Recurrence analysis methods for the classification of nonlinear systems

Thesis (M.S.) University of Alaska Fairbanks, 2014Recurrence is a common phenomenon in natural systems: A system enters and leaves a state, but after a given period of time, passes near that same state again. Many complex signals, such as weather cycles, heartbeats, or neuron firing patterns, all show recurrence. The recurrence plot (RP) displays all times j where a system returns near a state it has occupied at time i, giving rise to upward-sloping diagonal lines where a system follows a recurrent path, orthogonal lines when the system changes very slowly, or many disconnected points where a system's behavior is unpredictable. Investigation of the RP can then proceed through recurrence quantification analysis (RQA). Three new measures for RQA were developed: diagonality, quantifying diagonal lines, verticality, quantifying vertical lines, and periodicity quantifying the arrangement of recurrence points in periodic structures. These new measures were applied alongside classical recurrence measures to explore trends in random data, identify periodicity and chaotic behavior in the logistic map, estimate the dimensionality of the Lorenz attractor, and discriminate between persistent data signals. In collaboration with biologist Dr. Michael Harris, RQA methods were applied to the discrimination of two neuron types: serotonergic cells are believed to stimulate respiration, while nonserotonergic cells are implicated in respiratory inhibition. Typical discrimination methods compare mean and standard deviation of firing rates to a reference line, which correctly classifies serotonergic cells but incorrectly classifies many nonserotonergic cells. Voltage signals from such cells were converted into inter-spike intervals. Convergence required trials containing over 300 spikes for biological methods, and over 1000 for full investigation using RQA. Whether such cells can be discriminated from baseline firing patterns remains an open question

Who\u27s Distressed? A Comparison of Diabetes-Related Distress by Type of Diabetes and Medication

OBJECTIVE: We hypothesized that diabetes-related distress would vary by type of diabetes and medication regimen [Type 1 diabetes (T1DM), Type 2 diabetes with insulin use (T2DM-i), Type 2 diabetes without insulin use (T2DM)]. Thus, the aim of this study was to identify groups with elevated diabetes-related distress. METHODS: We administered the 17-item Diabetes-related Distress Scale (DDS-17) to 585 patients. We collected demographics, medications, and lab results from patient records. RESULTS: Patients were categorized by type of diabetes and medication: T1DM (n = 149); T2DM-i (n = 333); and T2DM (n = 103). ANOVA revealed significant differences in sample characteristics. ANCOVA were conducted on all four DDS-17 domains [Emotional Burden (EB); Physician-related Distress (PD); Regimen-related Distress (RD); and Interpersonal Distress (ID)]; covariates included in the models were sex, age, duration of diabetes, BMI, and HbA1c. EB was significantly lower in T1DM than T2DM-i, p \u3c 0.05. In addition, RD was significantly lower in T1DM than either T2DM-i, p \u3c 0.05 and T2DM, p \u3c 0.05. CONCLUSIONS: EB and RD are higher for those with type 2 diabetes. Thus, interventions to reduce EB and RD need to be considered for patients with type 2 diabetes. IMPLICATIONS: DDS-17 is useful in identifying diabetes-related distress in patients with diabetes. Efforts need to be made to reduce EB and RD

Getting New Test Results to Patients

New diagnostic results are constantly arriving to outpatient practices. It is imperative to effectively communicate these results and their implications to patients. METHODS: We surveyed 100 patients and our clinic personnel to assess opinions regarding methods of communication in common scenarios. RESULTS: Response rate was 79% from patients and 75% from clinic personnel. Most patients thought letters were an appropriate way to receive normal test results (83%). They also felt medical-technician calls were appropriate for normal results (88%), medication dose changes (75%), or need for additional studies (71%). Respondents considered nurse calls acceptable in most scenarios except for new diagnoses of cancer or need for surgery; the consensus was that physicians should directly communicate to patients in these situations. CONCLUSIONS: Providers should take the time to discuss results with patients that lead to significant interventions, but employ support staff to disseminate information about normal results, medication dose changes, and need for additional diagnostic testing

