Search

Purpose: To evaluate the association of baseline ellipsoid zone (EZ) parameters on optical coherence tomography (OCT) as calculated by a semi-automated computer algorithm with baseline visual acuity in eyes with retinal vein occlusion (RVO)., Design: Retrospective consecutive case series., Subjects: Patients affected by RVO presenting from January 2011 to December 2014., Methods: Baseline demographics, clinical characteristics, and SD-OCT data at presentation were collected. Macular cube scans were exported into a retinal layer analysis software platform and outer retinal parameters were evaluated. Outer retinal/EZ parameters included EZ-retinal pigment epithelium (RPE) volume, central foveal EZ-RPE area, EZ-RPE central subfield thickness (CST), and EZ-RPE central foveal thickness (CFT). In addition, en face EZ mapping features were extracted including percent area with EZ attenuation (i.e., EZ-RPE thickness < 20 μm) and percent area with total EZ loss (i.e., EZ-RPE thickness = 0 μm)., Main Outcome Measure: Correlation of EZ parameters and baseline visual acuity (VA). Secondary outcome measures: Correlation of EZ parameters with other clinical characteristics and OCT measures of cube volume, cube average thickness, central subfield thickness., Results: One hundred and twelve eyes were included in this analysis. Mean baseline VA was 56.53 ±17.68 ETDRS letters and was inversely associated with total EZ loss and EZ-RPE attenuation (r= - 0.33 and -0.38 respectively, p<0.001). VA was directly associated with all other EZ parameters (r=0.37 to 0.45, p<0.001). The presence of subretinal fluid was strongly linked to central parameters of central foveal EZ-RPE, EZ-RPE-CST, and EZ-RPE-CFT (Kruskal-Wallis test). Conventional OCT parameters (central subfield retinal thickness, cube volume and cube average thickness) did not have significant correlations with EZ measures (-0.30.05)., Conclusion: Baseline EZ integrity is closely linked to presenting visual acuity in eyes with RVO and macular edema. EZ mapping provides an additional metric for evaluating RVO impact on retinal anatomy and potential function.

Objective: To evaluate the incidence of new onset epilepsy and associated risk factors in patients with periodic patterns on continuous electroencephalography (cEEG) during critical illness., Methods: The local cEEG database and then medical records were reviewed from January 1, 2013 to June 30, 2013 to find adult patients with no history of epilepsy who had periodic discharges-either lateralized (LPDs) or generalized (GPDs)-or nonperiodic/nonepileptogenic (NP/NE) findings on cEEG and ≥3 months of clinical follow-up. Clinical seizure after discharge was the primary outcome. Chi-square test, Kruskal-Wallis test, and Cox proportional hazards models were used for statistical analysis., Results: A total of 195 patients (median age = 67.8 years) were included. There were 53 (27%), 73 (37%), and 69 (35%) patients with LPDs, GPDs, and NP/NE findings on cEEG, respectively. These three groups did not differ by demographic or clinical variables. A total of 29 (15%) patients (LPDs = 20 [38%], GPDs = 4 [6%], and NP/NE = 5 [7%]) developed epilepsy during a median follow-up of 32.1 (95% confidence interval [CI] = 13.2-42.8) months. The hazard ratio for epilepsy development among LPD patients was 7.7 (95% CI = 2.9-20.7) times compared to the NP/NE group, and the risk further increased to 11.4 (95% CI = 4-31.4) times if they also had electrographic seizures. This association remained significant despite adjusting for each covariate at a time., Significance: Patients with LPDs on cEEG during critical illness are at least seven times more likely to develop epilepsy compared to patients with NP/NE findings. This risk is further increased if patients with LPDs have electrographic seizures. In comparison, the presence of GPDs does not seem to impact the risk for developing epilepsy. cEEG findings at the time of acute insult have potential to serve as prognostic biomarkers for epilepsy development., (Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.)

Purpose: To investigate outer retinal parameters among patients with various chronic neurodegenerative disorders by using spectral-domain coherence tomography (OCT) in a prospective cross-sectional cohort study., Methods: A total of 132 participants were enrolled following a comprehensive diagnostic evaluation with neurologic, neuropsychology, and magnetic resonance imaging volumetric evaluations. Participants were 50 years or older, either diagnosed with Alzheimer's disease (AD) dementia, amnestic mild cognitive impairment (MCI), non-AD dementia, Parkinson's disease (PD), or age- and sex-matched controls. All participants underwent a macular cube scan for both eyes by using the Cirrus 4000 HD-OCT (Zeiss, Oberkochen, Germany). The OCT image with the best quality was selected for further analysis. Outer retinal parameters including ellipsoid zone mapping and outer nuclear layer metrics were evaluated with a novel software platform., Results: One hundred twenty-four eyes of 124 participants with AD dementia (24 eyes), amnestic MCI (22 eyes), non-AD dementia (20 eyes), PD (22 eyes), and age- and sex-matched controls (36 eyes) were included in the analysis. Eight eyes were excluded either due to the presence of macular disease or poor quality of the OCT image. The mean ages of participants were 65.9 ± 8.9 years. The outer retinal thickness measures did not show any statistical significance between the groups. However, ellipsoid zone to retinal pigment epithelium volume correlated with cognitive testing scores in all study participants., Conclusions: There were no identifiable differences in the outer retinal metrics across neurodegenerative disease groups and controls. The relationship between the degree of cognitive impairment and ellipsoid zone to retinal pigment epithelium volume warrants further study.

Background: Chest X-ray (CXR) prior to thyroid surgery continues to be routinely obtained at some institutions despite the lack of evidence for its utility. This study aimed to determine the utility of preoperative CXR in patients undergoing thyroidectomy at a single institution., Methods: In total, 594 thyroidectomy patients were included in the study. Demographics, CXR findings, anesthesia records and pathologic data were assessed. We investigated whether difficult intubation or cancer stage correlated with the presence of CXR abnormalities., Results: Of the total cohort, 83% had a preoperative CXR and 67% had cancer on surgical pathology. In total, 56% had at least one CXR abnormality, the most frequent being skeletal abnormalities (25%), followed by tracheal deviation (16%). Of 78 patients (15.8%) with tracheal deviation on CXR, only 5% had a difficult intubation. Tracheal deviation was more commonly seen in non-cancer cases compared to cancer cases (27 vs. 12%, p < 0.001). CXR impacted management in 4%. Among patients with cancer, a higher T-stage (>2) was associated with higher rate of tracheal deviation compared to T1 (17 vs. 8%, p < 0.001). While patients with non-metastatic cancer (n = 277) compared to metastatic cancer patients had a higher proportion of any abnormality on CXR (57 vs. 44%, p = 0.045), there was no significant difference for tracheal deviation, skeletal abnormalities or lung nodules. Of patients with nodules on CXR (n = 29), only 14% were found to have metastatic disease., Conclusion: The utility of preoperative CXR in patients undergoing thyroidectomy is very limited. In the climate of value-based care, routine use of this modality may be redundant and should only be ordered if clinically indicated.

Background: Patient-visitor violence (PVV) committed against nurses is a worldwide problem. Registered nurses in emergency departments (EDs) are particularly susceptible. The frequency and severity of PVV against emergency nurses (ENs) internationally is well documented. Little is known about factors that make ENs feel safe from PVV., Aim: Examine the psychometric properties of the Personal Workplace Safety Instrument for Emergency Nurses (PWSI-EN), developed to measure ENs' perceptions of safety from PVV., Methods: Instrument development was based on a literature review, input from ENs, and expert opinion. An online version of the PWSI-EN was distributed to a convenience sample of ENs practicing in EDs across the United States. Psychometric testing included measures of internal consistency reliability, construct validity to support subscales, and comparisons on demographic variables., Results: Three-hundred and five (N = 305) ENs from 16 hospitals responded to the original 31-item PWSI-EN. Based on item analysis and exploratory factor analysis (EFA), the instrument was reduced to 23 items with Cronbach's α = .912. EFA delineated six subscales relevant to perception of safety from PVV with factor loadings from .342 to .879. Low to moderate subscale correlations showed a degree of independence for concept domains. Known groups approach for construct validity revealed statistically significant differences (p < .05) for five subscales and the total score between community and academic or teaching hospitals. Hospital type, organizational confidence, and fear for patient safety were significant predictors of greater perceptions of safety from PVV., Linking Evidence to Action: The PWSI-EN is a valid and reliable survey instrument to assess EN perceptions of safety. ED and hospital leaders can use this instrument to determine specific areas to focus efforts in order to improve ENs' perception of safety from PVV. Researchers exploring interventions aimed at improving perceptions of safety from PVV for ENs may find the PWSI-EN useful., (© 2017 Sigma Theta Tau International.)

Background: The frequency of variable hormonogenesis in patients with Cushing disease (CD) but without cyclical symptoms is unclear., Aim: To assess the frequency of variable hormonogenesis in patients presenting with CD., Methods: Over a 6-month period, patients with confirmed or suspected CD provided late-night salivary samples for up to 42 consecutive nights., Results: Of 19 patients confirmed to have CD, 16 provided at least 7 consecutive salivary samples, and 13 provided at least 21; these 16 patients are the subjects of this report. Twelve patients had at least three peak and two trough levels of late-night salivary cortisol (LNSC) but in only two patients were strict criteria for cyclical hormonogenesis fulfilled; variation was assessed as random in the others. Eight patients had de novo CD, and eight had recurrent/persistent disease. All patients with recurrent/persistent CD had two or more normal results, and in four of these patients, >50% of LNSC were normal. In six patients with de novo disease with at least one normal LNSC level, the maximum levels ranged from 1.55 to 15.5 times the upper limit of normal., Conclusions: Extreme fluctuations of cortisol production, measured by sequential LNSC, are common in CD. In newly diagnosed disease, this may only occasionally impair diagnostic ability, whereas in most patients with recurrent/persistent disease after pituitary surgery, LNSC is frequently within the reference range, with potential to cause diagnostic problems.

