Adjuvant chemotherapy for stage III colon cancer: Relative dose intensity and survival among veterans

Background: Given the paucity of information on dose intensity, the objective of this study is to describe the use of adjuvant chemotherapy for stage III colon cancer, focusing on relative dose intensity (RDI), overall survival (OS) and disease-free survival (DFS). Methods: Retrospective cohort of 367 patients diagnosed with stage III colon cancer in 2003-2008 and treated at 19 VA medical centers. Kaplan-Meier curves summarize 5-year OS and 3-year DFS by chemotherapy regimen and RDI, and multivariable Cox proportional hazards regression was used to model these associations. Results: 5-fluorouracil/leucovorin (FU/LV) was the most commonly initiated regimen in 2003 (94.4%) and 2004 (62.7%); in 2005-2008, a majority of patients (60%-74%) was started on an oxaliplatin-based regimen. Median RDI was 82.3%. Receipt of >70% RDI was associated with better 5-year OS (p70% RDI at the first year (HR=0.58; 95% CI=0.37-0.89) and married status (HR=0.66; 95% CI=0.45-0.97) were associated with significantly decreased risk of death, while age ≥75 (versus 55-64) (HR=2.06; 95% CI=1.25-3.40), Charlson Comorbidity Index (HR=1.17; 95% CI=1.06-1.30), T4 tumor status (versus T1/T2) (HR=5.88; 95% CI=2.69-12.9), N2 node status (HR=1.68; 95% CI=1.12-2.50) and bowel obstruction (HR=2.32, 95% CI=1.36-3.95) were associated with significantly increased risk. Similar associations were observed for DFS. Conclusion: Patients with stage III colon cancer who received >70% RDI had improved 5-year OS. The association between RDI and survival needs to be examined in studies of adjuvant chemotherapy for colon cancer outside of the VA

A Multisite Preregistered Paradigmatic Test of the Ego-Depletion Effect

We conducted a preregistered multilaboratory project (k = 36; N = 3,531) to assess the size and robustness of ego-depletion effects using a novel replication method, termed the paradigmatic replication approach. Each laboratory implemented one of two procedures that was intended to manipulate self-control and tested performance on a subsequent measure of self-control. Confirmatory tests found a nonsignificant result (d = 0.06). Confirmatory Bayesian meta-analyses using an informed-prior hypothesis (δ = 0.30, SD = 0.15) found that the data were 4 times more likely under the null than the alternative hypothesis. Hence, preregistered analyses did not find evidence for a depletion effect. Exploratory analyses on the full sample (i.e., ignoring exclusion criteria) found a statistically significant effect (d = 0.08); Bayesian analyses showed that the data were about equally likely under the null and informed-prior hypotheses. Exploratory moderator tests suggested that the depletion effect was larger for participants who reported more fatigue but was not moderated by trait self-control, willpower beliefs, or action orientation.</p

A comparison of four methods of tonometry: method agreement and interobserver variability

Aim: To compare the inter-method agreement in intraocular pressure (IOP) measurements made with four different tonometric methods. Methods: IOP was measured with the Goldmann applanation tonometer (GAT), Tono-Pen XL, ocular blood flow tonograph (OBF), and Canon TX-10 non-contact tonometer (NCT) in a randomised order in one eye of each of 105 patients with ocular hypertension or glaucoma. Three measurements were made with each method, and by each of two independent GAT observers. GAT interobserver and tonometer inter-method agreement was assessed by the Bland-Altman method. The outcome measures were 95% limits of agreement for IOP measurements between GAT observers and between tonometric methods, and 95% confidence intervals for intra-session repeated measurements. Results: The mean differences (bias) in IOP measurements were 0.4 mm Hg between GAT observers, and 0.6 mm Hg, 0.1 mm Hg, and 0.7 mm Hg between GAT and Tono-Pen, OBF, and NCT, respectively. The 95% limits of agreement were smallest (bias ±2.6 mm Hg) between GAT observers, and larger for agreement between the GAT and the Tono-Pen, OBF, and NCT (bias ±6.7, ±5.5, and ±4.8 mm Hg, respectively). The OBF and NCT significantly underestimated GAT measurements at lower IOP and overestimated these at higher IOP. The repeatability coefficients for intra-session repeated measurement for each method were ±2.2 mm Hg and ±2.5 mm Hg for the GAT, ±4.3 mm Hg for the Tono-Pen, ±3.7 mm Hg for the OBF, and ±3.2 mm Hg for the NCT. Conclusions: There was good interobserver agreement with the GAT and moderate agreement between the NCT and GAT. The differences between the GAT and OBF and between the GAT and Tono-Pen probably preclude the OBF and Tono-Pen from routine clinical use as objective methods to measure IOP in normal adult eyes

Impact of Behavioral Insomnia Treatments on Quality of Life in Post-menopausal Women

Introduction: Insomnia in post-menopausal women is commonly associated with reduced quality of life. Preliminary data suggest that both Cognitive Behavioral Therapy for Insomnia (CBT-I) and the Sleep Restriction Therapy component of CBTI (SRT) reduce insomnia severity in this population. While SRT is the shorter alternative to full CBTI in improving insomnia (2 versus 6 weeks), the differences in impact on quality of life in this population have not yet been investigated. Methods: 148 females (mean age=56.5, SD=5.61) with insomnia concurrent with menopause were randomized to one of three conditions: CBT-I (N=50), SRT (N=49), and Information-only Control (IC, N=49). Quality of life was measured using the Short Form Health Survey (SF-36; range=0-100), administered at baseline, immediately post-treatment, and at 6-month follow-up. Results: Repeated-measures ANOVA revealed that the CBT-I, SRT, and IC did not differ at baseline on any domains (p\u3e;.05) except for emotional role-limitations (