Diabetes by Air, Land, and Sea: Effect of Deployments on HbA1c and BMI

INTRODUCTION: Service members (SMs) in the United States (U.S.) Armed Forces have diabetes mellitus at a rate of 2-3%. Despite having a chronic medical condition, they have deployed to environments with limited medical support. Given the scarcity of data describing how they fare in these settings, we conducted a retrospective study analyzing the changes in glycated hemoglobin (HbA1c) and body mass index (BMI) before and after deployment. MATERIALS AND METHODS: SMs from the U.S. Army, Air Force, Navy, and Marine Corps with diabetes who deployed overseas were identified through the Military Health System (MHS) Management Analysis and Reporting Tool and the Defense Manpower Data Center. Laboratory and pharmaceutical data were obtained from the MHS Composite Health Care System and the Pharmacy Data Transaction Service, respectively. Paired t-tests were conducted to calculate changes in HbA1c and BMI before and after deployment. RESULTS: SMs with diabetes completed 11,325 deployments of greater than 90 days from 2005 to 2017. Of these, 474 (4.2%) SMs had both HbA1c and BMI measurements within 90 days prior to departure and within 90 days of return. Most (84.2%) required diabetes medications: metformin in 67.3%, sulfonylureas in 19.0%, dipeptidyl peptidase-4 inhibitors in 13.9%, and insulin in 5.5%. Most SMs deployed with an HbA1c \u3c 7.0% (67.1%), with a mean predeployment HbA1c of 6.8%. Twenty percent deployed with an HbA1c between 7.0 and 7.9%, 7.2% deployed with an HbA1c between 8.0 and 8.9%, and 5.7% deployed with an HbA1c of 9.0% or higher. In the overall population and within each military service, there was no significant change in HbA1c before and after deployment. However, those with predeployment HbA1c \u3c 7.0% experienced a rise in HbA1c from 6.2 to 6.5% (P \u3c 0.001), whereas those with predeployment HbA1c values ≥7.0% experienced a decline from 8.0 to 7.5% (P \u3c 0.001). Those who deployed between 91 and 135 days had a decline in HbA1c from 7.1 to 6.7% (P = 0.010), but no significant changes were demonstrated in those with longer deployment durations. BMI declined from 29.6 to 29.3 kg/m2 (P \u3c 0.001), with other significant changes seen among those in the Army, Navy, and deployment durations up to 315 days. CONCLUSIONS: Most SMs had an HbA1c \u3c 7.0%, suggesting that military providers appropriately selected well-managed SMs for deployment. HbA1c did not seem to deteriorate during deployment, but they also did not improve despite a reduction in BMI. Concerning trends included the deployment of some SMs with much higher HbA1c, utilization of medications with adverse safety profiles, and the lack of HbA1c and BMI evaluation proximal to deployment departures and returns. However, for SMs meeting adequate glycemic targets, we demonstrated that HbA1c remained stable, supporting the notion that some SMs may safely deploy with diabetes. Improvement in BMI may compensate for factors promoting hyperglycemia in a deployed setting, such as changes in diet and medication availability. Future research should analyze in a prospective fashion, where a more complete array of diabetes and readiness-related measures to comprehensively evaluate the safety of deploying SMs with diabetes

Effect of Military Deployment on Diabetes Mellitus in Air Force Personnel

Introduction: Military deployments relocate service members to austere locations with limited medical capabilities, raising uncertainties whether members with diabetes can participate safely. Military regulations require a medical clearance for service members with diabetes prior to deployment, but there is a dearth of data that can guide the provider in this decision. To alleviate the lack of evidence in this area, we analyzed the change in glycated hemoglobin (HbA1c) and body mass index (BMI) before and after a deployment among active duty U.S. Air Force personnel who deployed with diabetes. Materials and Methods: A retrospective analysis was conducted using HbA1c and BMI values obtained within 3 mo before and within 3 mo after repatriation from a deployment of at least 90 d between January 1, 2004 through December 31, 2014. The study population consisted of 103 and 195 subjects who had an available pre- and post-deployment HbA1c and BMI values, respectively. Paired t-tests were conducted to determine significant differences in HbA1C and BMI values. Results: The majority (73.8%) of members had a HbA1c7%. BMI declined for the overall population (28.3 kg/m2 vs. 27.7 kg/m2, p \u3c 0.0001) and for most of the subgroups. Conclusion: Air Force service members who deployed with diabetes, including those with a HbA1c \u3e 7%, experienced a statistically significant improvement in HbA1c and BMI upon repatriation. A prospective study design in the future can better reconcile the effect of a military deployment on a more comprehensive array of diabetes parameters

Evaluation of Total Daily Dose and Glycemic Control for Patients Taking U-500 Regular Insulin Admitted to the Hospital