Background: Music therapy (MT) research has demonstrated positive effects on fatigue, depressed mood, anxiety, and pain in perioperative care areas. However, there has been limited research on the effects of MT for surgical patients on orthopaedic units., Purpose: The purpose of this study was to understand the impact of MT sessions on post-elective orthopaedic surgery patients' pain, mood, nausea, anxiety, use of narcotics and antiemetics, and length of stay., Methods: This was a randomized controlled study with an experimental arm (MT sessions) and a control arm (standard medical care). Patients received MT within 24 hours of admission to the unit, as well as every day of their stay. Same-day pre- and postdata were collected 30 minutes apart for both arms, including patient self-reported mood, pain, anxiety, and nausea. Use of medications and length of stay were gleaned from the electronic medical record., Results: Data were obtained for 163 patients, age 60.5 ± 11.1 years, 56% of whom were male. Joints targeted by surgeries were hips (54%), knees (42%), and shoulders (4%). There were significantly greater changes favoring the MT group on Day 1 (pain, anxiety, and mood), Day 2 (pain, anxiety, mood, and nausea), and Day 3 (pain, anxiety, and mood). Among participants with a pre-pain score of 2 or more on Day 1, a decrease of at least 2 points was noted in 36% of the MT group and 10% of the control group (P < .001). Overall, 73% of MT patients versus 41% of control patients reported improved pain (P < .001). No significant between-group differences in medications or length of stay were noted., Conclusions: We observed greater same-day improvements of pain, emotional status, and nausea with MT sessions, compared to usual care, in patients hospitalized after elective orthopaedic surgeries. Effects on narcotic and antiemetic usage, as well as length of stay, were not observed. More research needs to be conducted to better understand the benefits of MT pre- and post-elective orthopaedic surgery.

Study Objectives: Although continuous positive airway pressure (CPAP) therapy is regarded as the gold standard treatment for obstructive sleep apnea (OSA) in adults, outcomes in older patients are limited. This study examines the effect of CPAP therapy in older adults with OSA (older than 60 years) compared to younger adults (age 18 to 60 years) to inform the current standard of practice., Methods: We performed a retrospective study with a convenience sample to compare responses to CPAP treatment in older versus younger adults with OSA using validated, patient-reported outcomes (PROs). A total of 532 patients were analyzed at baseline and at 3, 6, and 12 months after CPAP initiation. The effects of CPAP adherence and OSA severity on PRO scores were measured in each age group., Results: Patients older than 60 years had higher apnea-hypopnea indices but lower Epworth Sleepiness Scale (ESS), Fatigue Severity Scale (FSS), and Patient Health Questionnaire-9 (PHQ-9) scores and higher Functional Outcomes of Sleep Questionnaire (FOSQ) scores at baseline compared to patients age 18 to 60 years. At 1 year after CPAP initiation, significant and comparable improvements in ESS, FSS, PHQ-9, and FOSQ scores were observed in patients older than 60 years relative to younger patients. When stratifying by OSA severity, change between age groups was significantly different only for PHQ-9 in patients with mild OSA, with greater improvements observed in younger patients., Conclusions: This study adds to the limited data on treatment outcomes with CPAP therapy in older adults with OSA. Patients older than 60 years achieve improvement in sleepiness, fatigue, depressive symptoms, and quality of life analogous to that of younger adults., (© 2018 American Academy of Sleep Medicine)

Context: Hyperglycemia plays a key role in the pathogenesis of cardiovascular complications of diabetes. Type 2 diabetes mellitus (T2DM) is associated with high-density lipoprotein (HDL) dysfunction and increased degradation of apolipoprotein I (ApoAI). The mechanism(s) of these changes is largely unknown., Objective: To study the role of hyperglycemia-induced glycation on ApoAI kinetics and stability in patients with diet-controlled T2DM., Design: 2H2O-metabolic labeling approach was used to study ApoAI turnover in patients with diet-controlled T2DM [n = 9 (5 F); 59.3 ± 8.5 years] and matched healthy controls [n = 8 (4 F); 50.7 ± 11.6 years]. The effect of Amadori glycation on in vivo ApoAI stability and the antioxidant and cholesterol efflux properties of HDL were assessed using a proteomics approach and in vitro assays., Results: Patients with T2DM had increased turnover of ApoAI and impaired cholesterol efflux and antioxidant properties of HDL. Glycated hemoglobin was negatively correlated with the half-life of ApoAI and cholesterol efflux function of HDL. Proteomics analysis identified several nonenzymatic early (Amadori) glycations of ApoAI at lysine sites. The kinetics analysis of glycated and native ApoAI peptides in patients with T2DM revealed that glycation resulted in a threefold shorter ApoAI half-life., Conclusions: The 2H2O method allowed the detection of early in vivo impairments in HDL metabolism and function that were related to hyperglycemia-induced glycation of ApoAI in T2DM., (Copyright © 2017 Endocrine Society)

Hypogonadism frequently occurs in male patients with type 2 diabetes (T2DM) and is linked to insulin resistance and inflammation. Testosterone levels rise acutely in obese patients following bariatric surgery, though long-term changes have not been investigated in a randomized controlled trial. This study evaluated obese men with T2DM randomized to either bariatric surgery or medical therapy. Testosterone, gonadotropins, body composition, insulin sensitivity, and inflammatory markers were evaluated in 32 patients at baseline and at 5 years. Surgical patients had 47.4% increase in free testosterone compared to medical therapy patients who had 2.2% decrease (P = 0.013). Increase in free testosterone correlated with reduction in body weight, high-sensitivity C-reactive protein (hsCRP), and leptin levels. Prolonged improvements in testosterone levels after bariatric surgery in T2DM are found to be related to reduction in body weight and adipogenic inflammation.

Background: Although randomized trials demonstrate the noninferiority of rivaroxaban compared with warfarin in the context of nonvalvular atrial fibrillation (AF), little is known about how these drugs compare in practice., Objective: To assess the relative effectiveness and safety of rivaroxaban versus warfarin in a large health system and to evaluate this association by time in therapeutic range (TTR)., Methods: We conducted a retrospective cohort study with propensity matching in the Cleveland Clinic Health System. The study included patients initiated on warfarin or rivaroxaban for thromboembolic prevention in nonvalvular AF between January 2012 and July 2016. The main outcomes were thromboembolic events and major bleeds. Analyses were stratified by warfarin patients' TTR., Results: The cohort consisted of 472 propensity-matched pairs. The mean age was 73.6 years (SD = 11.7), and the mean CHADS 2 score was 1.8. The median TTR for warfarin patients was 64%. In the propensity-matched analysis, there was no significant difference in thromboembolic or major bleeding events between groups. Among warfarin patients with a TTR <64% and their matched rivaroxaban pairs, there was also no significant difference in thromboembolic or major bleeding events., Conclusions: Under real-world conditions, warfarin and rivaroxaban were associated with similar safety and effectiveness, even among those with suboptimal therapeutic control. Individualized decision making, taking into account the nontherapeutic tradeoffs associated with these medications (eg, monitoring, half-life, cost) is warranted.

