Electrical impedance myography as a biomarker to assess ALS progression

Abstract Electrical impedance myography (EIM), a non-invasive, electrophysiological technique, has preliminarily shown value as an ALS biomarker. Here we perform a multicenter study to further assess EIM's potential for tracking ALS. ALS patients were enrolled across eight sites. Each subject underwent EIM, handheld dynamometry (HHD), and the ALS Functional Rating Scale-revised (ALSFRS-R) regularly. Techniques were compared by assessing the coefficient of variation (CoV) in the rate of decline and each technique's correlation to survival. Results showed that in the 60 patients followed for one year, EIM phase measured from the most rapidly progressing muscle in each patient had a CoV in the rate of decline of 0.62, compared to HHD (0.82) and the ALSFRS-R (0.74). Restricting the measurements to the first six months gave a CoV of 0.55 for EIM, 0.93 for HHD, and 0.84 for ALSFRS-R. For both time-periods, all three measures correlated with survival. Based on these data, a six-month clinical trial designed to detect a 20% treatment effect with 80% power using EIM would require only 95 patients/arm compared to the ALSFRS-R, which would require 220 subjects/arm. In conclusion, EIM can serve as a useful ALS biomarker that offers the prospect of greatly accelerating phase 2 clinical trials.     

Exercise for Improving Age-Related Hyperkyphotic Posture: A Systematic Review

Objective

To evaluate previous research to determine if exercise can improve preexisting hyperkyphosis by decreasing the angle of thoracic kyphosis in adults aged ≥45 years.

Data Sources

PubMed, Embase, and the Cumulative Index to Nursing and Allied Health Literature databases were searched for studies related to posture, exercise, and age ≥45 years. Online conference proceedings of the American Society for Bone and Mineral Research, American Physical Therapy Association, and Gerontological Society of America were also searched.

Study Selection

Two independent reviewers screened the titles and abstracts and selected studies that tested the effect of exercise on measures of kyphosis, or forward head posture, in individuals with hyperkyphosis at baseline (defined as angle of kyphosis ≥40°). Reviews, letters, notes, and non-English language studies were excluded.

Data Extraction

A pilot-tested abstraction form was used by each reviewer to extract data from each study regarding details of exercise intervention, participant characteristics, safety, adherence, and results. The Cochrane Collaboration's tool for assessing risk of bias was used to assess methodologic quality. Discrepancies on the abstraction forms between the 2 reviewers were resolved by a third reviewer. A formal meta-analysis was not performed.

Data Synthesis

Thirteen studies were abstracted and included in the review; of these, 8 studies saw improvements in ≥1 measure of posture. The main sources of bias were related to blinding participants and incomplete outcome data. The adherence reported across studies suggests that exercise is an acceptable intervention for individuals with age-related hyperkyphosis.

Conclusions

The scarcity and quality of available data did not permit a pooled estimate of the effect of exercise on hyperkyphotic posture; however, the positive effects observed in high-quality studies suggest some benefit and support the need for an adequately designed randomized controlled trial examining the effect of exercise on hyperkyphosis.     

Nighttime intensivist staffing and the timing of death among ICU decedents: a retrospective cohort study

Introduction

Intensive care units (ICUs) are increasingly adopting 24-hour intensivist physician staffing. Although nighttime intensivist staffing does not consistently reduce mortality, it may affect other outcomes such as the quality of end-of-life care.

Methods

We conducted a retrospective cohort study of ICU decedents using the 2009–2010 Acute Physiology and Chronic Health Evaluation clinical information system linked to a survey of ICU staffing practices. We restricted the analysis to ICUs with high-intensity daytime staffing, in which the addition of nighttime staffing does not influence mortality. We used multivariable regression to assess the relationship between nighttime intensivist staffing and two separate outcomes potentially related to the quality of end-of-life care: time from ICU admission to death and death at night.

Results

Of 30,456 patients admitted to 27 high-intensity daytime staffed ICUs, 3,553 died in the hospital within 30 days. After adjustment for potential confounders, admission to an ICU with nighttime intensivist staffing was associated with a shorter duration between ICU admission and death (adjusted difference: –2.5 days, 95% CI -3.5 to -1.5, p-value < 0.001) and a decreased odds of nighttime death (adjusted odds ratio: 0.75, 95% CI 0.60 to 0.94, p-value 0.011) compared to admission to an ICU without nighttime intensivist staffing.

Conclusions

Among ICU decedents, nighttime intensivist staffing is associated with reduced time between ICU admission and death and reduced odds of nighttime death.     

