Oyer D.S.,Associates in Internal Medicine |
Shepherd M.D.,Endocrinology Consultants |
Coulter F.C.,Coulter Clinic |
Bhargava A.,Iowa Diabetes and Endocrinology Center |
And 3 more authors.
Clinical Therapeutics | Year: 2011
Background: The Initiation of Insulin to reach A1C Target (INITIATEplus) trial studied the effect of self-titrating biphasic insulin aspart 70/30 (BiAsp 30) twice daily during 24 weeks in insulin-naïve patients with type 2 diabetes who were poorly controlled by oral medication, and originally randomized according to frequency of dietary counseling interventions. Objective: The purpose of this study was to compare the efficacy and tolerability of biphasic insulin aspart 70/30 (BIAsp 30, NovoLog Mix 70/30) in INITIATEplus patients 65 versus >65 years old, irrespective of dietary counseling frequency, and to test the hypothesis that self-titrating BIAsp 30 in patients >65 years old could be well-tolerated and effective in this age group. Methods: An exploratory post hoc subanalysis, using standard statistical methods, was performed on patients stratified according to age. Data collected from 3492 patients in the intent-to-treat population who were 65 years old and 716 patients who were >65 years old compared glycosylated hemoglobin (HbA 1c) and plasma glucose changes from baseline. Hypoglycemia rates and adverse event (AE) incidence were compared for the tolerability population of 4007 patients 65 years old and 805 patients >65 years old. Results: Baseline-adjusted HbA 1c changes for patients 65 versus >65 years old were -2.38% versus -2.73% (P < 0.0001), with final HbA 1c achieving 7.55% and 7.06%, respectively. Thirty-nine percent of patients 65 years old achieved HbA 1c % compared with 51% of patients >65 years old. Baseline-adjusted fasting plasma glucose decreases were greater for the >65 year old population (85.2 vs 91.2 mg/dL; P = 0.004; 65 vs >65 years old, respectively). Minor hypoglycemia was reported in 9.7% and 7.7% of patients 5 versus >65 years old, respectively (0.52 vs 0.41 episodes per patient per year [ppy]; P = 0.01). Major hypoglycemia occurred in 1.5% and 3.1% of patients (0.05 vs 0.14 episodes ppy, 65 vs >65 years old, respectively; P < 0.0001). Nocturnal major hypoglycemia was reported for 0.4% and 0.6% of patients (P = 0.0028), whereas nocturnal minor hypoglycemia was reported for 3.8% and 2.6% (P = 0.007) of patients 5 and >65 years old, respectively. AEs were reported for 24% and 28% of patients 65 and >65 years old, respectively, serious AEs were reported for 4% and 9% of patients, respectively, and AE-related withdrawals were reported for 1.3% and 2% of patients, respectively. Conclusions: Self-titrated biphasic insulin aspart 70/30 was found to be well-tolerated and effective in type 2 diabetes patients >65 years old, as well as in patients 65 years old. HbA 1c and fasting plasma glucose decreases were significantly (P < 0.05) higher for patients >65 years old versus patients 65 years old. Tolerability was indicated by major and minor hypoglycemia rates at or below <0.5 episodes ppy in both age groups. Overall rates of AE and serious AEs were higher among patients > 65 years; withdrawals related to AEs were 2% compared with 1.3% in the younger age group. ClinicalTrials.gov identifier: NCT 00101751. © 2011 Elsevier HS Journals, Inc.
The impact of benign gene expression classifier test results on the endocrinologist-patient decision to operate on patients with thyroid nodules with indeterminate fine-needle aspiration cytopathology
Duick D.S.,Endocrinology Associates |
Klopper J.P.,Aurora University |
Diggans J.C.,Veracyte |
Friedman L.,Veracyte |
And 3 more authors.
