Intensive Versus Standard Treatment of Hyperglycemia in Acute Ischemic Stroke Patient: A Randomized Clinical Trial Subgroups Analysis.

BACKGROUND: Benefit from blood glucose (BG) control during acute ischemic stroke may depend on glycemic parameters. We evaluated for associations between the SHINE (Stroke Hyperglycemia Insulin Network Effort) randomized treatment group and the SHINE predefined 90-day functional outcome, within-patient subgroups defined by various glycemic parameters. METHODS: The SHINE Trial randomized 1151 patients within 12 hours with acute ischemic stroke and hyperglycemia to standard (target BG 80-179 mg/dL) or intensive (target BG 80-130 mg/dL) BG control for 72 hours. We predefined 6 glycemic parameters: acute BG level, absence versus presence of diagnosed and undiagnosed diabetes, hemoglobin A1c, glycemic gap (acute BG-average daily hemoglobin A1c based BG), stress hyperglycemia ratio (acute BG/average daily hemoglobin A1c based BG), and BG variability (SD). Favorable functional outcome was defined by the SHINE Trial and based on the modified Rankin Scale score at 90 days, adjusted for stroke severity. We computed relative risks adjusted for baseline stroke severity and thrombolysis use. RESULTS: Likelihood for favorable outcome was lowest among patients with undiagnosed diabetes compared to patients with true nondiabetes (adjusted relative risk, 0.42 [99% CI, 0.19-0.94]). We did not find any relationship between the favorable outcome rate and baseline BG or any of the glycemic parameters. No differences between SHINE treatment groups were identified among any of these patient subgroups. CONCLUSIONS: In this exploratory subgroup analysis, intensive versus standard insulin treatment of hyperglycemia in acute ischemic stroke patient subgroups, did not influence the 90-day functional outcomes, nor did we identify associations between these glycemic parameters and 90-day functional outcomes.

Validation of American Thyroid Association Ultrasound Risk Assessment of Thyroid Nodules Selected for Ultrasound Fine-Needle Aspiration.

OBJECTIVE: The aim of this study was to validate the American Thyroid Association (ATA) sonographic risk assessment of thyroid nodules. METHODS: The ATA sonographic risk assessment was prospectively applied to 206 thyroid nodules selected for ultrasound-guided fine-needle aspiration (US-FNA), and analyzed with The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC), as well as surgical pathology for the subset undergoing surgical excision. RESULTS: The analysis included 206 thyroid nodules averaging 2.4 cm (range 1-7 cm; standard error of the mean 0.07). Using the ATA US pattern risk assessment, nodules were classified as high (4%), intermediate (31%), low (38%), and very low (26%) risk of malignancy. Nodule size was inversely correlated with sonographic risk assessment, as lower risk nodules were larger on average (p < 0.0001). Malignancy rates determined by cytology/surgical pathology were high 100%, intermediate 11%, low 8%, and very low 2%, which were closely aligned with ATA malignancy risk estimates (high 70-90%, intermediate 10-20%, low 5-10%, and very low 3%). ATA US pattern risk assessment also appropriately predicted the proportion of nodules classified as malignant or suspicious for malignancy through TBSRTC classification-high (77%), intermediate (6%), low (1%), and very low 0%-as well as benign TBSRTC classification-high (0%), intermediate (47%), low (61%), and very low (70%) (p < 0.0001). Malignancy rates of surgically excised, cytologically indeterminate nodules followed ATA sonographic risk stratification (high 100%, intermediate 21%, low 17%, and very low 12%; p = 0.003). CONCLUSION: This prospective study supports the new ATA sonographic pattern risk assessment for selection of thyroid nodules for US-FNA based upon TBSRTC and surgical pathology results. In the setting of indeterminate cytopathology, nodules categorized as atypia of undetermined significance/follicular lesion of undetermined significance with ATA high-risk sonographic patterns have a high likelihood of being malignant.