Longitudinal effects of weight loss and regain on cytokine concentration of obese adults

Objective

To describe patterns of weight loss and regain and their effect on the pro-inflammatory cytokines IL-6 and TNF-α, and anti-inflammatory cytokines adiponectin and IL-10 during a 24-month weight loss trial.

Materials/Methods

Participants were obese adults (N = 66) who lost and regained ≥ 10 lb during a 24-month clinical trial of behavioral weight loss treatment. Measurements of cytokines and weight were conducted at baseline, 6, 12, 18, and 24 months. Linear mixed modeling was used to determine percent change in weight and cytokines from baseline.

Results

The sample was predominantly female (80.3%) and White (86.4%), with a mean age of 48.4 ± 7.3 years and mean BMI of 34.5 ± 4.4 kg/m². At baseline, men had higher waist circumference, body weight, and energy intake, and lower percent body fat and adiponectin. The largest decrease in weight was observed at 6 months with a mean 11% decrease (p < .0001).A significant gender-by-weight change interaction on percent change in adiponectin was observed [b(se) = 0.9 (0.2), p = .0003], with men having a larger increase in adiponectin with weight loss compared to women. There was a significant effect of weight gain over time with increases in IL-6 [b(se) = 0.9 (0.3), p = .001].

Conclusions

Overall, weight loss was significantly associated with improvements in adiponectin and IL-6. Those improvements remained at 24 months, following weight regain. The association between weight change and adiponectin was different between genders. Implementing strategies that support sustained weight loss can help prevent a state of chronic systemic inflammation and its associated adverse effects.     

Effect of Bright Light Exposure on Depression and Agitation in Older Adults with Dementia

This study examined the effects of bright light exposure on three measures of depression and four measures of agitation in persons with dementia residing in long-term care. Using a randomized controlled design, participants were randomly assigned to receive either bright light (n = 30) or low intensity light (n = 30) for eight weeks. Bright light exposure was associated with significant improvement in depression and agitation, while participants receiving low intensity light displayed higher levels of depression and agitation or no significant change. Findings support the use of bright light exposure to reduce depression and agitation in this population.     

Low-grade squamous intraepithelial lesions of the cervix with marked cytological atypia-clinical follow-up and human papillomavirus genotyping.

The majority of low-grade squamous intraepithelial lesions (LSILs) of the cervix regress spontaneously; however, a small proportion of LSILs progress to high-grade squamous intraepithelial lesion (HSIL) if the lesion is not excised. The guidelines for which patients with LSIL should be treated and which may be followed safely are not well established. The goal of this study was to identify a subgroup of patients with LSIL who may require surgical treatment. We hypothesized that patients with LSILs with marked cytological atypia (LSIL-MA) may be at higher risk for subsequent HSIL. In addition, we were interested in whether LSIL-MA was associated with specific human papillomavirus genotypes. Consecutive patients with biopsy diagnosis of LSIL (n = 30) and LSIL-MA (n = 30) were identified. Marked atypia was defined as 5 or more cells with nuclear enlargement of at least 5 times the size of an intermediate cell nucleus or multinucleation with 5 or more nuclei. Patient follow-up was recorded for up to 24 months. Human papillomavirus genotyping was performed using SPF10 PCR and line probe assay. High-grade squamous intraepithelial lesion on follow-up was significantly more common in patients with LSIL-MA (36%) than in patients with LSIL (7%), and negative follow-up was significantly more common in patients with LSIL (50%) than LSIL-MA (23%). Cases of LSIL and LSIL-MA showed similar spectrum of human papillomavirus genotypes. Marked cytological atypia in LSILs identifies a subset of patients with a high rate of HSIL on follow-up. In such patients, an excisional cone biopsy should be strongly considered.     

Enteral nutrition and drug administration, interactions, and complications.

The enteral route has become the standard of care to deliver nutrition support for hospitalized acute care and ambulatory care patients. The same access device is increasingly being used to deliver medications, which provides cost savings but also creates new challenges. Cost savings can be negated if the concomitant administration of nutrition elicits a decrease in bioavailability due to incompatibilities that alter drug or nutrition therapy. Feeding tubes can deliver nutrients and drugs to the stomach, small bowel, or both, with optimal efficacy of medications depending on delivery to the appropriate segment of the gastrointestinal tract. Liquid preparations are often the preferred formulation for enteral administration. Obstruction of the enteral access device may occur when specialized medication formulations are altered inappropriately. Occasionally, the enteral formula should be changed to modify the content of free water, fiber, electrolytes, or vitamins that may interfere with the drug therapy. Intolerance to enteral nutrition such as abdominal distention and diarrhea may be the result of the medication, and the causative agent should be identified to improve patient comfort. This article will address optimal drug delivery via enteral access devices and possible complications associated with therapy.