Effect of Rivastigmine on Mobility of Patients with Higher-Level Gait Disorder: A Pilot Exploratory Study

Background

Higher-level gait disorder (HLGD) in older adults is characterized by postural instability, stepping dysrhythmicity, recurrent falls and progressive immobility. Cognitive impairments are frequently associated with HLGD.

Objectives

The aim of this study was to compare gait and cognitive performance before and after the use of rivastigmine in patients with HLGD, free from cognitive impairment or Parkinsonism.

Methods

Fifteen non-demented patients with HLGD (age 79.2 ± 5.9 years; 11 women; Mini-Mental State Examination [MMSE] 28.3 ± 1.4) received escalating doses of rivastigmine for 12 weeks in an open-label, pilot study. They were assessed before and after treatment (week 0 and week 12), and after a 4-week washout period (week 16). Assessments included the Mindstreams computerized neuropsychological battery, Activities-specific Balance Confidence Scale, State-Trait Anxiety Inventory, Geriatric Depression Scale, Timed Up and Go (TUG) test, gait speed and stride time variability. One-way multiple analysis of variance tests for repeated measures were used, and Pillai’s trace test was considered as robust to investigate significant differences.

Results

The mean dose of rivastigmine during the 8–12 week period was 5.1 ± 2.3 mg/day. A positive effect was observed on the Mindstreams memory subscale and anxiety scores [Pillai’s trace: F(6,724) = 0.508, p = 0.010; and F(7,792) = 0.545, p = 0.006, respectively, over the course of the study] as well as on mobility (TUG test) [Pillai’s trace: F(4,863) = 0.448; p = 0.028], whereas gait speed and stride time variability did not change.

Conclusions

The use of relatively low-dose rivastigmine did not affect gait speed and stride time variability; however, the general mobility and anxiety were improved. These preliminary results warrant a larger, randomized, placebo-controlled study.     

Association of Bezafibrate Treatment With Reduced Risk of Cancer in Patients With Coronary Artery Disease

ObjectiveTo evaluate the association between bezafibrate, a drug used to treat hypertriglyceridemia, and long-term cancer incidence in patients with coronary artery disease (CAD).Patients and MethodsThe study comprised 2980 patients with CAD (mean age, 60 years; 2729 [91.6%] men) who were free of cancer and were enrolled in the Bezafibrate Infarction Prevention study, a double-blind trial conducted between May 1, 1990, and January 31, 1993, in 18 cardiology departments in Israel. Patients randomized to receive 400 mg of bezafibrate (n=1486) or placebo (n=1494) daily for a median of 6.2 years (range, 4.7-7.6 years) were followed up for incidence of cancer through the Israeli National Cancer Registry and all-cause death through the Population Registry of the State of Israel until December 31, 2013. Cox proportional hazards and Fine and Gray survival models were used to assess the bezafibrate-cancer association.ResultsClinical characteristics and laboratory values were well balanced between the 2 groups at the study entry. Over a median follow-up of 22.5 years (range, 21.2-23.9 years), cancer developed in 753 patients. With death considered a competing event, the cumulative incidence of cancer at the end of the follow-up was lower in the bezafibrate vs the placebo group (23.9%; 95 CI, 21.9%-26.1% vs 27.2%; 95 CI, 25.1%-29.4%; P=.04). The hazard ratio for cancer in the bezafibrate vs placebo groups was 0.86 (95% CI, 0.74-0.99). In mediation analysis, the association between bezafibrate treatment and cancer incidence was not sensitive to adjustment for on-trial lipid levels but was attenuated on adjustment for on-trial fibrinogen levels.ConclusionBezafibrate treatment is associated with reduced risk of cancer among patients with CAD. Fibrinogen, but not lipid lowering, is linked to this association.     

Deep Brain Stimulation for Disorders of Memory and Cognition

The next several decades will see an exponential rise in the number of patients with disorders of memory and cognition, and of Alzheimer’s disease in particular. Impending demographic shifts, an absence of effective treatments, and the significant burden these conditions place on patients, caregivers, and society, mean there is an urgent need to develop novel therapies. Deep brain stimulation (DBS) is a neurosurgical procedure that is a standard-of-care for many patients with treatment-refractory Parkinson’s disease, dystonia, and essential tremor. DBS has proven to be an effective means of modulating activity in disrupted motor circuitry, and has shown promise as a modulator of other dysfunctional circuits, including for mood and anxiety disorders. The deficits in Alzheimer’s disease and other disorders of memory and cognition are also beginning to be thought of as arising from dysfunction in neural circuits. Such dysfunction may be amenable to modulation using focal brain stimulation. A global experience is now emerging for the use of DBS for these conditions, targeting key nodes in the memory circuit, including the fornix and nucleus basalis of Meynert. Such work holds promise as a novel therapeutic approach for one of medicine’s most urgent priorities.     