OBJECTIVE: Patients using U-500 regular insulin are severely insulin resistant, requiring high doses of insulin. It has been observed that a patient\u27s insulin requirements may dramatically decrease during hospitalization. This study sought to systematically investigate this phenomenon. METHODS: We performed a retrospective chart review of patients with U-500 insulin outpatient regimens who were admitted to the San Antonio Military Medical Center over a 5-year period. Each patient\u27s outpatient total daily dose (TDD) of insulin was compared to the average inpatient TDD. The outpatient estimated average glucose (eAG) was calculated from the glycated hemoglobin (HbA1c) and compared to the average inpatient glucose. RESULTS: There were 27 patients with a total of 62 separate admissions. The average age was 64.4 years, with a mean body mass index of 38.9 kg/m CONCLUSION: U-500 insulin is prone to errors in the hospital setting, so conversion to U-100 insulin is a preferred option. Despite a significant reduction in insulin TDD, these patients had clinically similar glucose levels. Therefore, patients taking U-500 insulin as an outpatient can be converted to a U-100 basal-bolus regimen with at least a 50% reduction of their outpatient TDD. ABBREVIATIONS: BG = blood glucose eAG = estimated average glucose HbA1c = glycated hemoglobin NPO = nil per os SPSS = Statistical Package for the Social Sciences TDD = total daily dose

Neutral Effect of Exenatide on Serum Testosterone in Men with Type 2 Diabetes Mellitus: A Prospective Cohort

BACKGROUND: Endogenous testosterone increases with weight loss from diet, exercise, and bariatric surgery. However, little is known about testosterone levels after weight loss from medication. OBJECTIVES: Uncover the effects of Glucagon-Like Peptide-1 receptor agonist (GLP-1 RA) therapy on serum testosterone. MATERIAL AND METHODS: Prospective cohort study of men starting GLP-1 RA therapy for type 2 diabetes mellitus. RESULTS: 51 men lost 2.27 kg (p = 0.00162) and their HbA1c values improved by 0.7% (p = 0.000503) after 6 months of GLP-1 RA therapy. There was no significant change in testosterone for the group as a whole. However, in subgroup analyses, there was a significant difference in total testosterone change between men starting with baseline total testosterone/dL (238.5 ± 56.5 ng/dL to 272.2 ± 82.3 ng/dL) compared to higher values (438 ± 98.2 ng/dL to 412 ± 141.2 ng/dL) (p = 0.0172);free testosterone increased if the baseline total testosterone was/dL (55.2 ± 12.8 pg/mL to 57.2 ± 17.6 pg/mL) and decreased if \u3e320 ng/dL (74.7 ± 16.3 pg/mL to 64.2 ± 17.7 pg/mL) (p = 0.00807). Additionally, there were significant differences in testosterone change between men with HbA1c improvements ≥1% (351.6 ± 123.9 ng/dL to 394.4 ± 136.5 ng/dL) compared to men with HbA1c changes CONCLUSION: GLP-1 RA therapy improves weight and HbA1c without adverse effects on testosterone. Those starting with lower testosterone values or attaining greater improvement in HbA1c may see additional benefits

Analysis of Current Thyroid Function Test Ordering Practices

RATIONALE: Current guidelines recommend thyroid stimulating hormone (TSH) alone as the best test to detect and monitor thyroid dysfunction, yet free thyroxine (FT4) and free triiodothyronine (FT3) are commonly ordered when not clinically indicated. Excessive testing can lead to added economic burden in an era of rising healthcare costs, while rarely contributing to the evaluation or management of thyroid disease. OBJECTIVE: To evaluate our institution\u27s practice in ordering thyroid function tests (TFTs) and to identify strategies to reduce inappropriate FT4 and FT3 testing. METHODS: A record of all TFTs obtained in the San Antonio Military Health System during a 3-month period was extracted from the electronic medical record. The TFTs of interest were TSH, FT4, thyroid panel (TSH + FT4), FT3, total thyroxine (T4), and total triiodothyronine (T3). These were categorized based on the presence or absence of hypothyroidism. RESULTS: Between August 1 and October 31, 2016, there were 38 214 individual TFTs ordered via 28 597 total laboratory requests; 11 486 of these requests were in patients with a history of hypothyroidism. The number (percent) of laboratory requests fell into these patterns: TSH alone 14 919 (52.14%), TSH + FT4 7641 (26.72%), FT3 alone 3039 (10.63%), FT4 alone 1219 (4.26%), TSH + FT4 + FT3 783 (2.74%), and others 996 (3.48%); 36.0% of TFTs ordered were free thyroid hormones. Projected out to a year, using Department of Defense laboratory costs, $317 429 worth of TFTs would be ordered, with free thyroid hormone testing accounting for$107 720. CONCLUSION: Inappropriate ordering of free thyroid hormone tests is common. In an era of rising healthcare costs, inappropriate thyroid function testing is an ideal target for efforts to reduce laboratory overutilization, which in our system, could save up to $120 000 per year. Further evaluation is needed to determine strategies that can reduce excessive thyroid hormone testing