Thyroid Ultrasound-Guided Fine-Needle Aspiration Cytology Results: Observed Increase in Indeterminate Rate over the Past Decade.

Objectives To evaluate changes in distribution of reported thyroid nodule fine-needle aspiration (FNA) cytopathology results since implementation of the Bethesda classification and revised 2015 American Thyroid Association (ATA) guidelines for selecting nodules for biopsy. Study Design Retrospective review. Setting Tertiary academic medical center. Subjects and Methods Evaluation of ultrasound (US)-guided thyroid FNA by a single surgeon using 2015 ATA nodule selection criteria and Bethesda reporting on 211 thyroid nodules in a 1-year period (2015). Comparison is made to an earlier sample wherein any nodule >1 cm underwent US FNA with cytology reported prior to Bethesda consensus (2006). Results The current cohort involved mostly women (79%); nodules ranged from 1 to 7 cm (mean ± SEM, 2.4 ± 0.07 cm). Mean ± SEM age was 53.5 ± 1.1 years. Bethesda reporting yielded 6% nondiagnostic, 57% benign, 3% malignant, and 34% indeterminate (27% atypia of undetermined significance [AUS]/follicular lesion of undetermined significance [FLUS], 4% follicular neoplasm [FN]/Hürthle neoplasm [HN], and 2% suspicious for malignancy [SFM]). The malignancy rate in indeterminate nodules was 26% (18% AUS/FLUS, 33% FN/HN, and 80% SFM). Age, sex, or nodule size did not correlate with indeterminate cytology. The comparator sample of 447 nodules had significantly different distribution, with 7% nondiagnostic, 80% benign, 5% malignant, and 8% indeterminate ( P < .00001). Conclusion We observed a significantly increased proportion of indeterminate cytology and corresponding decrease in benign nodules compared with an earlier sample, predominately from an increase in AUS/FLUS. Multiple factors are likely involved, including selection of sonographically suspicious nodules for biopsy based upon 2015 ATA guidelines coupled with cytopathological interpretation by a new generation of cytopathologists trained in the era of Bethesda reporting; further study is required to make a definitive conclusion.

Diabetes Transition Care From an Inpatient to Outpatient Setting in a Veteran Population: Quality Improvement Pilot Study.

PURPOSE: The purpose of the study was to evaluate a diabetes transition care program in a population of veterans with diabetes by calculating 30-day readmission rates and assessing glycemic control. METHODS: Hospitalized patients with poorly controlled diabetes were identified to participate in the diabetes transition care program. The program included follow-up through a postdischarge telephone call by the diabetes educator, with an opportunity for a face-to-face clinic visit. A retrospective before-and-after study design was used. Analysis included calculating the readmission rate and the pre- and postintervention A1C rates to evaluate the intervention. RESULTS: Of the 40 participants, 100% completed the intervention. All 40 participants received a postdischarge telephone call as follow-up, with 20% presenting for a face-to-face visit. The 30-day readmission rate for the cohort was 10%, in comparison to 14.3% for patients who did not receive the intervention but were otherwise comparable. For those who had repeat A1C measurements conducted 2 to 8 months after time of enrollment in the program (n = 33), average A1C declined -2.2%, from 11.3% (100 mmol/mol) to 9.1% (76 mmol/mol). CONCLUSIONS: Diabetes-specific transition of care for those with complex psychiatric, medical, and social needs was feasible, with good outcomes in hospital readmission rates and glycemic control, when executed by an adult nurse practitioner who was the inpatient diabetes educator.

Elective central node dissection: Comparison of open to minimally invasive video-assisted approach.

