Dural infolding during C1-2 myelography

Inward buckling of the dura at C1-2 may occasionally occur with hyperextension of the neck and can result in a difficult or unsuccessful puncture when the posterior lateral C1-2 approach is used for cervical myelography. In this circumstance, placement of the head in a neutral or slightly flexed position may widen the posterior subarachnoid space and facilitate the needle puncture.     

The association of PTSD with physical and mental health functioning and disability (VA Cooperative Study #569: the course and consequences of posttraumatic stress disorder in Vietnam-era Veteran twins)

Purpose

To assess the relationship of posttraumatic stress disorder (PTSD) with health functioning and disability in Vietnam-era Veterans.

Methods

A cross-sectional study of functioning and disability in male Vietnam-era Veteran twins. PTSD was measured by the Composite International Diagnostic Interview; health functioning and disability were assessed using the Veterans RAND 36-Item Health Survey (VR-36) and the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0). All data collection took place between 2010 and 2012.

Results

Average age of the 5,574 participating Veterans (2,102 Vietnam theater and 3,472 non-theater) was 61.0 years. Veterans with PTSD had poorer health functioning across all domains of VR-36 and increased disability for all subscales of WHODAS 2.0 (all p < .001) compared with Veterans without PTSD. Veterans with PTSD were in poorer overall health on the VR-36 physical composite summary (PCS) (effect size = 0.31 in theater and 0.47 in non-theater Veterans; p < .001 for both) and mental composite summary (MCS) (effect size = 0.99 in theater and 0.78 in non-theater Veterans; p < .001 for both) and had increased disability on the WHODAS 2.0 summary score (effect size = 1.02 in theater and 0.96 in non-theater Veterans; p < .001 for both). Combat exposure, independent of PTSD status, was associated with lower PCS and MCS scores and increased disability (all p < .05, for trend). Within-pair analyses in twins discordant for PTSD produced consistent findings.

Conclusions

Vietnam-era Veterans with PTSD have diminished functioning and increased disability. The poor functional status of aging combat-exposed Veterans is of particular concern.     

Modulation of gastrointestinal function by MuDelta,a mixed μ opioid receptor agonist/ μ opioid receptor antagonist

BACKGROUND & PURPOSE

Loperamide is a selective µ opioid receptor agonist acting locally in the gastrointestinal (GI) tract as an effective anti-diarrhoeal but can cause constipation. We tested whether modulating µ opioid receptor agonism with δ opioid receptor antagonism, by combining reference compounds or using a novel compound (‘MuDelta’), could normalize GI motility without constipation.

EXPERIMENTAL APPROACH

MuDelta was characterized in vitro as a potent µ opioid receptor agonist and high-affinity δ opioid receptor antagonist. Reference compounds, MuDelta and loperamide were assessed in the following ex vivo and in vivo experiments: guinea pig intestinal smooth muscle contractility, mouse intestinal epithelial ion transport and upper GI tract transit, entire GI transit or faecal output in novel environment stressed mice, or four weeks after intracolonic mustard oil (post-inflammatory). Colonic δ opioid receptor immunoreactivity was quantified.

KEY RESULTS

δ Opioid receptor antagonism opposed µ opioid receptor agonist inhibition of intestinal contractility and motility. MuDelta reduced intestinal contractility and inhibited neurogenically-mediated secretion. Very low plasma levels of MuDelta were detected after oral administration. Stress up-regulated δ opioid receptor expression in colonic epithelial cells. In stressed mice, MuDelta normalized GI transit and faecal output to control levels over a wide dose range, whereas loperamide had a narrow dose range. MuDelta and loperamide reduced upper GI transit in the post-inflammatory model.

CONCLUSIONS AND IMPLICATIONS

MuDelta normalizes, but does not prevent, perturbed GI transit over a wide dose-range in mice. These data support the subsequent assessment of MuDelta in a clinical phase II trial in patients with diarrhoea-predominant irritable bowel syndrome.     

Pharmacokinetics and pharmacodynamics of nifedipine infusion in normal volunteers.

Two studies of the pharmacokinetics and pharmacodynamics of intravenous nifedipine infusion were performed: the first, a randomised double-blind crossover study of nifedipine and its vehicle in eight subjects, the second a dose ranging study in nine subjects. Nifedipine pharmacokinetics did not vary with dose or duration of infusion up to 8 h, and are similar to those reported for other nifedipine preparations. Nifedipine increased heart rate and forearm blood flow and decreased blood pressure after bolus injection but not during prolonged infusion. The vehicle decreased blood pressure and increased forearm blood flow after bolus injection but not during prolonged infusion. It did not affect heart rate. The vehicle's haemodynamic activity has not been previously recognised and is of potential importance in the study of this and similar preparations of calcium antagonists.     