Leadership Training in Endocrinology Fellowship? A Survey of Program Directors and Recent Graduates

Context: There is growing recognition that more physician leaders are needed to navigate the next era of medicine. Objective: To determine current opinions about leadership training in endocrinology fellowship programs. Design/Participants: Twenty-seven-question survey addressing various aspects of leadership training to current nationwide fellowship program directors (PDs) and fellowship graduates since 2010. Intervention: In partnership with the Endocrine Society, the electronic survey was advertised primarily via direct e-mail. It was open from March through July 2016. Main Outcome Measures: The survey addressed leadership traits, importance of leadership training, preferred timing, and content of leadership training. Results: Forty-six of 138 PDs (33.3%) and 147 of 1769 graduates (8.3%) completed the survey. Among PDs and graduates, there was strong agreement (\u3e95%) about important leadership characteristics, including job knowledge, character traits, team-builder focus, and professional skills. PDs (64.5%) and graduates (60.8%) favored teaching leadership skills during fellowship, with PDs favoring mentoring/coaching (75.0%), direct observation of staff clinicians (72.5%), and seminars (72.5%). Graduates favored a variety of approaches. Regarding topics to include in a leadership curriculum, PDs responded that communication skills (97.5%), team building (95.0%), professional skills (90.0%), clinic management (87.5%), strategies to impact the delivery of endocrinology care (85.0%), and personality skills (82.5%) were most important. Graduates responded similarly, with \u3e80% agreement for each topic. Finally, most PDs (89%) expressed a desire to incorporate more leadership training into their programs. Conclusions: Our survey suggests a need for leadership training in endocrinology fellowships. More work is needed to determine how best to meet this need

Academic detailing to increase colorectal cancer screening by primary care practices in Appalachian Pennsylvania

<p>Abstract</p> <p>Background</p> <p>In the United States, colorectal cancer (CRC) is the third most frequently diagnosed cancer and second leading cause of cancer death. Screening is a primary method to prevent CRC, yet screening remains low in the U.S. and particularly in Appalachian Pennsylvania, a largely rural area with high rates of poverty, limited health care access, and increased CRC incidence and mortality rates. Receiving a physician recommendation for CRC screening is a primary predictor for patient adherence with screening guidelines. One strategy to disseminate practice-oriented interventions is academic detailing (AD), a method that transfers knowledge or methods to physicians, nurses or office staff through the visit(s) of a trained educator. The objective of this study was to determine acceptability and feasibility of AD among primary care practices in rural Appalachian Pennsylvania to increase CRC screening.</p> <p>Methods</p> <p>A multi-site, practice-based, intervention study with pre- and 6-month post-intervention review of randomly selected medical records, pre- and post-intervention surveys, as well as a post-intervention key informant interview was conducted. The primary outcome was the proportion of patients current with CRC screening recommendations and having received a CRC screening within the past year. Four practices received three separate AD visits to review four different learning modules.</p> <p>Results</p> <p>We reviewed 323 records pre-intervention and 301 post-intervention. The prevalence of being current with screening recommendation was 56% in the pre-intervention, and 60% in the post-intervention (p = 0. 29), while the prevalence of having been screened in the past year increased from 17% to 35% (p < 0.001). Colonoscopies were the most frequently performed screening test. Provider knowledge was improved and AD was reported to be an acceptable intervention for CRC performance improvement by the practices.</p> <p>Conclusions</p> <p>AD appears to be acceptable and feasible for primary care providers in rural Appalachia. A ceiling effect for CRC screening may have been a factor in no change in overall screening rates. While the study was not designed to test the efficacy of AD on CRC screening rates, our evidence suggests that AD is acceptable and may be efficacious in increasing recent CRC screening rates in Appalachian practices which could be tested through a randomized controlled study.</p