OBJECTIVES/HYPOTHESIS: Compare outcomes of concomitant primary thyroidectomy with elective central neck dissection (CND) by the standard open versus minimally invasive video-assisted (MIVA) approach. STUDY DESIGN: Case series chart review, single institution, tertiary referral center. METHODS: Current Procedural Terminology code 60252 was used to identify patients undergoing CND from February 2005 through June 2012. Therapeutic CND and revision cases were excluded. The MIVA approach was performed in patients with low-risk thyroid carcinoma (cT1 or 2, cN0). Primary outcomes included nodal yield and complications, and secondary outcomes included recurrence. RESULTS: Of 87 eligible patients, 38 were open and 49 were MIVA. The MIVA group was more likely female (88% vs. 68%, P = .03), but groups were similar in age (46.0 vs. 48.6 mean years, P = .37) and percentage of unilateral dissection (69.4% vs. 71.0%, P = .86). The MIVA group was more often pT1 or 2 (86.9% vs. 76.4%, P = .02). Pathological node positivity was 40% overall and not significantly different between groups (43.5% vs. 35.3%, P = .46). Nodal yield was similar between groups (6.4 vs. 6.8, P = .73). Transient recurrent laryngeal nerve paralysis rates were similar (4.1% vs. 2.6%, P = .71). Transient hypoparathyroidism (postanesthesia care unit parathyroid hormone ≤15 pg/mL) was lower in the MIVA group but not statistically significant (29.2% vs. 45.2%, P = .15). No patients experienced permanent hypoparathyroidism or developed clinically detectable structural recurrence. Rates of biochemical response were similar (any thyroglobulin >1 ng/dL) (13.8% vs. 8.0%, P = .86). CONCLUSIONS: Concomitant MIVA thyroidectomy with elective CND appears to be a safe and effective alternative to the open approach for low-risk thyroid carcinoma with similar nodal yield, complications, and recurrence. LEVEL OF EVIDENCE: 4 Laryngoscope, 126:1715-1718, 2016.

Best practices for centers of excellence in addressing periprosthetic joint infection.

Periprosthetic joint infection is a rare and devastating complication. Management of this complication often requires a multidisciplinary approach similar to that used for the care of patients with cancer. Several studies have reported better outcomes following total joint arthroplasties performed at specialized hospitals than those performed at general hospitals. Specialized institutions use care pathways that aid the multidisciplinary team in decision making. During the recent Musculoskeletal Infection symposium, specific issues were discussed with regard to the treatment of periprosthetic joint infection, including medical optimization, systematic approaches to infection management, and the importance of establishing registries to aid in the creation of Centers of Excellence. A Center of Excellence in periprosthetic infection could provide better overall outcomes with lower financial, physical, and emotional costs to patients.

A pilot study: retention of adults experiencing homelessness and feasibility of a CDSM diabetes program.

INTRODUCTION: The study purpose was to evaluate the feasibility of a chronic disease self management/case management intervention for adults experiencing homelessness and diabetes and the ability to retain subjects. METHODS: Participants with type 2 diabetes were recruited at a homeless clinic and a subset received the intervention. Analysis included calculating a retention rate and evaluating the intervention implementation process. RESULTS: Of the nine participants, five were retained for 12 weeks and two of three participants completed the full intervention. CONCLUSIONS: Study retention is feasible for adults experiencing homelessness. Further intervention refinement is needed to address relevancy of content and time constraints.

Pathways to quality inpatient management of hyperglycemia and diabetes: a call to action.

Currently patients with diabetes comprise up to 25-30% of the census of adult wards and critical care units in our hospitals. Although evidence suggests that avoidance of hyperglycemia (>180 mg/dL) and hypoglycemia (<70 mg/dL) is beneficial for positive outcomes in the hospitalized patient, much of this evidence remains controversial and at times somewhat contradictory. We have recently formed a consortium for Planning Research in Inpatient Diabetes (PRIDE) with the goal of promoting clinical research in the area of management of hyperglycemia and diabetes in the hospital. In this article, we outline eight aspects of inpatient glucose management in which randomized clinical trials are needed. We refer to four as system-based issues and four as patient-based issues. We urge further progress in the science of inpatient diabetes management. We hope this call to action is supported by the American Diabetes Association, The Endocrine Society, the American Association of Clinical Endocrinologists, the American Heart Association, the European Association for the Study of Diabetes, the International Diabetes Federation, and the Society of Hospital Medicine. Appropriate federal research funding in this area will help ensure high-quality investigations, the results of which will advance the field. Future clinical trials will allow practitioners to develop optimal approaches for the management of hyperglycemia in the hospitalized patient and lessen the economic and human burden of poor glycemic control and its associated complications and comorbidities in the inpatient setting.