Thyroid | Year: 2012
Background: Seventy-five percent of thyroid nodules with indeterminate fine-needle aspiration (FNA) cytology are found to be benign postoperatively. A novel genomic test, the Afirma® gene expression classifier (AGEC), has been available for clinical use in the United States, since late 2010. In 2010, two modest-sized validation studies showed that the AGEC could identify a benign gene expression signature in indeterminate cytology thyroid FNA samples with a negative predictive value >95%. The objective of this study was to evaluate how the AGEC impacted the joint decision of the endocrinologist and patient to operate when FNA cytology was indeterminate, but the AGEC reading of the nodule was benign. Methods: In this cross-sectional cohort study, data were contributed retrospectively by 51 endocrinologists at 21 practice sites that had previously obtained ≥3 benign AGEC readings in ≥1 cm nodules with indeterminate FNA cytology readings. Information regarding demographic data, nodule size and location, decision to operate, surgery type (hemithyroidectomy [HT] or total thyroidectomy [TT]), and reason for recommending surgery was retrospectively collected. Results: Compared to a 74% previous historical rate of surgery for cytologically indeterminate nodules, the operative rate fell to 7.6% during the period that AGEC were obtained in the clinical practices, a highly significant reduction in the decision to operate (p<0.001). The rate of surgery on cytologically indeterminate nodules that were benign by the AGEC reading did not differ from the historically reported rate of operation on cytologically benign nodules (p=0.41). The four primary reasons reported by the physicians for operating on nodules with a benign AGEC reading, in descending order: large nodule size (46.4%), symptomatic nodules (25.0%), rapidly growing nodules (10.7%), or a second suspicious or malignant nodule in the same patient (10.7%). These reasons are concordant with those typically given for operation on cytologically benign nodules. Conclusions: In a substantial group of medical practices, obtaining an AGEC test in patients with cytologically indeterminate nodules was associated with a striking reduction in the rate of diagnostic thyroidectomy. Approximately, one surgery was avoided for every two AGEC tests run on thyroid FNAs with indeterminate cytology. © 2012, Mary Ann Liebert, Inc.
PubMed | University of Leipzig, Endocrinology Associates, Haifa University, Arcispedale Santa Maria Nuova and 6 more.
Type: Journal Article | Journal: Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists | Year: 2014
Clinical practice guidelines (CPGs) could have a more consistent and meaningful impact on clinician behavior if they were delivered as electronic algorithms that provide patient-specific advice during patient-physician encounters. We developed a computer-interpretable algorithm for U.S. and European users for the purpose of diagnosis and management of thyroid nodules that is based on the AACE, AME, ETA Medical Guidelines for Clinical Practice for the Diagnosis and Management of Thyroid Nodules, a narrative, evidence-based CPG.We initially employed the guideline-modeling language GuideLine Interchange Format, version 3, known as GLIF3, which emphasizes the organization of a care algorithm into a flowchart. The flowchart specified the sequence of tasks required to evaluate a patient with a thyroid nodule. PROforma, a second guideline-modeling language, was then employed to work with data that are not necessarily obtained in a rigid flowchart sequence. Tallis-a user-friendly web-based enactment tool- was then used as the execution engine (computer program). This tool records and displays tasks that are done and prompts users to perform the next indicated steps. The development process was iteratively performed by clinical experts and knowledge engineers.We developed an interactive web-based electronic algorithm that is based on a narrative CPG. This algorithm can be used in a variety of regions, countries, and resource-specific settings.Electronic guidelines provide patient-specific decision support that could standardize care and potentially improve the quality of care. The demonstrator electronic thyroid nodule guideline that we describe in this report is available at http://demos.deontics.com/trace-review-app (username: reviewer; password: tnodule1). The demonstrator must be more extensively trialed before it is recommended for routine use.
