Comparison of dynamic susceptibility contrast (DSC) using gadolinium and iron-based contrast agents in high-grade glioma at high-field MRI.

PURPOSE: To compare DSC-MRI using Gadolinium (GBCA) and Ferumoxytol (FBCA) in high-grade glioma at 3T and 7T MRI field strengths. We hypothesized that using FBCA at 7T would enhance the performance of DSC, as measured by contrast-to-noise ratio (CNR). METHODS: Ten patients (13 lesions) were assigned to 3T (6 patients, 6 lesions) or 7T (4 patients, 7 lesions). All lesions received 0.1 mmol/kg of GBCA on day 1. Ten lesions (4 at 3T and 6 at 7T) received a lower dose (0.6 mg/kg) of FBCA, followed by a higher dose (1.0-1.2 mg/kg), while 3 lesions (2 at 3T and 1 at 7T) received only a higher dose on Day 2. CBV maps with leakage correction for GBCA but not for FBCA were generated. The CNR and normalized CBV (nCBV) were analyzed on enhancing and non-enhancing high T2W lesions. RESULTS: Regardless of FBCA dose, GBCA showed higher CNR than FBCA at 7T, which was significant for high-dose FBCA (p < .05). Comparable CNR between GBCA and high-dose FBCA was observed at 3T. There was a trend toward higher CNR for FBCA at 3T than 7T. GBCA also showed nCBV twice that of FBCA at both MRI field strengths with significance at 7T. CONCLUSION: GBCA demonstrated higher image conspicuity, as measured by CNR, than FBCA on 7T. The stronger T2* weighting realized with higher magnetic field strength, combined with FBCA, likely results in more signal loss rather than enhanced performance on DSC. However, at clinical 3T, both GBCA and FBCA, particularly a dosage of 1.0-1.2 mg/kg (optimal for perfusion imaging), yielded comparable CNR.

Meditation in Stressed Older Adults: Improvements in self-rated mental health not paralleled by improvements in cognitive function or physiological measures.

To determine if mindfulness meditation (MM) in older adults improves cognition and, secondarily, if MM improves mental health and physiology, 134 at least mildly stressed 50-85 year olds were randomized to a six-week MM intervention or a waitlist control. Outcome measures were assessed at baseline and two months later at Visit 2. The primary outcome measure was an executive function/attentional measure (flanker task). Other outcome measures included additional cognitive assessments, salivary cortisol, respiratory rate, heart rate variability, Positive and Negative Affect Schedule (PANAS), Center for Epidemiologic Studies Depression (CESD), Perceived Stress Scale (PSS), Neuroticism-Extraversion-Openness (NEO) personality traits, and SF-36 health-related quality of life. 128 participants completed the study though Visit 2 assessments. There was no significant change in the primary or other cognitive outcome measures. Even after statistical adjustment for multiple outcomes, self-rated measures related to negative affect and stress were all significantly improved in the MM intervention compared to wait-list group (PANAS-negative, CESD, PSS, and SF-36 health-related quality of life Vitality and Mental Health Component). The SF-36 Mental Health Component score improved more than the minimum clinically important difference. There were also significant changes in personality traits such as Neuroticism. Changes in positive affect were not observed. There were no group differences in salivary cortisol, or heart rate variability. These moderate sized improvements in self-rated measures were not paralleled by improvements in cognitive function or physiological measures. Potential explanations for this discrepancy in stress-related outcomes are discussed to help improve future studies.

Current and potential imaging applications of ferumoxytol for magnetic resonance imaging.

Contrast-enhanced magnetic resonance imaging is a commonly used diagnostic tool. Compared with standard gadolinium-based contrast agents, ferumoxytol (Feraheme, AMAG Pharmaceuticals, Waltham, MA), used as an alternative contrast medium, is feasible in patients with impaired renal function. Other attractive imaging features of i.v. ferumoxytol include a prolonged blood pool phase and delayed intracellular uptake. With its unique pharmacologic, metabolic, and imaging properties, ferumoxytol may play a crucial role in future magnetic resonance imaging of the central nervous system, various organs outside the central nervous system, and the cardiovascular system. Preclinical and clinical studies have demonstrated the overall safety and effectiveness of this novel contrast agent, with rarely occurring anaphylactoid reactions. The purpose of this review is to describe the general and organ-specific properties of ferumoxytol, as well as the advantages and potential pitfalls associated with its use in magnetic resonance imaging. To more fully demonstrate the applications of ferumoxytol throughout the body, an imaging atlas was created and is available online as supplementary material.

Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Systematic Review for a National Institutes of Health Pathways to Prevention Workshop.