Intracranial Applications of Magnetic Resonance-guided Focused Ultrasound

The ability to focus acoustic energy through the intact skull on to targets millimeters in size represents an important milestone in the development of neurotherapeutics. Magnetic resonance-guided focused ultrasound (MRgFUS) is a novel, noninvasive method, which—under real-time imaging and thermographic guidance—can be used to generate focal intracranial thermal ablative lesions and disrupt the blood–brain barrier. An established treatment for bone metastases, uterine fibroids, and breast lesions, MRgFUS has now been proposed as an alternative to open neurosurgical procedures for a wide variety of indications. Studies investigating intracranial MRgFUS range from small animal preclinical experiments to large, late-phase randomized trials that span the clinical spectrum from movement disorders, to vascular, oncologic, and psychiatric applications. We review the principles of MRgFUS and its use for brain-based disorders, and outline future directions for this promising technology.     

The effects of ambient particulate matter on human adipose tissue

ABSTRACT

The effects of particulate matter (PM) air pollution on adipose tissue have mainly been studied in animal models. The aim of this study was to examine the potential associations between PM exposure and 25 cellular markers in human omental (OM) and subcutaneous (SC) adipose tissue. The PM exposure assessments for both PM_2.5 (PM <2.5 μm in diameter) and PM₁₀ (<10 μm) were based upon a novel hybrid satellite-based spatio-temporally resolved model. We calculated the PM exposure above the background threshold for 1 week (acute phase), 3 and 6 months (intermediate phase), and 1 year (chronic phase) prior to tissue harvesting and tested the associations with adipose cell metabolic effects using multiple linear regressions and heat maps strategy. Chemokine levels were found to increase after acute and intermediate exposure duration to PM₁₀. The levels of stress signaling biomarkers in the SC and OM tissues rose after acute exposure to PM₁₀ and PM_2.5. Macrophage and leucocyte counts were associated with severity of PM exposure in all three duration groups. Adipocyte diameter decreased in all exposure periods. Our results provide evidence for significant contribution of air pollutants exposure to adipose tissue inflammation as well as for pathophysiological mechanisms of metabolic dysregulation that may be involved in the observed responses.     

EGFR Mutation Testing Practice in Advanced Non-Small Cell Lung Cancer

Purpose

Testing tumor samples for the presence of a mutation in the epithelial growth factor receptor (EGFR) gene is recommended for advanced non-squamous non-small cell lung cancer (NSCLC) patients. We aimed to collect data about common practice among Medical Oncologists treating lung cancer patients, regarding EGFR mutation testing in advanced NSCLC patients.

Methods

An internet-based survey was conducted among members of the Israeli Society for Clinical Oncology and Radiotherapy involved in the treatment of lung cancer patients.

Results

24 Oncologists participated in the survey. The participants encompass the Oncologists treating most of the lung cancer patients in Israel. 79 % of them use EGFR testing routinely for all advanced NSCLC patients. Opinions were split regarding the preferable biopsy site for EGFR testing material. 60 % of participants recommend waiting for EGFR test results prior to initiation of first-line therapy.

Conclusions

EGFR testing is requested in Israel routinely by most treating Oncologists for all advanced NSCLC patients, regardless of histology. In most cases, systemic treatment is deferred until the results of this test are received.     