Djenic B.,Maricopa Medical Center |
Duick D.,Endocrinology Associates |
Newell J.O.,Scottsdale Pathology Consultants |
Demeure M.J.,Translational Genomics Research Institute
International Journal of Surgery Case Reports | Year: 2015
Introduction Papillary (PTC) and follicular (FTC) thyroid carcinomas, together known as differentiated thyroid carcinomas (DTC), are among the most curable of cancers. Sites of metastases from FTC are usually osseous and those from PTC are in regional nodal basins and the lungs. Visceral metastases are rare and when they do occur, they tend do so in multiple sites. We present the case of a patient with a follicular variant of PTC and a solitary metastasis to the liver then review the relevant literature.Presentation of case An otherwise healthy 68-year-old woman was diagnosed with follicular variant papillary thyroid cancer in 2003 and subsequently underwent thyroidectomy. The patient's endocrinologist conducted surveillance of her thyroid cancer. In 2012, due to rise in thyroglobulin, a whole body radioiodine scan was obtained which revealed an iodine-avid left liver lobe mass. Three cycles of radioiodine ablation therapy were unsuccessful and eventually the patient was referred for surgical resection. Metastatic evaluation including a PET scan was negative with the exception of an isolated enhancing 4 cm mass in segment 4B of the liver. Anatomic segmental resection of liver was performed without complications. Intraoperative ultrasonography was used to guide resection of the liver mass. Pathology reports confirmed metastatic follicular variant of PTC. Surgical margins were free of tumor. Patient was discharged home and is doing well one year after surgery. The latest thyroglobulin level was undetectable.Discussion Post-operative surveillance by PCP, endocrinologist or surgeon for patients with thyroid carcinoma should be performed routinely. If identified, a solitary liver metastasis from primary thyroid carcinoma should be considered for surgical resection. Due to sparse data available in literature, collecting more data to establish algorithms for treatment of such rare metastatic cancers may be able to aid physicians to achieve better outcomes.Conclusion Rare distant sites of metastases from DTC include eyes, pharynx, skin, muscle, ovaries, adrenal glands, kidneys, esophagus, pancreas and liver. Isolated, resectable liver metastases from PTC are exceedingly rare. Literature review revealed only 10 reported cases of liver metastases from DTC. As in our patient, solitary liver metastasis from PTC should be considered for surgical resection which offers the best chance for prolonged survival. © 2014 Published by Elsevier Ltd.
Johnson J.L.,Endocrinology Associates |
Duick D.S.,Endocrinology Associates |
Chui M.A.,University of Wisconsin - Madison |
Aldasouqi S.A.,Saint Francis Medical Center College of Nursing
Endocrine Practice | Year: 2010
Objective: To determine whether patients with prediabetes can be accurately and easily identified in clinical settings using a predictive clinical and laboratory model. Methods: This retrospective study examined demographic and laboratory data from patients who had undergone 2-hour glucose testing for suspected prediabetes or diabetes between 2000 and 2004. Patients who met the diagnostic criteria for diabetes mellitus were excluded. Prediabetes was defined as a fasting glucose concentration ≥100 mg/dL and ≤125 mg/dL or a 2-hour postprandial glucose concentration ≥140 mg/dL and <200 mg/dL. Multivariate logistic regression was conducted to identify calculated or measured clinical and laboratory attributes that predict the presence of prediabetes, including fasting insulin quartiles, homeostasis model assessment of insulin resistance (HOMA-IR), and quantitative insulin sensitivity check index. Results: Of 965 patients, 287 (29.7%) had prediabetes. The study population primarily consisted of white, obese, female patients. A multivariate model revealed that compared with the referent lowest quartile of fasting insulin (μ = 4.9 [±SD] ± 1.2 μIU/mL), subsequent insulin quartiles increased the likelihood of identifying prediabetes (quartile 2: μ = 8.0 ± 0.8 μIU/mL, odds ratio [OR] = 2.076, confidence interval [CI] = 1.241-3.273; quartile 3: μ = 12.2 ± 1.7 μIU/mL, OR = 3.151, CI = 1.981-5.015; quartile 4: μ = 25.9 ± 12.4 μIU/mL, OR = 5.035, CI = 3.122-8.122). Older age and increased diastolic blood pressure also contributed modestly to this model. Further analysis using the area under the curve revealed that at a fasting insulin level >9.0 μIU/mL, prediabetes would be correctly identified in 80% of affected patients. A second model revealed that increased HOMA-IR index (OR = 1.303, CI = 1.205-1.410) and older age (OR = 1.037, CI = 1.024-1.05) predicted prediabetes. Conclusions: The most robust model, which used fasting insulin levels, may provide the most utility as a clinical tool because the highest quartiles suggest significantly greater likelihood of identifying prediabetes. © 2010 AACE.