BACKGROUND: Myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) is a debilitating multisystem condition affecting more than 1 million adults in the United States. PURPOSE: To determine benefits and harms of treatments for adults with ME/CFS and identify future research needs. DATA SOURCES: MEDLINE, PsycINFO, and Cochrane databases (January 1988 to September 2014); clinical trial registries; reference lists; and manufacturer information. STUDY SELECTION: English-language randomized trials of the effectiveness and adverse effects of ME/CFS treatments. DATA EXTRACTION: Data on participants, study design, analysis, follow-up, and results were extracted and confirmed. Study quality was dual-rated by using prespecified criteria; discrepancies were resolved through consensus. DATA SYNTHESIS: Among 35 treatment trials enrolling participants primarily meeting the 1994 Centers for Disease Control and Prevention and Oxford case definitions of CFS, the immune modulator rintatolimod improved some measures of exercise performance compared with placebo in 2 trials (low strength of evidence). Trials of galantamine, hydrocortisone, IgG, valganciclovir, isoprinosine, fluoxetine, and various complementary medicines were inconclusive (insufficient evidence). Counseling therapies and graded exercise therapy compared with no treatment, relaxation, or support improved fatigue, function, global improvement, and work impairment in some trials; counseling therapies also improved quality of life (low to moderate strength of evidence). Harms were rarely reported across studies (insufficient evidence). LIMITATION: Trials were heterogeneous and were limited by size, number, duration, applicability, and methodological quality. CONCLUSION: Trials of rintatolimod, counseling therapies, and graded exercise therapy suggest benefit for some patients meeting case definitions for CFS, whereas evidence for other treatments and harms is insufficient. More definitive studies comparing participants meeting different case definitions, including ME, and providing subgroup analysis are needed to fill research gaps.

Agency for Healthcare Research and Quality Evidence-based Practice Center methods for systematically reviewing complex multicomponent health care interventions.

OBJECTIVES: The purpose of this Agency for Healthcare Research and Quality Evidence-based Practice Center methods white paper was to outline approaches to conducting systematic reviews of complex multicomponent health care interventions. STUDY DESIGN AND SETTING: We performed a literature scan and conducted semistructured interviews with international experts who conduct research or systematic reviews of complex multicomponent interventions (CMCIs) or organizational leaders who implement CMCIs in health care. RESULTS: Challenges identified include lack of consistent terminology for such interventions (eg, complex, multicomponent, multidimensional, multifactorial); a wide range of approaches used to frame the review, from grouping interventions by common features to using more theoretical approaches; decisions regarding whether and how to quantitatively analyze the interventions, from holistic to individual component analytic approaches; and incomplete and inconsistent reporting of elements critical to understanding the success and impact of multicomponent interventions, such as methods used for implementation the context in which interventions are implemented. CONCLUSION: We provide a framework for the spectrum of conceptual and analytic approaches to synthesizing studies of multicomponent interventions and an initial list of critical reporting elements for such studies. This information is intended to help systematic reviewers understand the options and tradeoffs available for such reviews.

Pressure ulcer treatment strategies: a systematic comparative effectiveness review.

BACKGROUND: Pressure ulcers affect as many as 3 million Americans and are major sources of morbidity, mortality, and health care costs. PURPOSE: To summarize evidence comparing the effectiveness and safety of treatment strategies for adults with pressure ulcers. DATA SOURCES: MEDLINE, EMBASE, CINAHL, Evidence-Based Medicine Reviews, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, and Health Technology Assessment Database for English- or foreign-language studies; reference lists; gray literature; and individual product packets from manufacturers (January 1985 to October 2012). STUDY SELECTION: Randomized trials and comparative observational studies of treatments for pressure ulcers in adults and noncomparative intervention series (n > 50) for surgical interventions and evaluation of harms. DATA EXTRACTION: Data were extracted and evaluated for accuracy of the extraction, quality of included studies, and strength of evidence. DATA SYNTHESIS: 174 studies met inclusion criteria and 92 evaluated complete wound healing. In comparison with standard care, placebo, or sham interventions, moderate-strength evidence showed that air-fluidized beds (5 studies [n = 908]; high consistency), protein-containing nutritional supplements (12 studies [n = 562]; high consistency), radiant heat dressings (4 studies [n = 160]; moderate consistency), and electrical stimulation (9 studies [n = 397]; moderate consistency) improved healing of pressure ulcers. Low-strength evidence showed that alternating-pressure surfaces, hydrocolloid dressings, platelet-derived growth factor, and light therapy improved healing of pressure ulcers. The evidence about harms was limited. LIMITATION: Applicability of results is limited by study quality, heterogeneity in methods and outcomes, and inadequate duration to assess complete wound healing. CONCLUSION: Moderate-strength evidence shows that healing of pressure ulcers in adults is improved with the use of air-fluidized beds, protein supplementation, radiant heat dressings, and electrical stimulation.

Primary care-relevant interventions to prevent falling in older adults: a systematic evidence review for the U.S. Preventive Services Task Force.