The role of hyperglycemia in acute illness: supporting evidence and its limitations.

Hyperglycemia is common in acutely ill hospitalized patients and has been linked to poor outcomes, independent of pre-existing diabetes. Correction of hyperglycemia has been shown to decrease morbidity and mortality; however, establishing evidence-based guidelines has been challenging because insulin intervention studies have varied in the questions they have addressed, glucose levels studied, feeding regimen, and quality of methodology. This article reviews the findings and limitations of recent intervention studies that have addressed treatment of inpatient hyperglycemia with intravenous insulin infusion therapy. Discussion of underlying causes of hospital-related hyperglycemia and mechanisms explaining the deleterious effects of hyperglycemia and improved outcomes with insulin intervention are described. Current guidelines from various professional organizations recommend treatment of inpatient hyperglycemia, although exact glycemic targets and identification of which patient subsets will receive greatest benefit from glucose lowering remain an area of ongoing research.

One institution's experience in implementing protocols for glycemic management.

The objective for monitoring blood glucose is to determine the need for intervention. This article describes an institution's comprehensive program of protocols and education initiated to manage inpatient hyperglycemia.

Hyperglycemia-related mortality in critically ill patients varies with admission diagnosis.

OBJECTIVES: Hyperglycemia during critical illness is common and is associated with increased mortality. Intensive insulin therapy has improved outcomes in some, but not all, intervention trials. It is unclear whether the benefits of treatment differ among specific patient populations. The purpose of the study was to determine the association between hyperglycemia and risk- adjusted mortality in critically ill patients and in separate groups stratified by admission diagnosis. A secondary purpose was to determine whether mortality risk from hyperglycemia varies with intensive care unit type, length of stay, or diagnosed diabetes. DESIGN: Retrospective cohort study. SETTING: One hundred seventy-three U.S. medical, surgical, and cardiac intensive care units. PATIENTS: Two hundred fifty-nine thousand and forty admissions from October 2002 to September 2005; unadjusted mortality rate, 11.2%. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A two-level logistic regression model determined the relationship between glycemia and mortality. Age, diagnosis, comorbidities, and laboratory variables were used to calculate a predicted mortality rate, which was then analyzed with mean glucose to determine the association of hyperglycemia with hospital mortality. Hyperglycemia was associated with increased mortality independent of illness severity. Compared with normoglycemic individuals (70-110 mg/dL), adjusted odds of mortality (odds ratio, [95% confidence interval]) for mean glucose 111-145, 146-199, 200-300, and >300 mg/dL was 1.31 (1.26-1.36), 1.82 (1.74-1.90), 2.13 (2.03-2.25), and 2.85 (2.58-3.14), respectively. Furthermore, the adjusted odds of mortality related to hyperglycemia varied with admission diagnosis, demonstrating a clear association in some patients (acute myocardial infarction, arrhythmia, unstable angina, pulmonary embolism) and little or no association in others. Hyperglycemia was associated with increased mortality independent of intensive care unit type, length of stay, and diabetes. CONCLUSIONS: The association between hyperglycemia and mortality implicates hyperglycemia as a potentially harmful and correctable abnormality in critically ill patients. The finding that hyperglycemia-related risk varied with admission diagnosis suggests differences in the interaction between specific medical conditions and injury from hyperglycemia. The design and interpretation of future trials should consider the primary disease states of patients and the balance of medical conditions in the intensive care unit studied.

Molecular testing for mutations in improving the fine-needle aspiration diagnosis of thyroid nodules.