Background: There is a paucity of studies on transitions from IV insulin infusion (IVII) to subcutaneous (SC) insulin in the medical ICU (MICU)., Methods: We conducted a retrospective study of patients admitted to the Cleveland Clinic MICU from June 2013 to January 2014 who received IVII. We compared blood glucose (BG) control between 3 cohorts based on timing of basal insulin dose: (1) NB (no basal), (2) IB (incorrect basal), (3) CB (correct basal) at 5 time points post-IVII discontinuation (1, 4, 8, 12, and 24h). Insulin doses used for transitioning were compared with 80% of estimated 24h IVII total. Analysis was done using chi-square, ANOVA and t-tests., Results: There were 269 patients (NB 166, IB 45, CB 58), 55% male with a mean age 58±16years. 103 patients (38%) had a transition attempted (IB 21%, CB 17%). The NB cohort had better BG than the IB cohort at all time points (p<0.001) but also lower HbA1c, prior DM diagnosis and home insulin use (p<0.001). IB and CB did not have significantly different BG with mean BG>180mg/dL at 4/5 time intervals. However, the dose of basal insulin used was less than 80% of estimated 24h IVII total (IB 21.4 vs 49.6U, CB 25vs 57.1U). Despite this, 15% of patients in the IB cohort and 24% of patients in the CB had hypoglycemic events., Conclusion: The low rates of IV to SC insulin transitions raises the question of challenges to transitions., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Type 2 diabetes mellitus (T2DM) is associated with oxidative stress and perturbed iron metabolism. Serotransferrin (Trf) and ceruloplasmin (Cp) are two key proteins involved in iron metabolism and anti-oxidant defense. Non-enzymatic glycation and oxidative modification of plasma proteins are known to occur under hyperglycemia and oxidative stress. In this study, shotgun proteomics and 2 H 2 O-based metabolic labeling were used to characterize post-translational modifications and assess the kinetics of Trf and Cp in T2DM patients and matched controls in vivo. Six early lysine (Amadori) and one advanced arginine glycation were detected in Trf. No glycation, but five asparagine deamidations, were found in Cp. T2DM patients had increased fractional catabolic rates of both Trf and Cp that correlated with HbA 1c (p < 0.05). The glycated Trf population was subject to an even faster degradation compared to the total Trf pool, suggesting that hyperglycemia contributed to an increased Trf degradation in T2DM patients. Enhanced production of Trf and Cp kept their levels stable. The changes in Trf and Cp turnover were associated with increased systemic oxidative stress without any alteration in iron status in T2DM. These findings can help better understand the potential role of altered Trf and Cp metabolism in the pathogenesis of T2DM and other diseases., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: The objective of the study was to investigate the effects of lacosamide (LCM) on daytime sleepiness ascertained by the Epworth Sleepiness Scale (ESS) in adults with focal epilepsy in a randomized, controlled design., Methods: Subjects taking ≤2 AEDs for ≥4weeks underwent polysomnography with EEG followed by the maintenance of wakefulness test (MWT) and completed the ESS and other patient-reported outcomes (PROs) at baseline, LCM 200mg/day, and LCM 400mg/day (Visit 4; V4). Primary endpoint was ESS change (V4 to baseline) between LCM and placebo. Noninferiority test on ESS used a one-sided t-test based on a hypothesized difference of 4-point change between groups. Superiority test used a two-sided t-test to investigate the difference in change in PROs and MWT mean sleep latency (MSL) between groups. Fifty-five subjects provided 80% power to show noninferiority of LCM assuming 10% dropout., Results: Fifty-two subjects (mean age: 43.5±13.2years, 69% female, median monthly seizure frequency: 1 [0, 4.0]) participated. Baseline group characteristics including age, sex, ethnicity, standardized AED dose, seizure frequency, and ESS were similar. Abnormal baseline ESS scores were found in 35% of subjects. Noninferiority test found a ≤4-point increase in ESS (mean [95% CI]) in LCM subjects vs. placebo (-1.2 [-2.9, 0.53] vs. -1.1 [-5.2, 3.0], p=0.027) at V4. No significant difference in change in PROs, MSL, seizure frequency, or AED standardized dose was observed between groups., Significance: Our interventional trial found that LCM is not a major contributor to daytime sleepiness based on subjective and objective measures. Inclusion of sleepiness measures in AED trials is warranted given the high prevalence of sleep-wake complaints in people with epilepsy., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Ineffective or inefficient transitions threaten patient safety, hinder communication, and worsen patient outcomes. The Hospital Culture of Transitions (H-CulT) survey was designed to assess a hospital's organizational culture related to within-hospital transitions in care involving patient movement. In this article, psychometric properties of the H-CulT survey were examined to assess and refine the hospital culture of transitions., Methods: A cross-sectional, multicenter, multidisciplinary correlational design and survey methods were used to examine the psychometric properties of the H-CulT survey. Exploratory factor analysis was used to quantify the accuracy of the previously identified structure. Specifically, the analysis involved the principal axis factor method with an oblique rotation, based on a polychoric correlation matrix., Results: A sample of 492 respondents from 13 diverse hospitals participated. Cronbach's alpha for the instrument was 0.88, indicating strong internal consistency. Seven subscales emerged and were labeled: Hospital Leadership, Unit Leadership, My Unit's Culture, Other Units' Culture, Busy Workload, Priority of Patient Care, and Use of Data. Correlations between subscales ranged from 0.07 to 0.52, providing evidence that the subscales did not measure the same construct. Subscale correlations with the total score were near or above 0.50 (p <0.001). Use of a factor-loading cutoff of 0.40 resulted in the elimination of 12 items because of weak associations with the topic., Conclusion: The H-CulT is a psychometrically sound and practical survey for assessing hospital culture related to patient flow during transitions in care. Survey results may prompt quality improvement interventions that enhance in-hospital transitions and improve staff satisfaction and patient satisfaction with care., (Copyright © 2017 The Joint Commission. Published by Elsevier Inc. All rights reserved.)

Purpose: The appropriate cosyntropin dose during cosyntropin stimulation tests remains uncertain. We conducted a prospective, randomized pilot study to compare 1 μg IV low dose cosyntropin test, 25 μg IM medium dose cosyntropin test, and 250 μg IM standard dose cosyntropin test to evaluate secondary adrenal insufficiency. Insulin tolerance test was used as the gold standard., Method: The study included patients with hypothalamic/pituitary disease (n  = 10) with at least one pituitary axis deficiency other than ACTH deficiency and controls (n  = 12). All tests were done in random order. Sensitivity and specificity were calculated for total cortisol and serum free cortisol cut-off levels during cosyntropin stimulation tests., Results: The median (range) age and F/M sex ratios for patients and controls were 54 years (23-62), 2/8, and 33 years (21-51), 6/6, respectively. The best total cortisol cut-off during low dose cosyntropin test, medium dose cosyntropin test, 30 min and 60 min standard dose cosyntropin test were 14.6 μg/dL (100% sensitivity & specificity), 18.7 μg/dL (100% sensitivity, 88% specificity), 16.1 (100% sensitivity & specificity), and 19.5 μg/dL (100% sensitivity & specificity), respectively. There was no difference in the ROC curve for cortisol values between the cosyntropin stimulation tests (p  > 0.41). Using a cortisol cut-off of 18 μg/dL during cosyntropin stimulation tests, only cortisol level at 30 min during standard dose cosyntropin test provided discrimination similar to insulin tolerance test. The best peak free cortisol cut-off levels were 1 μg/dL for insulin tolerance test, 0.9 μg/dL for low dose cosyntropin test, 0.9 μg/dL for medium dose cosyntropin test, and 0.9 μg/dL and 1.3 μg/dL for 30 min and 60 min standard dose cosyntropin test, respectively., Conclusion: All cosyntropin stimulation tests had excellent correlations with insulin tolerance test, when appropriate cut-offs were used. This pilot study does not suggest an advantage in using 25 μg cosyntropin dose during the cosyntropin stimulation test. A serum free cortisol cut-off of 0.9 μg/dL may be used as pass criterion during low dose cosyntropin test, standard dose cosyntropin test cosyntropin test, and 30 min standard dose cosyntropin test.

Background: Parkinson disease (PD) is associated with a high prevalence of insomnia, affecting up to 88% of patients. Pharmacotherapy studies in the literature addressing insomnia in PD reveal disappointing and inconsistent results. Cognitive behavioral therapy (CBT) is a novel treatment option with durable effects shown in primary insomnia. However, the lack of accessibility and expense can be limiting. For these reasons, computerized CBT for insomnia (CCBT-I) has been developed. The CCBT-I program is a 6-week web-based course consisting of daily "lessons" providing learnable skills and appropriate recommendations to help patients improve their sleep habits and patterns., Methods: We conducted a single-center, pilot, randomized controlled trial comparing CCBT-I versus standardized sleep hygiene instructions to treat insomnia in PD. Twenty-eight subjects with PD experiencing insomnia, with a score > 11 on the Insomnia Severity Index (ISI) were recruited. Based on a 6-point improvement in ISI in treatment group when compared to controls and an alpha = 0.05 and beta of 0.1 (power = 90%) a sample size of 11 patients (on active treatment) were required to detect this treatment effect using a dependent sample t-test., Results: In total, 8/14 (57%) subjects randomized to CCBT-I versus 13/14 (93%) subjects randomized to standard education completed the study. Among completers, the improvement in ISI scores was greater with CCBT-I as compared to standard education (-7.9 vs -3.5; p  = 0.03). However, in an intention-to-treat analysis, where all enrolled subjects were included, the change in ISI between groups was not significant (-.4.5 vs -3.3; p  = 0.48), likely due to the high dropout rate in the CCBT-I group (43%)., Conclusion: This pilot study suggests that CCBT-I can be an effective treatment option for PD patients with insomnia when the course is thoroughly completed. High drop-out rate in our study shows that although effective, it may not be a generalizable option; however, larger studies are needed for further evaluation.

Context: Transsphenoidal surgery (TSS) to resect a pituitary adenoma is considered first-line treatment for patients with Cushing's disease (CD). Early, post-operative remission rates >80% are expected for patients with a microadenoma (≤ 10 mm) visible on magnetic resonance (MR) imaging., Objective: To report surgical outcomes and predictors of remission in a specialist center for patients with CD., Patients and Methods: Clinical data was obtained from a prospective CD database in addition to review of all electronic medical, laboratory and surgical patient records. Patients who underwent their first TSS by one neurosurgeon between 2004 and 2013, and had a minimum 1 year follow up, were evaluated., Results: One hundred and one consecutive patients with CD (73F, 28M) underwent TSS. Median (range) age and follow-up were 47 (15-87) and 4.33 (1-9.8) years, respectively. At surgery, 74 (73.2%) patients had a microadenoma, 27 a macroadenoma; six of the latter patients had a planned, subtotal resection to control neurological signs due to mass effect. Initial remission rates were: microadenoma, 89% (66/74); macroadenoma, 63% (17/27); and 81% (17/21) in those macroadenomas where complete surgical removal was anticipated. Initial non-remission occurred in 18 patients, ten macro- and eight microadenoma; six of 18 had residual disease on most recent follow up. Six (2 macro, 4 micro) of the 83 patients with initial remission have had late (>12 months) recurrence of hypercortisolism that required either repeat TSS or adjunctive therapy, three of whom have persistent hypercortisolism. Macroadenoma (p = 0.003) and tumor invasion beyond the pituitary and sella (p < 0.001) were associated with failure to obtain remission with the initial TSS and greater likelihood of late recurrence. Patients in whom no lesion was seen on neuroimaging had rates of initial remission (21/25 or 84%) and a similar late recurrence rate of 4% (1/25) in comparison with those with MR-visible microadenomas (3/49, or 6%)., Conclusions: A team-based approach, in a specialized pituitary center, can lead to initial and durable, long-term remission in patients with CD. The presence of a macroadenoma and tumor extension beyond the pituitary and sella were predictive of initial non-remission as well as risk of late recurrence.