Weissman P.N.,Endocrinology Associates |
Carr M.C.,Glaxosmithkline |
Ye J.,Glaxosmithkline |
Cirkel D.T.,Glaxosmithkline |
And 3 more authors.
Diabetologia | Year: 2014
Aims/hypothesis The aim of this study was to compare the efficacy and safety of once-weekly albiglutide with once-daily insulin glargine (A21Gly,B31Arg,B32Arg human insulin) in patients with type 2 diabetes inadequately controlled on metformin with or without sulfonylurea. Methods This was a randomised, open-label, multicentre (n=222), parallel-group, non-inferiority out-patient clinical trial, with 779 patients enrolled in the study. The study was conducted in 222 centres located in four countries. Patients aged ≥18 years with type 2 diabetes treated with metformin (±sulfonylurea) for at least 3 months with a baseline HbA1c 7.0-10.0% (53.0-85.8 mmol/mol) were randomly assigned (2:1) via a computer-generated randomisation sequence with a voice response system to receive albiglutide (30 mg once a week, n=504) or insulin glargine (10 U once a day, n=241) added to current therapy. Participants and investigators were not masked to treatment assignment. Doses of each medication were adjusted on the basis of the glycaemic response. The primary endpoint was change from baseline in HbA1c at week 52. Results In the albiglutide group, HbA1c declined from 8.28± 0.90% (67.0±9.8 mmol/mol) (mean±SD) at baseline to 7.62± 1.12% (59.8±12.2 mmol/mol) at week 52. A similar reduction occurred in the insulin glargine group (8.36±0.95% to 7.55± 1.04% [67.9±10.4 to 59.0±11.4 mmol/mol]). The modeladjusted treatment difference of 0.11% (95% CI −0.04%, 0.27%) (1.2 mmol/mol [95% CI −0.4, 3.0 mmol/mol]) indicated non-inferiority of albiglutide to insulin glargine based on the pre-specified non-inferiority margin of 0.3% (3.3 mmol/mol, p=0.0086). Bodyweight increased in the insulin glargine group and decreased in the albiglutide group, with a mean treatment difference of −2.61 kg (95% CI −3.20, −2.02; p<0.0001). Documented symptomatic hypoglycaemia occurred in a higher proportion of patients in the insulin glargine group than in the albiglutide group (27.4% vs 17.5%, p=0.0377). Conclusions/interpretation Albiglutide was non-inferior to insulin glargine at reducing HbA1c at week 52, with modest weight loss and less hypoglycaemia. Both drugs were well tolerated. Albiglutide may be considered an alternative to insulin glargine in this patient population. Trial registration: ClinicalTrials.gov NCT00838916 (completed) Funding: This study was planned and conducted by GlaxoSmithKline. © 2014, Springer-Verlag Berlin Heidelberg.
Dutt-Ballerstadt R.,Biotex, Inc. |
Evans C.,Biotex, Inc. |
Pillai A.P.,Biotex, Inc. |
Orzeck E.,Endocrinology Associates |
And 3 more authors.