The influence of central corneal thickness and age on intraocular pressure measured by pneumotonometry, non-contact tonometry, the Tono-Pen XL, and Goldmann applanation tonometry

Aims: To evaluate the influence of central corneal thickness (CCT) on intraocular pressure (IOP) measurements made with the Goldmann applanation tonometer (GAT), Tono-Pen XL, ocular blood flow tonograph (OBF), and Canon TX-10 non-contact tonometer (NCT). Methods: CCT was recorded for either eye (randomly selected) of each of 105 untreated patients with ocular hypertension and glaucoma attending the glaucoma research unit at Moorfields Eye Hospital. For each of the selected eyes, IOP was measured with the GAT (two observers), Tono-Pen, OBF, and NCT in a randomised order. The relation of measured IOP and of inter-tonometer differences with CCT and subject age was explored by linear regression analysis. Results: A significant association between measured IOP and CCT was found with each instrument. The change in measured IOP for a 10 μm increase in CCT was 0.28, 0.31, 0.38, and 0.46 for the GAT, Tono-Pen, OBF, and NCT, respectively (all p⩽0.05). There was a significant association between the NCT/GAT differences and CCT, with a tendency of NCT to overestimate GAT in eyes with thicker corneas. There was a significant association between GAT/Tono-Pen and OBF/Tono-Pen differences and age, with a tendency of GAT and OBF to overestimate the Tono-Pen in eyes of older subjects. Conclusion: IOP measurement by all four methods is affected by CCT. The NCT is affected by CCT significantly more than the GAT. Subject age has a differential effect on the IOP measurements made by the GAT and OBF compared to the Tono-Pen

Arousability of insomnia patients is not impacted by the orexin antagonist suvorexant (10 mg and 20 mg)

Introduction: Ability to awaken to external or internal stimuli (arousability) has significant clinical implications in patients with a variety of medical disorders (e.g., sleep related breathing disorders, GERD) and life circumstances (e.g. caregiver responsibility, environmental threat). Arousability with an orexin antagonist has been demonstrated in an animal model. Yet, arousability has not been assessed with orexin antagonists in humans. Thus, we evaluated Auditory Awakening Threshold (AAT) with suvorexant in comparison to placebo. Methods: In a placebo-controlled double-blind 3-way crossover study in 12 (7F) subjects with insomnia, AAT to 1000 Hz tones ∼2-hrs after bedtime was determined following suvorexant 10 and 20 mg (SUV10, 20) compared to placebo (PBO) administered 30 minutes before bedtime. Tones were presented during stable (5 consecutive minutes) stage 2 sleep in 5db increments starting at 30db. The AAT was compared using one-way repeated measures analysis of variance. Standard sleep parameters of latency to persistent sleep (LPS), wake after sleep onset (WASO), and total sleep time (TST) were also assessed for each condition using paired comparisons. Results: Neither the AAT (expressed as dB) for SUV10 (74.18 ± 23.46) nor SUV20 (83.76 ± 20.24) was significantly different from PBO (79.18 ± 22.34; p = .34). SUV was an active dose in these subjects as seen by significantly greater total sleep time following SUV20 (446.35 ± 23.94 minutes; p = 0.024) compared to placebo (401.09 ± 51.29 minutes). In addition, decreased WASO was observed following SUV20 (22.85 ± 18.50 minutes; p = 0.024) compared to placebo (55.69 ± 40.00 minutes). No significant differences were found for effects of condition on LPS likely reflecting the small sample size. Conclusion: The orexin antagonist suvorexant improved sleep without decreasing nocturnal arousabilty. These results are in contrast to published reports demonstrating blunting of arousal response with benzodiazepine receptor agonists (e.g., zolpidem). Future studies should investigate whether differential arousal response extends into the post-arousal period thereby impacting other behaviors such as ambulating, memory, and cognitive function

The effect of orbital decompression surgery on refraction and intraocular pressure in patients with thyroid orbitopathy

Purpose: To investigate the effect of orbital decompression surgery in thyroid orbitopathy (TO) on both refractive status and intraocular pressure (IOP). Patients and methods: A prospective, multicentre, consecutive audit of patients undergoing thyroid decompression surgery. Indications for surgery included cosmetically unacceptable proptosis or corneal exposure. Exclusion criteria included the following: previous orbital surgery, glaucoma, corneal disease, steroid use in the preceding 12 months, or an acute optic neuropathy. Automated refraction, keratometry, pachymetry, Hertel exophthalmometry, and IOP were recorded at 1 month pre- and 3 months postoperatively. IOP using the Tono-Pen (mean of three readings) was measured in the primary, upgaze, and downgaze positions. Results: Data were collected from 52 orbits of 33 patients (East Grinstead, New York, and Adelaide). There was no significant difference between pre- and postoperative data for sphere, cylinder, or central corneal thickness (CCT). The mean spherical equivalent was −0.43±1.49 D pre-operatively and −0.28±1.52 D postoperatively. The steepest meridian of corneal curvature was 93.1 degrees pre- and 94.2 degrees postoperatively, with no significant difference. Mean IOP significantly decreased when measuring by Goldmann applanation tonometry (GAT) (2.28 mm Hg, * P=0.001) and Tono-Pen (3.06 mm Hg, * P=<0.0001). IOP measured in upgaze was significantly greater than that in the primary position. Regression analysis between change in IOP and either Hertel exophthalmometry or the number of orbital walls decompressed was non-significant (*Student's t-test). Conclusion: Patients with TO undergoing orbital decompression had, on average, with-the-rule astigmatism not affected by orbital decompression surgery. IOP was significantly reduced by decompression surgery although no relationship between IOP and the degree of decompression was observed.JH Norris, JJ Ross, M Kazim, D Selva, and R Malhotr