Background: Insomnia is a common complaint of individuals presenting to healthcare providers and is associated with decreased quality of life and higher healthcare utilization. In-person cognitive behavioral therapy (CBT) is an effective treatment for insomnia but is hindered by cost and limited access to treatment. Initial research suggests that Web-based CBT may mitigate these obstacles., Introduction: This study tests the effectiveness of a Web-based program for insomnia based on principles of CBT and stress management., Materials and Methods: We conducted a randomized trial with wait-list controls among adults with primary insomnia (n = 88). Two hundred sixty-three adults with comorbid insomnia were also included and analyzed separately. The intervention was a 6-week online program, and effectiveness was measured via the Insomnia Severity Index (ISI)., Results: Baseline ISI score for the intervention group (n = 43) was 17.0; 16.6 for the control group (n = 45). At first follow-up, the intervention group (n = 25) had a mean change from baseline of -7.3 (95% CI: -9.0, -5.6), sustained through second follow-up, while the control group (n = 35) had a change of -1.3 (-2.7, 0.1). The between-group difference was statistically significant (p < 0.001). Participants in the comorbid insomnia group had a baseline ISI score of 16.7 with improvement similar to the primary insomnia group (-6.9; -7.6, -6.2)., Discussion: We observed clinically meaningful improvements in insomnia severity in adults with primary or comorbid insomnia. Sustained improvement over 4 months underscores the effectiveness of a well-constructed online CBT for insomnia program., Conclusions: Go! to Sleep, (© offers a potentially effective treatment option for adults with insomnia by eliminating geographical barriers to care.)

Objective: Weight-loss maintenance following very-low-calorie meal plans is poorly studied. This report describes weight-loss efficacy and predictors of weight-loss maintenance of a ketogenic, very-low-calorie meal plan (protein-sparing modified fast, PSMF) in people with obesity., Methods: A total of 127 consecutive adults in the PSMF meal plan (27.2 ± 19.5 weeks) and 48 adults on a conventional, hypocaloric meal plan (23.6 ± 20.8 weeks) were retrospectively studied for percent weight change from baseline to end of intervention and at 6, 12, and 24 months postintervention. Baseline factors were analyzed for correlations with weight-loss maintenance., Results: At end of intervention, weight loss from baseline was greater for the PSMF group compared to the conventional intervention group (-12.4% vs. -2.6%; P<.001) but was similar between groups by 12 months postintervention. PSMF subjects who attended follow-up visits to receive instruction on gradual and limited carbohydrate refeeding after ketosis saw significant weight loss at the end of PSMF compared to those who did not follow-up to receive instruction (-17.5% vs. -8.0%; P<.001) and maintained greater weight loss through 12 months post-PSMF (-9.8% vs. -1.5%; P<.001). Higher baseline body mass index correlated with less weight loss at 12 months post-PSMF (P = .035)., Conclusion: PSMF results in effective short-term weight loss of more than 5% from baseline weight. Follow-up for limited carbohydrate refeeding instruction is important for weight-loss maintenance up to 2 years after initial weight loss., Abbreviations: BMI = body mass index; PSMF = protein-sparing modified fast.

Background: Because the interrelationships of objectively ascertained sleep-disordered breathing (SDB), postcardiac surgery atrial fibrillation (PCSAF), and obesity remain unclear, we aimed to further investigate the interrelationships in a clinic-based cohort., Methods: Patients with polysomnography and cardiac surgery (coronary artery bypass surgery and/or valvular surgery) within 3 years, from January 2009 to January 2014, were identified, excluding those with preexisting atrial fibrillation. Logistic models were used to determine the association of SDB (apnea hypopnea index [AHI] per 5-unit increase) and secondary predictors (central sleep apnea [CSA] [central apnea index ≥ 5] and oxygen desaturation index [ODI]) with PCSAF. Models were adjusted for age, sex, race, BMI, and hypertension. Statistical interaction and stratification by median BMI was performed. ORs and 95% CIs are presented., Results: There were 190 patients who comprised the analytic sample (mean age, 60.6 ± 11.4 years; 36.1% women; 80% white; BMI, 33.3 ± 7.5 kg/m 2 ; 93.2% had an AHI ≥ 5; 30% had PCSAF). Unlike unadjusted analyses (OR, 1.06; 95% CI, 1.01-1.1), in the adjusted model, increasing AHI was not significantly associated with increased odds of PCSAF (OR, 1.04; 95% CI, 0.98-1.1). Neither CSA nor ODI was associated with PCSAF. A significant interaction with median BMI was noted (P = .015). Effect modification by median BMI was observed; those with a higher BMI > 32 kg/m 2 had 15% increased odds of PCSAF (OR, 1.15; 95% CI, 1.05-1.26; P < .003)., Conclusions: SDB was significantly associated with PCSAF in unadjusted analyses, but not after taking into account obesity; those with both SDB and obesity may represent a vulnerable subgroup to target to reduce PCSAF and its associated morbidity., (Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Purpose: To compare the rates of tumour recurrence following episcleral brachytherapy for uveal melanoma before and after implementation of intraoperative echographic confirmation of plaque placement., Materials and Methods: All patients with primary single ciliary body or choroidal melanoma treated with iodine-125 or ruthenium-106 plaque brachytherapy between 1 January 2004 and 30 December 2013 were included. Exclusion criteria were patients with previous radiation treatment and patients who received adjuvant transpupillary thermotherapy. Since February 2007, intraoperative echographic confirmation was initiated to ensure that the plaque was centred on the tumour base and/or all tumour margins were covered by the plaque., Results: 252 patients were included in the study. Local tumour control after primary brachytherapy was achieved in 242/252 (96.0%). Of the 10 patients with treatment failure, 8 patients had local recurrence and 2 patients had failure to response. With the incorporation of the intraoperative echographic confirmation for plaque positioning the treatment failure rate decreased from 9.3% (5/54 patients) to 1.5% (3/198 patients). Continuous and categorical univariable predictors of recurrence were analysed for statistical significance. The only statistically significant variable was the intraoperative echographic confirmation (HR: 0.16; p=0.032) for recurrence within the first 24 months., Conclusions: Intraoperative echographic confirmation of plaque placement during episcleral brachytherapy for choroidal melanoma reduces the risk of early local recurrence., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Purpose: To evaluate the short-term safety and efficacy of topical difluprednate (0.05%) for the treatment of noninfectious uveitic cystoid macular edema., Methods: Twenty-seven patients (35 eyes) undergoing treatment with difluprednate 4 times daily for 3 weeks for noninfectious uveitic cystoid macular edema were reviewed for visual acuity, intraocular pressure, optical coherence tomography, and fluorescein angiography results. A mixed model analysis was fit with each measure as the outcome, visit as the primary predictor, and patient and eye as random effects., Results: Mean central foveal thickness decreased by 117 μm (P < 0.001) at 30 ± 15 days, 124 μm (P < 0.001) at 60 ± 15 days, and 152 μm (P < 0.001) at 180 ± 30 days. Complete resolution of intraretinal fluid was observed in 15 of 34 (44%) eyes at 30 ± 15 days, 11 of 21 (52%) eyes at 60 ± 15 days, and 9 of 12 (75%) eyes at 180 ± 30 days. Improvement in fluorescein leakage was noted in 7 of 8 eyes (88%). Visual acuity improved by a mean of 5 letters (P = 0.001) at 30 ± 15 days, 5.5 letters (P = 0.007) at 60 ± 15 days, and 7 letters (P = 0.032) at 180 ± 30 days. Mean increase in intraocular pressure was 1.48 mmHg at 30 ± 15 days (P = 0.080), 1.92 mmHg at 60 ± 15 days (P = 0.110), and 6.18 mmHg (P = 0.001) at 180 ± 30 days., Conclusion: Topical difluprednate is a well-tolerated and effective treatment for noninfectious uveitic cystoid macular edema with decreased central foveal thickness, mild improvement in visual acuity, and elevation of intraocular pressure observed in a few patients.