Journal of Diabetes Science and Technology | Year: 2012
Objective: We report results of a pilot clinical study of a subcutaneous fluorescence afinity sensor (FAS) for continuous glucose monitoring conducted in people with type 1 and type 2 diabetes. The device was assessed based on performance, safety, and comfort level under acute conditions (4 h). Research Design and Methods: A second-generation FAS (BioTex Inc., Houston, TX) was subcutaneously implanted in the abdomens of 12 people with diabetes, and its acute performance to excursions in blood glucose was monitored over 4 h. After 30-60 min the subjects, who all had fasting blood glucose levels of less than 200 mg/dl, received a glucose bolus of 75 g/liter dextrose by oral administration. Capillary blood glucose samples were obtained from the finger tip. The FAS data were retrospectively evaluated by linear least squares regression analysis and by the Clarke error grid method. Comfort levels during insertion, operation, and sensor removal were scored by the subjects using an analog pain scale. Results: After retrospective calibration of 17 sensors implanted in 12 subjects, error grid analysis showed 97% of the paired values in zones A and B and 1.5% in zones C and D, respectively. The mean absolute relative error between sensor signal and capillary blood glucose was 13% [±15% standard deviation (SD), 100-350 mg/dl] with an average correlation coeficient of 0.84 (±0.24 SD). The actual average "warm-up" time for the FAS readings, at which highest correlation with glucose readings was determined, was 65 (±32 SD) min. Mean time lag was 4 (±5 SD) min during the initial operational hours. Pain levels during insertion and operation were modest. Conclusions: The in vivo performance of the FAS demonstrates feasibility of the fluorescence afinity technology to determine blood glucose excursions accurately and safely under acute dynamic conditions in humans with type 1 and type 2 diabetes. Specific engineering challenges to sensor and instrumentation robustness remain. Further studies will be required to validate its promising performance over longer implantation duration (5-7 days) in people with diabetes. © Diabetes Technology Society.
Duick D.S.,Endocrinology Associates
Endocrine Practice | Year: 2012
Objective: To provide information on molecular biomarkers that can help assess cytologically indeterminate thyroid nodules.Methods: Published studies on immunohistologic, somatic mutation, gene expression classifier, microRNA, and thyrotropin receptor messenger RNA biomarkers are reviewed, and commercially available molecular test panels are described.Results: Thyroid nodules are common, and clinical guidelines delineate an algorithmic approach including serum thyroid-stimulating hormone measurement, diagnostic ultrasound examination, and, when appropriate, fine-needle aspiration (FNA) biopsy for determination of a benign versus malignant status. In clinical practice, approximately 20% of FNA-derived cytology reports are classified as "indeterminate" or follicular nodules that do not fulfill either benign or malignant criteria. In this setting, the actual risk for malignancy of a cytologically indeterminate nodule ranges from approximately 15% to 34%. Research describing molecular biomarkers from thyroid cancer tissue has been applied to FNA-derived thyroid nodule material. There is also a serum molecular marker that has been reported with goals similar to those for the FNA-derived molecular markers: to enhance the preoperative diagnosis of thyroid cancer and reduce the large number of patients who have a diagnostic surgical procedure for benign thyroid nodules.Conclusion: Progress toward the foregoing goals has been made and continues to evolve with the recent appearance of molecular biomarker tests that can be selectively applied for further assessment of cytologically indeterminate thyroid nodules. Copyright © 2012 AACE.
