, 1.88]). CONCLUSIONS Comorbid stress and/or depressive symptoms are common in individuals with diabetes and together are associated with progressively increased risks for adverse CV outcomes.

EMPOWER: A randomized trial using community health workers to deliver a lifestyle intervention program in African American women with Type 2 diabetes: Design, rationale, and baseline characteristics☆

BACKGROUND African American (AA) women with Type 2 diabetes mellitus (T2DM) in the rural south experience less weight loss and poorer glycemic control in traditional diabetes management programs compared to Caucasians. This paper describes the design, rationale, and baseline characteristics from an innovative community health worker (CHW) delivered intervention program in this population. METHODS/DESIGN This prospective trial randomized rural AA women with uncontrolled T2DM (HbA1c ≥ 7.0) to receive a behaviorally-centered, culturally-tailored lifestyle intervention during 16 contacts from a trained AA CHW or 16 approved diabetes educational mailings. Changes from baseline in glycosylated hemoglobin levels (HbA1c), blood pressure (BP), weight, body mass index (BMI), self-reported dietary and physical activity patterns, and psychosocial measures including diabetes distress, empowerment, depression, self-care, medication adherence, and life satisfaction will be assessed at 6- and 12-months. BASELINE RESULTS Two hundred AA women (mean age = 53.09 ± 10.89 years) with T2DM from impoverished rural communities were enrolled. Baseline data demonstrated profoundly uncontrolled diabetes of long term duration (mean HbA1c = 9.11 ± 1.82; mean BMI = 37.68 ± 8.20; mean BP = 134.51 ± 20.39/84.19 ± 11.68; 10.5 ± 0.7 years). Self-care behavior assessment revealed poor dietary and medication adherence and sedentary lifestyle. Most psychosocial measures ranged within normal limits. CONCLUSION The present sample of AA women from impoverished rural communities exhibited significantly uncontrolled T2DM of long duration with associated obesity and poor lifestyle behaviors. An innovative CHW led lifestyle intervention may lead to more effective strategies for T2DM management in this population.

Herpes Zoster Knowledge, Prevalence, and Vaccination Rate by Race

Objectives: To determine the prevalence of self-reported herpes zoster (HZ) disease and vaccination in a geriatric population and to characterize the deciding factors to receive the HZ vaccine. Methods: This was a cross-sectional survey of patients older than age 60 years at 3 university-based primary care clinics in the southeastern United States. Participants provided information for age, race, sex, education level, history of having “shingles” or knowing someone else who had shingles, past vaccinations, and factors influencing their decision to receive the HZ vaccine. Results: We surveyed 403 patients (49% African American [AA], 47% white). The prevalence of HZ was 12.4% overall and was significantly different among races (8% AA, 17% white; P = .01). Only 29% of patients (16% AA, 42% white; P < .001) were aware that the HZ vaccine was recommended. The HZ vaccination rate was 7.7% (2% AA, 14% white; P < .001). Only 13.7% of all study subjects reported having any communication with their medical providers regarding the HZ vaccine. Physician recommendation and media had the greatest influence on patients who received the vaccine. Of those who had not been vaccinated, 70% had never heard about it and 59% were interested in receiving the vaccine after the survey. Conclusion: There is a large difference in self-reported HZ and vaccination rates among races. The HZ vaccination rate was low overall, but most patients were interested in receiving the vaccine after the survey. More public awareness and education is needed to improve rates of HZ vaccination.

The heart healthy lenoir project-an intervention to reduce disparities in hypertension control: study protocol

BackgroundRacial disparities in blood pressure control are well established; however the impact of low health literacy (LHL) on blood pressure has garnered less attention. Office based interventions that are created with iterative patient, practice and community stakeholder input and are rolled out incrementally, may help address these disparities in hypertension control. This paper describes our study protocol.Methods/designUsing a community based participatory research (CBPR) approach, we designed and implemented a cohort study that includes both a practice level and patient level intervention to enhance the care and support of patients with hypertension in primary care practices in a rural region of eastern North Carolina. The study is divided into a formative phase and an ongoing 2.5 year implementation phase. Our main care enhancement activities include the integration of a community health coach, using home blood pressure monitoring in clinical decision making, standardizing care delivery processes, and working to improve medication adherence. Main outcomes include overall blood pressure change, the differential change in blood pressure by race (African American vs. White) and health literacy level (low vs. higher health literacy).DiscussionUsing a community based participatory approach in primary care practice settings has helped to engage patients and practice staff and providers in the research effort and in making practice changes to support hypertension care. Practices have engaged at varying levels, but progress has been made in implementing and iteratively improving upon the interventions to date.Trial registrationClinicalTrials.gov NCT01425515.