CONTEXT: Thyroid nodules are common in adults, but only a small fraction of them are malignant. Fine-needle aspiration (FNA) with cytological evaluation is the most reliable tool for cancer diagnosis in thyroid nodules. However, 10-40% of nodules are diagnosed as indeterminate by cytology, making it difficult to optimally manage these patients. OBJECTIVE: The aim of this study was to establish the feasibility and role of testing for tumor-specific mutations in improving the FNA diagnosis of thyroid nodules. DESIGN: The prospective study included 470 FNA samples of thyroid nodules from 328 patients. At the time of aspiration, a small portion of the material was collected and tested for BRAF, RAS, RET/PTC, and PAX8/PPARgamma mutations. The mutational status was correlated with cytology and either surgical pathology diagnosis or follow-up (mean, 34 months). RESULTS: A sufficient amount of nucleic acids were isolated in 98% of samples. Thirty-two mutations were found, including 18 BRAF, eight RAS, five RET/PTC, and one PAX8/PPARgamma. The presence of any mutation was a strong indicator of cancer because 31 (97%) of mutation-positive nodules had a malignant diagnosis after surgery. A combination of cytology and molecular testing showed significant improvement in the diagnostic accuracy and allowed better prediction of malignancy in the nodules with indeterminate cytology. CONCLUSIONS: These results indicate that molecular testing of thyroid nodules for a panel of mutations can be effectively performed in a clinical setting. It enhances the accuracy of FNA cytology and is of particular value for thyroid nodules with indeterminate cytology.

Pharmacodynamic effect of iopanoic acid on free T(3) and T(4) levels in amiodarone-induced thyrotoxicosis.

We describe the effects of iopanoic acid on daily levels of free triiodothyronine (FT(3)) and free thyroxine (FT(4)) in a patient with progressive type II amiodarone-induced thyrotoxicosis (AIT) who was undergoing thyroidectomy. The patient was a 59-year-old man who was undergoing amiodarone therapy while awaiting cardiac transplantation; the use of beta blockers and corticosteroids to control the AIT was contraindicated in this patient. Prior to thyroidectomy, the patient was started on iopanoic acid at 1.0 g twice a day; in response to gastrointestinal side effects, the dosage was subsequently reduced to 0.5 g twice a day. The patient responded to iopanoic acid with a rapid decrease in his FT(3) level and slight increase in his FT(4) level. This control of thyrotoxicosis allowed for an uneventful thyroidectomy, which was later followed by successful cardiac transplantation. Based on our findings in this single case, we believe that iopanoic can be used to rapidly lower FT(3) levels and to treat symptoms of thyrotoxicosis in a preoperative setting. We also discuss the different pharmacodynamic effects that iopanoic acid has on FT(3) and FT(4) levels.

Impact of clinical reminder redesign on learnability, efficiency, usability, and workload for ambulatory clinic nurses.

OBJECTIVE: Computerized clinical reminders (CRs) were designed to reduce clinicians' reliance on their memory and to present evidence-based guidelines at point of care. However, the literature indicates that CR adoption and effectiveness has been variable. We examined the impact of four design modifications to CR software on learnability, efficiency, usability, and workload for intake nursing personnel in an outpatient clinic setting. These modifications were included in a redesign primarily to address barriers to effective CR use identified during a previous field study. DESIGN: In a simulation experiment, 16 nurses used prototypes of the current and redesigned system in a within-subject comparison for five simulated patient encounters. Prior to the experimental session, participants completed an exploration session, where "learnability" of the current and redesigned systems was assessed. MEASUREMENTS: Time, performance, and survey data were analyzed in conjunction with semi-structured debrief interview data. RESULTS: The redesign was found to significantly increase learnability for first-time users as measured by time to complete the first CR, efficiency as measured by task completion time for two of five patient scenarios, usability as determined by all three groupings of questions taken from a commonly used survey instrument, and two of six workload subscales of the NASA Task Load Index (TLX) survey: mental workload and frustration. CONCLUSION: Modest design modifications to existing CR software positively impacted variables that likely would increase the willingness for first-time nursing personnel to adopt and consistently use CRs.