PubMed | Endocrinology Associates
Type: Clinical Trial | Journal: Current medical research and opinion | Year: 2012
To determine if self-titration using biphasic insulin aspart 70/30 (BIAsp 30) had a different impact on efficacy and safety across different racial/ethnic subgroups.This was an exploratory, post hoc analysis by race (White vs. Black/African-American) and ethnicity (Hispanic/Latino vs. non-Hispanic/Latino) of data from the INITIATEplus trial. Participants were treated twice-daily with BIAsp 30 over 24 weeks.NCT00101751.Efficacy endpoints included reductions in mean glycated hemoglobin (A1C) and fasting plasma glucose (FPG). Safety endpoints included hypoglycemia rates (events/patient-year) and adverse events. Body weight changes were also measured.Glycemic control improved by a similar extent for all demographic groups. Observed mean decreases in A1C ranged from 2.4% to 2.6% after 24 weeks treatment. Baseline-adjusted mean A1C decreases for White vs. Black/African-American subjects were 2.56% and 2.13% (p<0.0001), and for Hispanic/Latino vs. non-Hispanic/Latino subjects were 2.45% and 2.42% (p=0.677), respectively. Final FPG values were similar among all groups (141-146mg/dL [7.83-8.10mmol/L]), and baseline-adjusted FPG decreases were not significantly different (p>0.025) between groups. Hypoglycemia was low for White, Black/African-American, Hispanic/Latino, and non-Hispanic/Latino subjects (0.08, 0.04, 0.03, and 0.07 major events/patient-year, with 0.60, 0.30, 0.37, and 0.52 minor events/patient-year, respectively). Body weight increases were 3.17 and 3.06kg (White vs. African-American) and 2.69 and 3.19kg (Hispanic/Latino vs. non-Hispanic/Latino). Final weight-adjusted total daily insulin doses were 0.60 U/kg for Black/African-American subjects vs. 0.78 U/kg for White subjects (p<0.0001), and 0.71 U/kg for Hispanic/Latino subjects vs. 0.74 U/kg for non-Hispanic/Latino subjects (p=0.42).The trial was not designed or powered for comparisons across racial or ethnic groups, subjects were not stratified for pre-baseline medication regimens between each race and ethnic group, and unequal subject numbers and baseline A1C disparities existed between the pairs of groups being compared.Diabetes self-management with BIAsp 30 using an easily followed self-titration algorithm produced low hypoglycemia rates. All subgroups achieved A1C reductions >2.1% and FPG declines >82mg/dL that were similar across groups, demonstrating that self-titration of BIAsp 30 can successfully be pursued in a primary care setting by patients who had previously failed to meet ADA A1C targets under oral antidiabetes therapy, with race or ethnicity not an obstacle to achieving better glycemic control.
PubMed | Endocrinology Associates
Type: Journal Article | Journal: Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists | Year: 2010
To determine whether patients with prediabetes can be accurately and easily identified in clinical settings using a predictive clinical and laboratory model.This retrospective study examined demographic and laboratory data from patients who had undergone 2-hour glucose testing for suspected prediabetes or diabetes between 2000 and 2004. Patients who met the diagnostic criteria for diabetes mellitus were excluded. Prediabetes was defined as a fasting glucose concentration > or = 100 mg/dL and < or = 125 mg/dL or a 2-hour postprandial glucose concentration > or = 140 mg/dL and < 200 mg/dL. Multivariate logistic regression was conducted to identify calculated or measured clinical and laboratory attributes that predict the presence of prediabetes, including fasting insulin quartiles, homeostasis model assessment of insulin resistance (HOMA-IR), and quantitative insulin sensitivity check index.Of 965 patients, 287 (29.7%) had prediabetes. The study population primarily consisted of white, obese, female patients. A multivariate model revealed that compared with the referent lowest quartile of fasting insulin (mu = 4.9 [+/-SD] +/-1.2 microIU/mL), subsequent insulin quartiles increased the likelihood of identifying prediabetes (quartile 2: mu = 8.0 +/-0.8 microIU/mL, odds ratio [OR] = 2.076, confidence interval [CI] = 1.241-3.273; quartile 3: mu = 12.2 +/-1.7 microIU/mL, OR = 3.151, CI = 1.981-5.015; quartile 4: mu = 25.9 +/-12.4 microIU/mL, OR = 5.035, CI = 3.122-8.122). Older age and increased diastolic blood pressure also contributed modestly to this model. Further analysis using the area under the curve revealed that at a fasting insulin level > 9.0 microIU/mL, prediabetes would be correctly identified in 80% of affected patients. A second model revealed that increased HOMA-IR index (OR = 1.303, CI = 1.205-1.410) and older age (OR = 1.037, CI = 1.024-1.05) predicted prediabetes.The most robust model, which used fasting insulin levels, may provide the most utility as a clinical tool because the highest quartiles suggest significantly greater likelihood of identifying prediabetes.