Purpose: To evaluate the patterns, the risk factors, and the management of recurrence following brachytherapy in patients with posterior uveal melanoma, given that an understanding of the recurrence patterns can improve early recognition and management of local treatment failure in such patients., Design: Retrospective cohort study., Methods: Setting: Multispecialty tertiary care center., Participants: A total of 375 eyes treated with episcleral brachytherapy for posterior uveal melanoma from January 2004 to December 2014. Exclusion criteria included inadequate follow-up (<1 year) and previous radiation therapy. Main Outcomes and Measures: Local control rate and time to recurrence were the primary endpoints. Kaplan-Meier estimation and Cox proportional hazards models were conducted to identify risk factors for recurrence., Results: Twenty-one patients (5.6%) experienced recurrence (follow-up range 12-156 months; median 47 months). The median time to recurrence was 18 months (range 4-156 months). Five-year estimated local recurrence rate was 6.6%. The majority (90.5%) of the recurrences occurred within the first 5 years. The predominant site of recurrence was at the tumor margin (12 patients, 57.1%). Univariate analysis identified 3 statistically significant recurrence risk factors: advanced age, largest basal diameter, and the use of adjuvant transpupillary thermotherapy (TTT). Recurrent tumors were managed by repeat brachytherapy, TTT, or enucleation., Conclusions: Local recurrences following brachytherapy are uncommon 5 years after episcleral brachytherapy. Follow-up intervals can be adjusted to reflect time to recurrence. Most of the eyes with recurrent tumor can be salvaged by conservative methods., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: Endocrinologists are faced with a growing elderly patient population with diabetes mellitus (DM), some of whom are in skilled nursing facilities (SNFs). Efforts at managing their DM is hampered by concerns for hypoglycemia. This study aimed to determine the frequency of hypo- and hyperglycemia in SNFs, and associated factors., Methods: We reviewed medical records of 200 consecutive residents admitted to two SNFs in the Cleveland area in 2014 with documented DM, aged ≥65 years. Data collected included blood glucose (BG) levels and DM regimens. Frequency of hyper- and hypoglycemic events was noted. Since patients had different frequencies of BG checks, event-days were calculated., Results: Mean age, BG, and glycated hemoglobin (±SD) were as follows: 80.2 ± 8.2 years, 172.4 ± 40.3 mg/dL, and 7.5 ± 1.9% (59 mmol/mol), respectively. Seventy-one percent were on insulin alone, 15.5% on insulin and oral diabetes agents, and 13.5% on oral diabetes agent on admission. Patients with at least one event were as follows: 38% hypoglycemia, 3.5% severe hypoglycemia, 90.5% hyperglycemia, and 15% severe hyperglycemia. Event-days were: 3.4% hypoglycemia and 52.4% hyperglycemia. Risk of hypoglycemia was highest with concomitant sulfonylurea and prandial or sliding-scale insulin. Hyperglycemia risk was high in basal insulin-containing regimens., Conclusion: Hypoglycemia was seen in one-third of patients, and hyperglycemia was common despite insulin use. Concomitant use of sulfonylurea and prandial or sliding-scale insulin is best avoided in this fragile population with hypo- and hyperglycemia., Abbreviations: ADA = American Diabetes Association BG = blood glucose DM = diabetes mellitus GLP-1 = glucagon-like peptide 1 HBA1c = glycated hemoglobin LOS = length of stay NPH = neutral protamine Hagedorn SNF = skilled nursing facility SSI = sliding-scale insulin.

Background: The EuroQol 5 dimensions questionnaire (EQ-5D), Patient-Reported Outcomes Measurement Information System (PROMIS) 10 Global Health, and Veterans RAND 12-Item Health Survey (VR-12) are generic patient-reported outcome (PRO) questionnaires that assess a patient's general health. In choosing a PRO to track general health status, it is necessary to consider which measure will be the most responsive to change after treatment. To date, no studies exist comparing responsiveness among the EQ-5D, PROMIS 10 Global Health, and the Veterans Rand 12-Item Health Survey (VR-12)., Purpose: To determine which of the generic PROs are most responsive internally and externally in the setting of knee arthroscopy., Study Design: Cohort study (diagnosis); Level of evidence, 3., Methods: Fifty patients who underwent knee arthroscopy were surveyed preoperatively and a mean 3.6 months postoperatively, with 90% follow-up. PROs included the EQ-5D, EQ-5D visual analog scale, PROMIS 10 Global Health (PROMIS 10) physical and mental components, VR-12 physical and mental components, and the Knee injury and Osteoarthritis Outcome Score (KOOS)-pain subscale. Internal responsiveness was evaluated by performing paired t tests on the changes in measures and calculating 2 measures of effect size: Cohen d and standardized response mean (SRM). External responsiveness was evaluated by comparing Pearson correlation measures between the disease-specific reference KOOS-pain and generic PROs., Results: For internal responsiveness, 3 PROs showed a statistically significant improvement in score after treatment (EQ-5D: +0.10 [95% CI, 0.06-0.15], VR-12 physical: +7.2 [95% CI, 4.0-10.4]), and PROMIS 10 physical: +4.4 [95% CI, 2.6-6.3]) and effect size statistics with moderate change (Cohen d and SRM, 0.5-0.8). Assessing external responsiveness, a high correlation with the disease-specific reference (KOOS-pain score) was found for EQ-5D (0.65), VR-12 physical (0.57), and PROMIS 10 physical (0.77). For both internal and external responsiveness, the EQ-5D, VR-12 physical, and PROMIS 10 physical showed significantly greater responsiveness compared with the other general PRO measures but no statistical differences among themselves., Conclusion: There is no statistical difference in internal or external responsiveness to change among the EQ-5D, VR-12 physical, and PROMIS 10 physical instruments. In tracking longitudinal patient health, researchers and administrators have the flexibility to choose any of the general PROs among the EQ-5D, VR-12 physical, and PROMIS 10 physical. We recommend that any study tracking PROs in knee arthroscopy include 1 of these generic instruments., Competing Interests: The authors declared that they have no conflicts of interest in the authorship and publication of this contribution.

Background: Patch testing is the gold standard for diagnosing allergic contact dermatitis in children., Objective: To present a 10-year retrospective review of pediatric patch testing at our institution., Methods: Data from patients 18 years or younger who presented for patch testing from February 1, 2005, to May 31, 2015, were entered into a database. Patch testing was performed according to North American Contact Dermatitis Group standards. A positive reaction was defined as any allergen for which the patient had a 1+ or greater reaction and provided avoidance information., Results: A total of 157 patients with a mean (SD) age of 12.3 (4.1) years were evaluated. The 2 most frequent allergens were nickel and cobalt. Most patients were referred by dermatologists for suspected allergic contact dermatitis (72.3%). Dermatitis was present for more than 2 years in most cases (n = 67 [46.2%]), from 6 months to 2 years (n = 49 [33.8%]), and for less than 6 months (n = 29 [20.0%]). Males were more likely to have a positive reaction to fragrance mix 1 compared with females (P = .02). No significant association was found between age and allergen sensitivity. Those with a history of atopy were more likely to have a positive reaction to cobalt (P = .008) and chromium (P = .03). Sixty patients (38.2%) returned for follow-up, and 37 (60.7%) reported improvement; most (n = 54 [88.5%]) were being treated with topical corticosteroids., Conclusion: Our study of pediatric patch testing can provide information regarding common allergens in children, which can enhance patient care. Primary care practitioners may benefit from awareness of patch testing as an alternative to prescribing systemic immunosuppressants., (Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: To determine whether 12 months of intensive medical therapy (IMT) improves HDL functionality parameters in subjects with type II diabetes (T2D)., Methods: Retrospective, randomized, and controlled 12-month IMT intervention trial that enrolled 13-subjects with T2D (age 51- years, fasting glucose 147 mg/dL, body mass index [BMI] 36.5 kg/m(2)) and nine healthy control (46-years, fasting glucose 90 mg/dL, BMI 26.5 kg/m2). Subjects with T2D underwent IMT and HDL functionality measures (pro-inflammatory index of high-density lipoprotein (pHDL)), paraoxonase one (PON1), ceruloplasmin (Cp), and myeloperoxidase (MPO) activity were performed on samples at baseline and at 12-months following IMT., Results: At baseline, pHDL index was significantly higher in subjects with T2D (p < 0.001) and apolipoprotein A-1 levels were significantly lower (p = 0.013) vs., Controls: After 12-months, there was a trend for improved pHDL activity (p = 0.083), as indicated by intent-to-treat analysis, but when the non-adherent subject was omitted (per-protocol), significant attenuations in pHDL activity (p = 0.040) were noted; Δ pHDL activity at 12-months was associated with Δ weight (r = 0.62, p = 0.032) and Δ fasting glucose (r = 0.65, p = 0.022). Moreover, PON1 activity significantly improved (p < 0.001). The aforementioned occurred in association with improvements in inflammatory markers (i.e., C-reactive protein & tumor necrosis factor), hemoglobin A1C, fasting glucose, triglycerides, high-density lipoprotein levels and adipokines., Conclusion: IMT ameliorates pHDL index and significantly improves anti-oxidative function, as measured by PON1. Improvements in weight and fasting glucose mediated the decrease in pHDL index. Pharmacological aids and lifestyle modification are required to improve cardiovascular risk factors, subsequent mortality risk, and promote T2D remission. Application of either form of therapy alone may only have relatively miniscule effects on the aforementioned factors, in relation to the aggregate.