Causes and consequences of hyperglycemia in critical illness.

PURPOSE OF REVIEW: This article reviews recent epidemiologic and intervention studies addressing the impact of hyperglycemia on morbidity and mortality in critically ill patients. It also discusses a growing body of literature examining why elevated blood glucose occurs in hospitalized patients without previously recognized diabetes. RECENT FINDINGS: Hyperglycemia is highly prevalent in the intensive care unit. Numerous observational studies have demonstrated the association between hyperglycemia and adverse outcomes, independent of pre-existing diabetes. Intervention trials of insulin therapy are limited but overall demonstrate that glucose lowering significantly improves outcomes. The ideal target for blood glucose and the population that would benefit most from intervention remain controversial. Less frequently studied than the consequences, the causes of hyperglycemia occurring during critical illness remain unclear. Although glucose abnormalities in hospitalized patients have traditionally been explained by mediators of stress, a growing body of evidence has examined whether underlying defects in glucose metabolism may also be important contributors. SUMMARY: In general, evidence suggests that hyperglycemia is a potentially correctable abnormality that has deleterious effects in critically ill individuals. Hyperglycemic patients without previously recognized diabetes appear to be particularly vulnerable, and thus further examination of the mechanisms underlying the development of elevated blood glucose is warranted.

Efficacy of thyroid hormone suppression for benign thyroid nodules: meta-analysis of randomized trials.

OBJECTIVE: To determine the efficacy of thyroid hormone suppressive therapy (THST) to decrease benign thyroid nodule volume. DESIGN: Meta-analysis. METHODS: Systematic search using electronic databases (PubMed, Medline, Cochrane Library) through August 2004, paper review, and contacting experts and drug manufacturers. Only randomized controlled studies of THST vs no treatment or placebo, for reduction of benign thyroid nodule volume, were included. Exclusion criteria were: <6-month treatment, lack of ultrasound volume measurement, and region of endemic goiter. Primary outcome was clinically relevant nodule volume reduction (>50%), with a random effects model (RevMan4.2). RESULTS: Nine randomized trials were included (609 subjects). Subjects were 88% more likely to experience >50% nodule volume reduction with THST than placebo or no treatment (relative risk = 1.88; 95% CI = 1.18-3.01; P = 0.008). However, 8 subjects must be subjected to the risk of cardiac and skeletal side effects from THST, for one to benefit from therapy (number needed to treat = 8, risk difference = 0.13; 95% CI = 0.06-0.19; P = 0.0003). Sensitivity analysis reveals that 15 null studies would have to have been missed to reverse statistical significance (fail-safe N = 15). Review of the only study with long-term treatment (5 years) suggests no significant difference in nodule volume reduction between THST and placebo. Further, studies with follow-up after THST withdrawal demonstrate rapid increase in thyroid nodule and goiter volumes. CONCLUSION: THST appears more likely than placebo or no treatment to significantly reduce benign thyroid nodule volume, but long-term treatment may be less effective and regrowth is likely following cessation of therapy. Given the risks of THST, routine use is not recommended for benign nodules.

Amiodarone-induced thyrotoxicosis and thyroid cancer: clinical, immunohistochemical, and molecular genetic studies of a case and review of the literature.

Amiodarone-induced thyrotoxicosis (AIT) is a well-known complication of amiodarone treatment found in 3% to 12% of patients. Two types of AIT have been described, each associated with a distinct histologic pattern of thyroid involvement. Type 1, which typically develops in the background of pre-existing thyroid disease, is due to iodine-induced excess thyroid hormone synthesis, whereas type 2 is due to destructive thyroiditis. The prevalence of thyroid cancer in patients with AIT is unknown. We report a case of papillary thyroid carcinoma associated with type 2 AIT.