<Emphasis Type="Italic">Celebremos La Salud</Emphasis>: A Community-Based Intervention for Hispanic and Non-Hispanic White Women Living in a Rural Area

The evaluation for Celebremos La Salud, a community randomized trial of Hispanic cancer prevention found no differences in mammography screening rates between intervention and control communities. The goal of the present study was to determine reasons for the intervention's lack of effectiveness. In the first aim, we assessed reach of the intervention. In the second, we assessed which intervention activities were associated with mammography use. In the third, we examined whether factors related to health care access, education level, or age modified the effect of the intervention. Data were used from a post-intervention survey of 20 rural communities in Washington State. Hispanic (N = 202) and non-Hispanic White (N = 389) women, over age 40 formed the sample. Reporting having awareness of or having participated in intervention activities was positively associated with Hispanic ethnicity and intervention group and negatively associated with lack of health insurance and having a lower education level. Only one intervention activity was associated with screening use. Having participated in presentations at organizations was positively associated with having had a mammogram in the previous 2 years for Hispanic women. No individual level modifiers influenced the intervention's effectiveness. Heavily targeting the intervention to Hispanic women and not reaching as many White women may have contributed to the lack of intervention effect. Increasing mammography screening rates among women living in a rural area may require improved access to health care and reaching women with lower education levels and lack of health insurance.     

Development and implementation of a lifestyle intervention to promote physical activity and healthy diet in the Dutch general practice setting: the BeweegKuur programme

Background  

The number of patients with diabetes is increasing. BeweegKuur (Dutch for 'Exercise Therapy') is a Dutch lifestyle intervention which aims to effectively and feasibly promote physical activity and better dietary behaviour in primary health care to prevent diabetes.     

Likelihood‐based analysis of outcome‐dependent sampling designs with longitudinal data

The use of outcome‐dependent sampling with longitudinal data analysis has previously been shown to improve efficiency in the estimation of regression parameters. The motivating scenario is when outcome data exist for all cohort members but key exposure variables will be gathered only on a subset. Inference with outcome‐dependent sampling designs that also incorporates incomplete information from those individuals who did not have their exposure ascertained has been investigated for univariate but not longitudinal outcomes. Therefore, with a continuous longitudinal outcome, we explore the relative contributions of various sources of information toward the estimation of key regression parameters using a likelihood framework. We evaluate the efficiency gains that alternative estimators might offer over random sampling, and we offer insight into their relative merits in select practical scenarios. Finally, we illustrate the potential impact of design and analysis choices using data from the Cystic Fibrosis Foundation Patient Registry.     

Higher order aberrations,refractive error development and myopia control: a review

Evidence from animal and human studies suggests that ocular growth is influenced by visual experience. Reduced retinal image quality and imposed optical defocus result in predictable changes in axial eye growth. Higher order aberrations are optical imperfections of the eye that alter retinal image quality despite optimal correction of spherical defocus and astigmatism. Since higher order aberrations reduce retinal image quality and produce variations in optical vergence across the entrance pupil of the eye, they may provide optical signals that contribute to the regulation and modulation of eye growth and refractive error development. The magnitude and type of higher order aberrations vary with age, refractive error, and during near work and accommodation. Furthermore, distinctive changes in higher order aberrations occur with various myopia control treatments, including atropine, near addition spectacle lenses, orthokeratology and soft multifocal and dual-focus contact lenses. Several plausible mechanisms have been proposed by which higher order aberrations may influence axial eye growth, the development of refractive error, and the treatment effect of myopia control interventions. Future studies of higher order aberrations, particularly during childhood, accommodation, and treatment with myopia control interventions are required to further our understanding of their potential role in refractive error development and eye growth.     

Radiological assessment of dysphagia with endoscopic correlation

Four hundred fifty consecutive patients with dysphagia were evaluated radiologically over a 14-month period; 127 of these (28.2%) were also examined endoscopically. The most common abnormality seen was dysmotility (34%), followed by hiatal hernia, benign stricture, and esophagitis. Correlation with endoscopy was generally good. Radiologic study demonstrated all cases of esophageal malignancy; radiologic/endoscopic correlation was also strong in patients with moderate or severe esophagitis, though the radiologist had some difficulty detecting mild inflammation. Endoscopy failed to demonstrate some benign strictures. Radiologic study was relatively accurate in detecting significant organic disease; most motility disorders were not detected by endoscopy. For these reasons, as well as lower cost, increased convenience, and patient comfort, radiologic assessment is recommended as the primary method of evaluating patients with dysphagia.     

An evaluation of constrained randomization for the design and analysis of group‐randomized trials

In group‐randomized trials, a frequent practical limitation to adopting rigorous research designs is that only a small number of groups may be available, and therefore, simple randomization cannot be relied upon to balance key group‐level prognostic factors across the comparison arms. Constrained randomization is an allocation technique proposed for ensuring balance and can be used together with a permutation test for randomization‐based inference. However, several statistical issues have not been thoroughly studied when constrained randomization is considered. Therefore, we used simulations to evaluate key issues including the following: the impact of the choice of the candidate set size and the balance metric used to guide randomization; the choice of adjusted versus unadjusted analysis; and the use of model‐based versus randomization‐based tests. We conducted a simulation study to compare the type I error and power of the F‐test and the permutation test in the presence of group‐level potential confounders. Our results indicate that the adjusted F‐test and the permutation test perform similarly and slightly better for constrained randomization relative to simple randomization in terms of power, and the candidate set size does not substantially affect their power. Under constrained randomization, however, the unadjusted F‐test is conservative, while the unadjusted permutation test carries the desired type I error rate as long as the candidate set size is not too small; the unadjusted permutation test is consistently more powerful than the unadjusted F‐test and gains power as candidate set size changes. Finally, we caution against the inappropriate specification of permutation distribution under constrained randomization. An ongoing group‐randomized trial is used as an illustrative example for the constrained randomization design. Copyright © 2015 John Wiley & Sons, Ltd.