Retinal nerve fiber layer (RNFL) thickness, ganglion cell layer (GCL) thickness, and macular volume (MV) utilizing spectral domain optical coherence tomography (SD-OCT) were compared among patients with Alzheimer's disease (AD) dementia, non-Alzheimer's disease (non-AD) dementia, amnestic mild cognitive impairment (aMCI), Parkinson's disease (PD), and age- and sex-matched controls in a cross-sectional cohort study. A total of 116 participants were diagnosed and evaluated (21 AD, 20 aMCI, 20 non-AD, 20 PD, and 34 controls) after comprehensive neurological, neuropsychology, and magnetic resonance imaging (MRI) volumetric evaluations. Retinal nerve fiber layer thickness, GCL thickness, and MV were measured. Analysis of variance models were used to compare groups on MRI volumetric measures, cognitive test results, and SD-OCT measures. Associations between SD-OCT measures and other measures were performed using mixed-effect models. Spectral domain optical coherence tomography analysis of retinal markers, including RNFL thickness, GCL thickness, and MV, did not differ between amnestic MCI, AD dementia, PD, non-AD, dementia, and age- and sex-matched controls in a well-characterized patient cohort., (© The Author(s) 2016.)

Background: Although existing research highlights the relationship of OSA and cardiovascular disease, the effect of OSA treatment on cardiovascular biomarkers remains unclear. We evaluated the effect of OSA treatment on oxidative stress/inflammation measures., Methods: We conducted a parallel, randomized controlled trial in moderate to severe OSA (apnea-hypopnea index ≥ 15) patients to examine effects of 2-month CPAP vs sham-CPAP on the primary outcome of oxidative stress/inflammation (F2-isoprostanes: ng/mg) and myeloperoxidase: pmol/L) and secondary oxidative stress measures. Exploratory secondary analyses included vascular and systemic inflammation markers. Linear models adjusted for baseline values examined effect of CPAP on biomarker change (least squares means, 95% CI) including secondary stratified analyses examining CPAP adherence and degree of hypoxia., Results: Of 153 participants, 76 were randomized to CPAP and 77 to sham-CPAP. In an intent-to-treat analyses, no significant change was observed in the sham and CPAP groups respectively: F2-isoprostanes (-0.02 [-0.12 to 0.10] vs -0.08 [-0.18 to 0.03]) or myeloperoxidase (-3.33 [-17.02 to 10.37] vs -5.15 [-18.65 to 8.35]), nor other oxidative markers; findings that persisted in analyses stratified by adherence and hypoxia. Exploratory analyses revealed percentage reduction of soluble IL-6 receptor (ng/mL) levels (-0.04 [-0.08 to -0.01] vs 0.02 [-0.02 to 0.06], P = .019) and augmentation index (%) (-6.49 [-9.32 to -3.65] vs 0.44 [-2.22 to 3.10], P < .001) with CPAP compared with sham, respectively., Conclusions: In moderate to severe OSA, 2-month CPAP vs sham did not reduce oxidative stress despite consideration of a broad range of measures, positive airway pressure adherence, and hypoxia burden. These findings suggest that nonoxidative stress pathways primarily modulate OSA-related cardiovascular consequences., Trial Registration: ClinicalTrials.govNCT00607893., (Copyright © 2016 American College of Chest Physicians. All rights reserved.)

Background: Few studies have systematically investigated insomnia in adults with epilepsy., Methods: We performed a prospective cross-sectional investigation of the prevalence, severity, and comorbidities of insomnia in 90 adults with epilepsy using a battery of self-reported instruments and polysomnography. We quantified insomnia severity using the Insomnia Severity Index (ISI)., Results: Fifty-nine of 90 (65.5%) adults with epilepsy reported insomnia (ISI≥8), moderate or severe (ISI≥15) in 28.9%. Good agreement between standard clinical diagnostic criteria and ISI was found for patients with ISI scores <8 and ≥15. Scores on the modified Beck Depression Inventory (mBDI) (r=0.25, p=0.021), the original BDI (r=0.32, p=0.002), and self-reported total sleep duration (TSD) (r=-0.3, p=0.006) were significantly related to ISI score. A multiple regression model found that decreased TSD (ß=-0.93, p=0.007), head trauma (ß=4.37, p=0.003), sedative-hypnotic use (ß=4.86, p=0.002), AED polytherapy (ß=3.52, p=0.005), and asthma/COPD (ß=3.75, p=0.014) were predictors of a higher ISI score. For 63 patients with focal epilepsy, an increased mBDI (ß=0.24, p=0.015), decreased TSD (ß=-1.11, p=0.008), asthma/COPD (ß=4.19, p=0.02), and epilepsy surgery (ß=5.33, p=0.006) were significant predictors of an increased ISI score. Patients with temporal lobe epilepsy (TLE) showed a trend for greater severity compared with those with extra-TLE (ß=-2.92, p=0.054)., Conclusions: Our findings indicate that severity of insomnia in adults with epilepsy is more likely to be associated with comorbid medical and depressive symptoms and less likely to be directly related to epilepsy. Good agreement between standard clinical diagnostic criteria for insomnia and the ISI for subjects without insomnia symptoms and for those with moderate-to-severe symptoms supports the use of this instrument in epilepsy research., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: To determine the feasibility and accuracy of spectral-domain optical coherence tomography (SD-OCT) based grading of anterior chamber cell, using aqueous sampling as a standard, in a rabbit model of anterior uveitis., Methods: Adult Dutch-belted rabbits were preimmunized with M. tuberculosis (Tb) H37RA antigen, 1 week prior to induction of anterior uveitis with an intracameral injection of Tb antigen. The anterior chamber was imaged with SD-OCT, followed by a slit lamp examination. Two independent, trained graders recorded their estimate of anterior chamber cell count using the Standardization of Uveitis Nomenclature (SUN) scores for each eye prior to performing an anterior chamber tap to determine the aqueous cell density using a hemocytometer. Using the aqueous cell density as a standard, correlation with SD-OCT counts were compared to those with SUN scores., Results: Overall, SD-OCT correlated well with the hemocytometer counts (Spearman coefficient = 0.53, P < 0.001) compared with SUN grading and hemocytometer counts (Spearman coefficient = 0.02, P = 0.88). The correlation improved to 0.65 (P < 0.001) when we excluded eyes with corneal thickness ≥ 470 μm. Eyes with corneal thickness ≥ 470 μm exhibited the greatest degree of ocular inflammation and corneal opacity., Conclusions: In our rabbit model, SD-OCT grading of anterior chamber cell correlated significantly better with aqueous cell counts, compared to traditional slit lamp grading. Spectral-domain optical coherence tomography grading of anterior chamber cell may be a good alternative to SUN grading. Although SUN grading remains the clinical gold standard, alternative quantitative methods to assess ocular inflammation could provide insight into disease mechanism and aid in measuring treatment response.

Study Objectives: Data have demonstrated adverse health effects of sleep deprivation. We postulate that oxidative stress and systemic inflammation biomarkers will be elevated in relation to short-term and long-term sleep duration reduction., Methods: We analyzed data from the baseline examination of a randomized controlled trial involving participants with moderate to severe obstructive sleep apnea (OSA). Baseline polysomnography provided the total sleep time (PSG-TST, primary predictor); self-reported habitual sleep duration (SR-HSD) data was collected. Morning measures of oxidative stress and systemic inflammation included: myeloperoxidase (MPO, pmol/L), oxidized low-density lipoprotein (ox-LDL, U/L), F2-isoprostane (ng/mg), paraoxonase 1 (PON1, nmol·min(-1)·mL(-1)), and aryl esterase (μmol·min(-1)·mL(-1)). Linear models adjusted for age, sex, race, body mass index (BMI), cardiovascular disease (CVD), smoking, statin/anti-inflammatory medications, and apnea-hypopnea index were utilized (beta estimates and 95% confidence intervals)., Results: One hundred forty-seven participants comprised the final analytic sample; they were overall middle-aged (51.0 ± 11.7 y), obese (BMI = 37.3 ± 8.1 kg/m(2)), and 17% had CVD. Multivariable models demonstrated a significant inverse association of PSG-TST and MPO (β [95% CI] = -20.28 [-37.48, -3.08], P = 0.021), i.e., 20.3 pmol/L MPO reduction per hour increase PSG-TST. Alternatively, a significant inverse association with ox-LDL and SR-HSD was observed (β [95% CI] = 0.98 [0.96, 0.99], P = 0.027), i.e., 2% ox-LDL reduction per hour increase SR-HSD., Conclusions: Even after consideration of obesity and OSA severity, inverse significant findings were observed such that reduced PSG-TST was associated with elevated MPO levels and SR-HSD with ox-LDL, suggesting differential up-regulation of oxidative stress and pathways of inflammation in acute versus chronic sleep curtailment., Clinical Trial Registration: NIH clinical trials registry number NCT00607893., (© 2016 Associated Professional Sleep Societies, LLC.)