BACKGROUND: Falls among older adults are both prevalent and preventable. PURPOSE: To describe the benefits and harms of interventions that could be used by primary care practitioners to prevent falling among community-dwelling older adults. DATA SOURCES: The reviewers evaluated trials from a good-quality systematic review published in 2003 and searched MEDLINE, the Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and CINAHL from the end of that review's search date to February 2010 to identify additional English-language trials. STUDY SELECTION: Two reviewers independently screened 3423 abstracts and 638 articles to identify randomized, controlled trials (RCTs) of primary care-relevant interventions among community-dwelling older adults that reported falls or fallers as an outcome. Trials were independently critically appraised to include only good- or fair-quality trials; discrepancies were resolved by a third reviewer. DATA EXTRACTION: One reviewer abstracted data from 61 articles into standardized evidence tables that were verified by a second reviewer. DATA SYNTHESIS: Overall, the included evidence was of fair quality. In 16 RCTs evaluating exercise or physical therapy, interventions reduced falling (risk ratio, 0.87 [95% CI, 0.81 to 0.94]). In 9 RCTs of vitamin D supplementation, interventions reduced falling (risk ratio, 0.83 [CI, 0.77 to 0.89]). In 19 trials involving multifactorial assessment and management, interventions with comprehensive management seemed to reduce falling, although overall pooled estimates were not statistically significant (risk ratio, 0.94 [CI, 0.87 to 1.02]). Limited evidence suggested that serious clinical harms were no more common for older adults in intervention groups than for those in control groups. LIMITATIONS: Interventions and methods of fall ascertainment were heterogeneous. Data on potential harms of interventions were scant and often not reported. CONCLUSION: Primary care-relevant interventions exist that can reduce falling among community-dwelling older adults. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Nonhormonal therapies for menopausal hot flashes: systematic review and meta-analysis.

CONTEXT: Concern regarding the adverse effects of estrogen and other hormones for treating menopausal symptoms has led to demand for other options; however, the efficacy and adverse effects of nonhormonal therapies are unclear. OBJECTIVE: To assess the efficacy and adverse effects of nonhormonal therapies for menopausal hot flashes by reviewing published randomized controlled trials. DATA SOURCES: MEDLINE (1966-October 2005), PsycINFO (1974-October 2005), and the Cochrane Controlled Clinical Trials Register Database (1966-October 2005) were searched for relevant trials that provided data on treatment of menopausal hot flashes using 1 or more nonhormonal therapies. STUDY SELECTION: All English-language, published, randomized, double-blind, placebo-controlled trials of oral nonhormonal therapies for treating hot flashes in menopausal women measuring and reporting hot flash frequency or severity outcomes. DATA EXTRACTION: Trials were identified, subjected to inclusion and exclusion criteria, and reviewed. Data on participants, interventions, and outcomes were extracted and trials were rated for quality based on established criteria. A meta-analysis was conducted for therapies with sufficient trials reporting hot flash frequency outcomes. DATA SYNTHESIS: From 4249 abstracts, 43 trials met inclusion criteria, including 10 trials of antidepressants, 10 trials of clonidine, 6 trials of other prescribed medications, and 17 trials of isoflavone extracts. The number of daily hot flashes decreased compared with placebo in meta-analyses of 7 comparisons of selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs) (mean difference, -1.13; 95% confidence interval [CI], -1.70 to -0.57), 4 trials of clonidine (-0.95; 95% CI, -1.44 to -0.47), and 2 trials of gabapentin (-2.05; 95% CI, -2.80 to -1.30). Frequency was not reduced in meta-analysis of trials of red clover isoflavone extracts and results were mixed for soy isoflavone extracts. Evidence of the efficacy of other therapies is limited due to the small number of trials and their deficiencies. Trials do not compare different therapies head-to-head and relative efficacy cannot be determined. CONCLUSION: The SSRIs or SNRIs, clonidine, and gabapentin trials provide evidence for efficacy; however, effects are less than for estrogen, few trials have been published and most have methodological deficiencies, generalizability is limited, and adverse effects and cost may restrict use for many women. These therapies may be most useful for highly symptomatic women who cannot take estrogen but are not optimal choices for most women.

Critical factors for bone health in women across the age span: how important is muscle mass?

OBJECTIVES/DESIGN: This cross-sectional study of 113 healthy white women, 20-88 years of age, evaluated relationships between bone mineral density (BMD), body composition, calcium (Ca) intake, and physical activity. The analysis was performed in the entire cohort and in groups divided by reproductive/menopausal status (premenopausal, perimenopausal, early postmenopausal, and late postmenopausal). METHODS: BMD and body composition were measured with Lunar DPX-MD densitometer using specialized software for total body, spine, femur, and forearm. Ca intake from food and supplements was assessed by a food frequency questionnaire. Past physical activity and past and present walking were assessed only in the older cohort using modified version of the Allied Dunbar National Fitness Survey for Older Adults. RESULTS: The results showed significant reduction of both total body BMD and lean body mass (LBM) of 13% and 12%, respectively, with age. LBM was the strongest determinant of BMD in various skeletal sites in the entire cohort and groups. Ca was positively associated with BMD of various regions of hip in the entire cohort and in the youngest and oldest subjects (r ranging from 0.32-0.56, P <.05, in simple regression), but not in perimenopausal and early postmenopausal women. Past activity (sports and recreation) was positively associated with BMD in total body, spine, hip, and forearm (r ranging from 0.26-0.37, P <.05). Various modes of present walking were positively associated with BMD in regions of femur and forearm. CONCLUSIONS: These results reveal the importance of lean tissue acting independently on bone at different skeletal sites in women across age groups as well as the positive effects on BMD of Ca in the youngest and oldest women and life-long engagement in physical activity in older women.