Impact of Texting Laws on Motor Vehicular Fatalities in the United States

Using a panel study design, we examined the effects of different types of texting bans on motor vehicular fatalities.We used the Fatality Analysis Reporting System and a difference-in-differences approach to examine the incidence of fatal crashes in 2000 through 2010 in 48 US states with and without texting bans. Age cohorts were constructed to examine the impact of these bans on age-specific traffic fatalities.Primarily enforced laws banning all drivers from texting were significantly associated with a 3% reduction in traffic fatalities in all age groups, and those banning only young drivers from texting had the greatest impact on reducing deaths among those aged 15 to 21 years. Secondarily enforced restrictions were not associated with traffic fatality reductions in any of our analyses.Motor vehicle safety has been described as one of the 10 great public health achievements in the United States in the past decade,1 with car manufacturers and highway engineers making significant improvements to car and roadway safety features.2 Despite these improvements, traffic fatalities remain one of the leading causes of death in the United States,3 with an estimated 32 788 such deaths in 2010.4 Thus, road traffic fatalities continue to be a significant public health concern,5,6 garnering much attention from state lawmakers.In an effort to reduce motor vehicle fatalities, states have enacted restrictions on drunk driving, implemented graduated driver’s license programs, and mandated seatbelt use and special licensing procedures for older adults. Most recently, states have focused on restricting texting while driving.7–9 Generally, states define texting as reading, manual composition, or sending of electronic communications—text messages, instant messages, or e-mails—via a portable electronic device. Portable electronic devices include mobile (i.e., cellular) phones, personal digital assistants, and laptop computers. Texting while driving is a serious threat to road safety,10–13 given that research has shown that mobile phone use is associated with impaired following distance,14 improper lane position,11,15 longer reaction times,11,14,16 and crashes,11,17 which can all lead to significant adverse public health outcomes, including death.18 Unlike talking on a mobile phone while driving, texting poses a unique threat in that it requires drivers to take their eyes off the road for several seconds at a time.14Our current understanding of the impact of texting laws on driving outcomes is limited. To our knowledge, 2 studies have empirically examined the impact of texting laws on adverse motor vehicle outcomes. The first was published by the Highway Loss Data Institute.19 It examined the relationship of collision claim frequency and texting bans in just 4 states (CA, LA, MN, and WA). The authors found that texting bans were associated with increased collision claims. They speculated that this increase might be due to drivers hiding their phones from view to avoid fines and, in so doing, taking their eyes off the road more than they did before the bans. More recently, Abouk and Adams20 published the first national-level study of texting bans’ impacts on traffic fatalities. They examined the impact of texting-while-driving bans on the occurrence of only single-vehicle, single-occupant accidents between 2007 and 2010. Their findings indicated that stronger bans that are applied to all drivers were associated with decreases in single-vehicle, single-occupant accidents.The purpose of this study is to add to the knowledge base concerning the effectiveness of texting laws, particularly by considering the varying stringency levels of these laws. Texting bans can be secondarily enforced (i.e., an officer must have another reason to stop a vehicle before citing a driver for texting while driving) or primarily enforced (i.e., an officer does not have to have another reason for stopping a vehicle). Furthermore, some states ban texting among learner’s permit holders, and some ban texting among all those aged 18 years, 21 years, or younger, and still other states ban all drivers from texting. Some states have no texting laws at all. We consider the impact of each of these policy nuances on traffic fatalities in 48 states over an 11-year period. Moreover, given that younger individuals are more likely to text while driving,21 we examine the impact of texting laws on age-specific traffic fatalities. Overall, this study will be of interest to policymakers, law enforcement personnel, and other stakeholders interested in improving roadway safety and, by extension, public health.     

Mapping white matter integrity in elderly people with HIV

People with HIV are living longer as combination antiretroviral therapy (cART) becomes more widely available. However, even when plasma viral load is reduced to untraceable levels, chronic HIV infection is associated with neurological deficits and brain atrophy beyond that of normal aging. HIV is often marked by cortical and subcortical atrophy, but the integrity of the brain's white matter (WM) pathways also progressively declines. Few studies focus on older cohorts where normal aging may be compounded with HIV infection to influence deficit patterns. In this relatively large diffusion tensor imaging (DTI) study, we investigated abnormalities in WM fiber integrity in 56 HIV+ adults with access to cART (mean age: 63.9 ± 3.7 years), compared to 31 matched healthy controls (65.4 ± 2.2 years). Statistical 3D maps revealed the independent effects of HIV diagnosis and age on fractional anisotropy (FA) and diffusivity, but we did not find any evidence for an age by diagnosis interaction in our current sample. Compared to healthy controls, HIV patients showed pervasive FA decreases and diffusivity increases throughout WM. We also assessed neuropsychological (NP) summary z‐score associations. In both patients and controls, fiber integrity measures were associated with NP summary scores. The greatest differences were detected in the corpus callosum and in the projection fibers of the corona radiata. These deficits are consistent with published NP deficits and cortical atrophy patterns in elderly people with HIV. Hum Brain Mapp 35:975–992, 2014. © 2013 Wiley Periodicals, Inc.     

The reciprocal relationship between vigor and insomnia: a three-wave prospective study of employed adults

Vigor is a positive affect experienced at work. It refers to feelings of possessing physical strength, emotional energy, and cognitive liveliness. Accumulated evidence suggests that vigor has a protective effect on health, but the mechanisms of this link remain to be discovered. This study focused on sleep quality as one possible mechanism. We used a full-panel, longitudinal design to investigate the hypothesis that changes in vigor over time have inverse effects on insomnia and vice versa. The study was conducted on a multi-occupational sample of working adults (N = 1,414, 70 % men) at three time points (T1, T2, and T3), over a period of about 3 years. Vigor was assessed by the Shirom-Melamed Vigor Measure, while insomnia was assessed by the Brief Athens Insomnia Scale. Results of SEM-analyses, controlling for neuroticism, and other potential confounding variables, offered a strong support for the study hypotheses, indicating cross-lagged reciprocal inverse relationships between vigor and insomnia. The results suggest that vigor has a protective effect on sleep quality and that vigor might positively influence health through this pathway.