Importance: Vision loss following episcleral brachytherapy for uveal melanoma is difficult to predict for individual patients., Objective: To generate a risk calculator for vision loss following episcleral brachytherapy for uveal melanoma., Design, Setting, and Participants: A retrospective review of data was conducted at a multispecialty tertiary care center in Cleveland, Ohio. All patients with primary ciliary body or choroidal melanoma treated with iodine 125 or ruthenium 106 episcleral brachytherapy between January 1, 2004, and December 30, 2013, were included. Univariate and multivariable Cox proportional hazards were used to determine the influence of baseline patient factors on vision loss. Kaplan-Meier curves (log-rank analyses) were used to estimate freedom from vision loss. Bootstrap resampling was performed to bias correct this estimate., Main Outcomes and Measures: Vision loss (to visual acuity [VA] worse than 20/50 and worse than 20/200)., Results: A total of 311 patients were included in the study, with a mean (SD) age of 62 (14.7) years at start of treatment and a median follow-up of 36 months (interquartile range, 18-60 months). At presentation, VA was better than or equal to 20/50 in 199 patients (64%) and better than or equal to 20/200 in 289 patients (93%). By Kaplan-Meier analysis, VA less than 20/200 at 3 years was not associated with sex, diabetes, systemic hypertension, or hypercholesterolemia but was associated with history of ocular comorbidities, type of isotope (ruthenium 106 or iodine 125), and initial VA ( >20/50 or <20/50). By multivariable analysis, age (hazard ratio [HR], 0.97; 95% CI, 0.94-1.00; P = .06), largest basal diameter (HR, 1.25; 95% CI, 1.16-1.34; P = <.001), total radiation dose to the fovea (HR, 1.03; 95% CI, 1.01-1.04; P = .001) and optic disc (HR, 1.01; 95% CI, 1.00-1.01; P = .005), and initial VA worse than 20/50 (HR, 1.85; 95% CI, 1.20-2.85; P = .005) were predictive of vision loss to a VA of less than 20/200. The concordance index for the full data set was 0.77. Using these data, an online risk calculator was developed to predict vision loss following episcleral brachytherapy., Conclusions and Relevance: The vision prognostication tool presented herein needs to be validated by independent data sets. This tool may improve counseling for patients being evaluated for episcleral brachytherapy. At-risk individuals identified by this tool could be considered for inclusion into trials exploring prevention or treatment of radiation retinopathy and alternative therapies of uveal melanoma.

Context: Recent studies suggest using lower GH cut-points for the glucagon stimulation test (GST) in diagnosing adult GH deficiency (GHD), especially in obese patients. There are limited data on evaluating GH and hypothalamic-pituitary-adrenal (HPA) axes using weight-based dosing for the GST., Objective: To define GH and cortisol cut-points to diagnose adult GHD and secondary adrenal insufficiency (SAI) using the GST, and to compare fixed-dose (FD: 1 or 1.5 mg in patients >90 kg) with weight-based dosing (WB: 0.03 mg/kg). Response to the insulin tolerance test (ITT) was considered the gold standard, using GH and cortisol cut-points of ≥3 ng/ml and ≥18 µg/dL, respectively., Design: 28 Patients with hypothalamic-pituitary disease and 1-2 (n = 14) or ≥3 (n = 14) pituitary hormone deficiencies, and 14 control subjects matched for age, sex, estrogen status and body mass index (BMI) underwent the ITT, FD- and WB-GST in random order., Results: Age, sex ratio and BMI were comparable between the three groups. The best GH cut-point for diagnosis of GHD was 1.0 (92 % sensitivity, 100 % specificity) and 2.0 ng/mL (96 % sensitivity and 100 % specificity) for FD- and WB-GST, respectively. Age negatively correlated with peak GH during FD-GST (r = -0.32, P = 0.04), but not WB-GST. The best cortisol cut-point for diagnosis of SAI was 8.8 µg/dL (92 % sensitivity, 100 % specificity) and 11.2 µg/dL (92 % sensitivity and 100 % specificity) for FD-GST and WB-GST, respectively. Nausea was the most common side effect, and one patient had a seizure during the FD-GST., Conclusion: The GST correctly classified GHD using GH cut-points of 1 ng/ml for FD-GST and 2 ng/ml for WB-GST, hence using 3 ng/ml as the GH cut-point will misclassify some GH-sufficient adults. The GST may also be an acceptable alternative to the ITT for evaluating the HPA axis utilizing cortisol cut-points of 9 µg/dL for FD-GST and 11 µg/dL for WB-GST.

Objective: We evaluated the impact of planned dose reduction and mechanism of action of concomitant AEDs on tolerability in adults with partial-onset seizures undergoing lacosamide (LCM) titration., Methods: Data were collected at baseline and 3-6 and 12-24 months post-LCM initiation. Subjects were categorized as having planned reduction of concomitant AEDs or not; AEDs were categorized as traditional sodium channel blockers (TSCB) or non-TSCB (NTSCB). Groups with/without planned reduction were compared on the presence and number of treatment-emergent adverse events (TEAEs) using chi-square tests or logistic regression and on time to LCM discontinuation with time-to-event methods controlling for standardized (STD) AED dose, a measure of concomitant AED load. Similar analyses were performed comparing subjects taking TSCB and NTSCB agents and used to identify relationships with ≥50% decreases in seizure frequency., Results: One hundred six adults (mean age 41.4 ± 13.4; 50% male) underwent LCM titration from June 2009-2011 with complete data. Reduction of concomitant AEDs was planned at the time of LCM initiation in 59 (55.7%) subjects. Fewer subjects with planned reduction had TEAEs (49.2% vs. 68.1%; p=0.05), and these subjects had a lower risk of TEAEs (OR 0.36; p=0.019) after adjusting for STD AED dose. The hazard ratio (95% CI) for LCM discontinuation was 0.46 (0.23, 0.94) in subjects with planned reduction of concomitant AEDs vs. others (p=0.033) and 3.29 (1.01, 10.70) in subjects taking TSCB vs. NTSCB agents (p=0.048). Among all cases, those who ever had TEAEs had significantly higher STD dose at both follow-up visits (p=0.033 and p=0.023, respectively). Seizure outcomes were not significantly different between groups at the last follow-up assessment., Significance: Planned reduction of concomitant AEDs during LCM initiation and the use of NTSCB agents only are associated with a reduced risk of TEAEs and LCM discontinuation in adults with partial-onset seizures. This study extends prior observations by considering total AED load in the assessment of tolerability and supports the benefits of early reduction of concomitant AEDs during LCM initiation., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Grasses are ancestrally tropical understory species whose current dominance in warm open habitats is linked to the evolution of C4 photosynthesis. C4 grasses maintain high rates of photosynthesis in warm and water stressed environments, and the syndrome is considered to induce niche shifts into these habitats while adaptation to cold ones may be compromised. Global biogeographic analyses of C4 grasses have, however, concentrated on diversity patterns, while paying little attention to distributional limits. Using phylogenetic contrast analyses, we compared macro-climatic distribution limits among ~1300 grasses from the subfamily Panicoideae, which includes 4/5 of the known photosynthetic transitions in grasses. We explored whether evolution of C4 photosynthesis correlates with niche expansions, niche changes, or stasis at subfamily level and within the two tribes Paniceae and Paspaleae. We compared the climatic extremes of growing season temperatures, aridity, and mean temperatures of the coldest months. We found support for all the known biogeographic distribution patterns of C4 species, these patterns were, however, formed both by niche expansion and niche changes. The only ubiquitous response to a change in the photosynthetic pathway within Panicoideae was a niche expansion of the C4 species into regions with higher growing season temperatures, but without a withdrawal from the inherited climate niche. Other patterns varied among the tribes, as macro-climatic niche evolution in the American tribe Paspaleae differed from the pattern supported in the globally distributed tribe Paniceae and at family level.

Importance: There is a lack of information regarding the role of systemic surveillance in patients with primary uveal melanoma., Objective: To evaluate the utility of serial hepatic ultrasonography (USG) for detection of asymptomatic liver metastases in patients undergoing surveillance after primary treatment of uveal melanoma., Design, Setting, and Participants: Retrospective cohort study reviewing data from patients with primary uveal melanoma treated between October 2003 and October 2012 at a multispecialty tertiary care center. Patients were managed using a standardized protocol. Initial staging was done with contrast-enhanced computed tomography of the chest, abdomen, and pelvis. This was followed by periodic surveillance with hepatic USG and liver function tests scheduled every 6 months for the first 5 years and annually thereafter. Abnormal surveillance hepatic USG findings were categorized as (1) cyst or hemangioma, (2) indeterminate lesion, (3) suspicious for metastasis, or (4) consistent with metastasis. If indicated, hepatic USG abnormalities were confirmed by additional imaging modalities (confirmatory scans) such as computed tomography or magnetic resonance imaging. Liver biopsy was performed only if the confirmatory scan was positive., Main Outcomes and Measures: Sensitivity, specificity, and positive predictive value of hepatic USG for detecting asymptomatic liver metastases., Results: In 263 patients (121 men, 142 women; mean [SD] age at diagnosis, 61.1 [13.9] years), a total of 1390 hepatic USGs were performed, with a mean of 5.3 per patient (range, 1-17 per patient). Overall, 86 hepatic USGs of 71 patients (27%) were reported as abnormal. Of the 13 lesions identified as a cyst/hemangioma and 17 as indeterminate, 1 was found to be metastatic in each group (8% and 6%, respectively). Of 36 patients with findings suspicious for metastasis, 23 (64%) had metastasis confirmed. All 5 patients (100%) with findings consistent with metastasis had biopsy-proven metastasis. The sensitivity, specificity, and positive predictive value of hepatic USG for findings that were indeterminate or suspicious for metastasis were 96% (95% CI, 80%-99%), 88% (95% CI, 83%-91%), and 45% (95% CI, 33%-59%), respectively. Specificity of the confirmatory scan was greater than that of hepatic USG (93% [95% CI, 89%-96%] vs 88% [95% CI, 83%-91%], respectively; P < .001). Only 4 of 30 patients (13%) with metastasis had abnormal findings on simultaneous liver function tests., Conclusions and Relevance: A stepwise surveillance protocol based on serial hepatic USGs followed by confirmatory scans offers high likelihood of detecting asymptomatic metastases in patients with primary uveal melanoma.

Background: We assessed the impact of retinoid X receptor (RXR) agonist bexarotene on brain amyloid measured by amyloid imaging in patients with Alzheimer's disease (AD) in a proof-of-concept trial., Methods: Twenty patients with AD [Mini Mental State Examination (MMSE) score 10-20 inclusive] with positive florbetapir scans were randomized to receive 300 mg of bexarotene or placebo for 4 weeks. The amyloid imaging result was the primary outcome. Whole-population analyses and prespecified analyses by genotype [apolipoprotein E ε4 (ApoE4) carriers and ApoE4 noncarriers] were conducted. Secondary outcomes included scores on the Alzheimer's Disease Assessment Scale-Cognitive subscale, Alzheimer's Disease Cooperative Study-Activities of Daily Living scale, MMSE, Clinical Dementia Rating scale, and Neuropsychiatric Inventory. Serum amyloid-β (Aβ) peptide sequences Aβ1-40 and Aβ1-42 measurements were collected as biomarker outcomes., Results: There was no change in the composite or regional amyloid burden when all patients were included in the analysis. ApoE4 noncarriers showed a significant reduction in brain amyloid on the composite measure in five of six regional measurements. No change in amyloid burden was observed in ApoE4 carriers. There was a significant association between increased serum Aβ1-42 and reductions in brain amyloid in ApoE4 noncarriers (not in carriers). There were significant elevations in serum triglycerides in bexarotene-treated patients. There was no consistent change in any clinical measure., Conclusions: The primary outcome of this trial was negative. The data suggest that bexarotene reduced brain amyloid and increased serum Aβ1-42 in ApoE4 noncarriers. Elevated triglycerides could represent a cardiovascular risk, and bexarotene should not be administered outside a research setting. RXR agonists warrant further investigations as AD therapies., Trial Registration: ClinicalTrials.gov identifier NCT01782742 . Registered 29 January 2013.

Background: Median arcuate ligament syndrome (MALS) is a rare disorder characterized by postprandial abdominal pain, weight loss, and celiac stenosis. Diagnosis can be challenging, leading to a delay in treatment. We report on our continued experience using a laparoscopic approach for this uncommon diagnosis., Methods: This is an Institutional Review Board-approved, prospectively collected retrospective analysis of patients treated with laparoscopic MAL release at our institution. Data collected included patient demographics, preoperative symptoms, operative approach, and postoperative outcomes. Patients were then contacted to complete a postoperative survey designed to assess the improvement of symptoms and overall patient satisfaction., Results: A total of 39 patients (33 women and 6 men) underwent laparoscopic MAL release from March 2007 to July 2014. Mean age was 40.6 years (range, 17-77 years). Thirty of 39 patients had a postoperative celiac axis ultrasound. Twenty-three had a patent celiac axis on postoperative duplex. Of the remaining 7, 5 with residual celiac axis stenosis and 1 with occlusion, reported complete resolution of their symptoms. One remaining patient with occlusion remained symptomatic. Thirty-three of 39 (84.6%) reported symptom relief after surgery. Nine of 33 (27.3%) responders had cardiovascular risk factors versus 4 of 6 (67%) nonresponders. Five patients with atypical presentations underwent preoperative diagnostic celiac plexus block using local anesthetic, with 4 reporting symptom reliefs after block. These 4 patients also reported postoperative symptom relief. One patient of 39 received a postoperative celiac stent placement and remained symptomatic. There were 4 conversions to open surgery (10.3%) and no deaths., Conclusions: Laparoscopic MAL release continues to be a safe and effective means of managing MALS. Our data suggest that the symptoms associated with MALS are not related to vascular compromise, and atherosclerotic risk factors may predict poorer outcomes. Symptomatic relief is seen in the vast majority of patients undergoing this procedure. However, patient selection remains critically important in obtaining optimal results., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Importance: To our knowledge, longitudinal assessment of depression, anxiety, and decision regret (a sense of disappointment or dissatisfaction in the decision) in patients undergoing prognostication for uveal melanoma does not exist., Objective: To report on depression, anxiety, and decision regret before and after testing to estimate uveal melanoma prognosis., Design, Setting, and Participants: Prospective interventional case series conducted at an institutional referral practice of 96 patients with clinical diagnosis of uveal melanoma who underwent prognostication at the time of primary therapy., Main Outcomes and Measures: Depression, anxiety, and decision regret prior to prognostication (baseline) and at 3 and 12 months afterwards. The Hospital Anxiety and Depression Scale (HADS) and Decision Regret Scale were self-administered by the patients prior to prognostication (baseline) and at 3 and 12 months afterwards. Data were summarized using means and standard deviations for continuous measures, frequencies, and percentages for categorical factors. A mixed model was used to assess the trajectory of HADS anxiety and the associations between HADS anxiety and baseline HADS depression, baseline decision regret, prognostication test result, and adjuvant therapy, respectively, while adjusting for age and sex., Results: Ninety-six patients (median age 60.7 years) completed baseline questionnaires. The mean (SD) HADS anxiety score at baseline (7.4 [4.0]) was higher than at 3 months (5.4 [3.7]; P < .001) or 12 months (4.7 [3.4]; P < .001), and decreased with older age (coefficient estimate [SD], -0.06 [0.02]; P < .001). The decision regret score was associated with baseline HADS depression score (coefficient estimate [SE], -1.17 [0.43]; P < .007), and HADS depression score increased with baseline HADS anxiety score (coefficient estimate [SE], 0.39 [0.06]; P < .001)., Conclusions and Relevance: Our study raises questions about decision regret in patients who agree to have a prognostic test that may not help guide treatment. Although decision regret appears to lessen or dissipate with time, study on larger numbers of patients is necessary to elucidate factors that may be addressed to mitigate decision regret.

Study Objective: We examined the prevalence of obstructive sleep apnea (OSA) among patients undergoing cardiac surgery and its impact on postoperative outcomes., Methods: Subjects were recruited from inpatient cardiovascular surgery units at two tertiary care centers. Crystal Monitor 20-H recorded polysomnograms preoperatively. Regression analyses were performed to explore associations between OSA using different apnea-hypopnea index (AHI) cutoffs and postoperative outcomes adjusting for key covariates. Prevalence of postoperative outcomes was compared among groups defined by AHI and left ventricle ejection fraction (LVEF) median cutoffs., Results: Of 107 participants, the AHI was ≥ 5 in 79 (73.8%), ≥ 10 in 63 (58.9%), ≥ 15 in 51(47.7%), and ≥ 30 in 29 (27.1%). Patients with AHI ≥ 15 had significantly lower LVEF (p < 0.001). Logistic regression analyses with OSA cutoffs as above adjusting for age, gender, race, BMI, and LVEF found no significant increase in odds for any postoperative outcomes. No significant differences were found in %Total sleep time (TST) with SpO2 < 90% between AHI or LVEF groups, or by presence/absence of complications. Patients with any amount of TST with SpO2 < 90% had greater BMI, longer OR tube time, and greater prevalence of prolonged intubation (p = 0.007, 0.035, 0.038, respectively)., Conclusions: OSA is highly prevalent in patients undergoing cardiovascular surgery. It could not be shown that OSA was significantly associated with adverse postoperative outcomes, but this may have been due to an insufficient number of subjects. AHI ≥ 15 was associated with lower LVEF. Larger samples are required to explore the impact of OSA on key postoperative outcomes that have clinical and economic importance in the care of cardiovascular surgery populations., Commentary: A commentary on this article appears in this issue on page 1081., (© 2015 American Academy of Sleep Medicine.)

Objective: Expert opinion and a consensus statement on Cushing syndrome (CS) indicate that in a patient with a clinical presentation and biochemical studies consistent with a pituitary etiology, the presence of a pituitary tumor ≥6 mm is highly suggestive of Cushing disease (CD). The purpose of the present study was to determine the optimal pituitary tumor size that can differentiate between patients with CD and ectopic adrenocorticotrophic hormone (ACTH) secretion (EAS) and obviate the need for inferior petrosal sinus sampling (IPSS)., Methods: We performed a retrospective study of 130 patients seen between 2000 and 2012 including 104 patients with CD and 26 patients with EAS., Results: A pituitary lesion was reported in 6/26 (23%) patients with EAS and 71/104 (68.3%) patients with CD, with median (range) sizes of 5 mm (3-14) and 8 mm (2-31), respectively. All tumors in the EAS group measured ≤6 mm except for 1 that measured 14 mm. The presence of a pituitary tumor >6 mm in size had 40% sensitivity and 96% specificity for the diagnosis of CD. ACTH levels >209 pg/mL and serum potassium <2.7 mmol/L were found in patients with EAS. All patients with EAS had a 24-hour urine free cortisol (UFC) >3.4 times the upper limit of normal (×ULN) Conclusion: Pituitary incidentalomas as large as 14 mm in size can be seen in patients with EAS. However, the 6-mm tumor size cut-off value provided 96% specificity and may be a reasonable threshold to proceed with surgery without the need for IPSS when the biochemical data support a pituitary etiology.