Case Study of an Employment Program for Recovering Alcoholics

The study design called for a longitudinal evaluation of one hundred subjects enrolled in a vocational counseling program for recovering alcoholics. Due to CETA stipend cuts, and slowing of referrals, eighty subjects were studied. Subjects were administered two questionnaires, one at program entry, the second at a six month follow-up point. The study's primary purpose was to identify those factors associated with success. Success was defined as diminution or elimination of the problem drinking pattern and employment at follow-up. A number of hypotheses were tested. The study was carried out over the course of twenty-three months. The mean age for subjects was 41. There were sixty-one men and nineteen women, 28% were members of a minority group. Subjects were typical of clinical treatment samples, more socially and psychologically impaired than a cross-section of the general drinking population. The majority were referred to the program by out-patient treatment facilities. Seventy-seven percent of the subjects mailed in their follow-up questionnaire. At follow-up the rate of employment was 56%. Employment was associated with the following factors: Program completion, younger age, some college education or beyond, abstinence or controlled drinking, higher rates of religious participation. Women and minority members were as successful in securing jobs as white males. The majority of the subjects were abstinent, with 13% problem drinking. Abstinence or controlled drinking was associated with the following factors: Employment, older age, minority group membership, no use of other drugs. Comparing employed with unemployed subjects, we found the unemployed were more likely to be drinking, and were experiencing higher rates of depression. Few subjects had strong family or friendship ties. Counselors' predictions of subject performance reflected a favorable bias toward subjects with particular characteristics. Predictions had a high rate of accuracy, raising questions about the effect of counselor bias on subject performance. Overall, subjects rated the impact of the program high to moderately high

Electrophysiologic Biomarkers for Assessing Disease Progression and the Effect of Riluzole in SOD1 G93A ALS Mice

Objective: To compare electrical impedance myography (EIM) 50 kHz phase to weight, motor score, paw grip endurance (PGE), CMAP amplitude, and MUNE for the identification of disease progression and the effect of riluzole in the SOD1 G93A mouse. Methods: Twenty-three animals received 8 mg/kg/day riluzole in the drinking water starting at 6 weeks of age; 22 animals served as controls. Weight, motor score, PGE, CMAP, MUNE, and EIM were performed weekly to evaluate disease progression. Results: No difference in clinical disease onset or survival was found between treated and untreated groups. In addition, all methods failed to identify any beneficial effect of riluzole. Thus, data from all animals were combined for additional analyses. Of the 4 parameters, EIM phase showed the earliest change from baseline and the most linear decline throughout the entire measurement period. In addition, EIM phase correlated with PGE, CMAP amplitude, and MUNE (Spearman r = 0.92, 0.90, and 0.72, respectively, p<0.01 for all). The rate of EIM phase decline also correlated with individual animal survival (Spearman r = −0.31, p<0.05). Conclusions: At this dose, riluzole is ineffective in slowing progression of ALS. However, EIM phase shows early linear declines, supporting its potential as a useful new biomarker for preclinical drug testing

Critical appraisal of the use of alpha lipoic acid (thioctic acid) in the treatment of symptomatic diabetic polyneuropathy

Courtney E McIlduff, Seward B RutkoveDepartment of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, USABackground: The most common of the neuropathies associated with diabetes mellitus, diabetic sensorimotor polyneuropathy (DSPN) is a syndrome of diffuse, length-dependent, symmetric nerve dysfunction. The condition is linked with substantial morbidity, frequent healthcare utilization, and compromised quality of life due to related discomfort. Correspondingly, antidepressants, anticonvulsants, and opioids are regularly prescribed with the goal of pain control. However, the agents rarely provide complete pain relief and fail to address progression of the disorder. Whereas strict blood glucose control can slow the onset and worsening of DSPN, near-normoglycemia is not easily attainable. Evidence implicating oxidative processes in the pathogenesis of DSPN offers one potentially important therapeutic avenue. Due to its properties as a potent antioxidant, alpha lipoic acid (ALA) could mitigate the development of DSPN and attenuate resultant symptoms and signs. Approved for treatment of DSPN in Germany, the agent is not more widely used due to uncertainty about its efficacy and reported adverse effects. Here we review the effectiveness and tolerability of ALA in the treatment of symptomatic DSPN.Methods: The MEDLINE, EMBASE, and Cochrane Library databases were searched for English-language literature on the topic. Randomized, blinded studies comparing parenteral and oral ALA with placebo in the treatment of peripheral neuropathy in diabetic adults were selected. Analysis included studies with a level of evidence of at least 2b.Results: The current appraisal summarizes data from 1160 participants in the ALADIN, SYDNEY, ORPIL, SYDNEY 2, and ALADIN III trials. In four of the studies, ALA provided significant improvement in manifestations of DSPN.Conclusion: Treatment with ALA 600 mg iv daily for 3 weeks represents a well-tolerated and effective therapy for DSPN. An oral dose of 600 mg daily administered for up to 5 weeks could offer benefits in symptoms and signs of DSPN without significant side effects.Keywords: alpha lipoic acid, antioxidant, diabetes mellitus, neuropathy, thioctic aci

Impaired Distal Thermoregulation in Diabetes and Diabetic Polyneuropathy

Objective: To determine how thermoregulation of the feet is affected by diabetes and diabetic polyneuropathy in both wakefulness and sleep. Research Design and Methods: Normal subjects, diabetic subjects without neuropathy, diabetic subjects with small-fiber diabetic polyneuropathy, and those with advanced diabetic polyneuropathy were categorized based on neurological examination, nerve conduction studies, and quantitative sensory testing. Subjects underwent foot temperature monitoring using an iButton device attached to the foot and a second iButton for recording of ambient temperature. Socks and footwear were standardized, and subjects maintained an activity diary. Data were collected over a 32-h period and analyzed. Results: A total of 39 normal subjects, 28 patients with diabetes but without diabetic polyneuropathy, 14 patients with isolated small-fiber diabetic polyneuropathy, and 27 patients with more advanced diabetic polyneuropathy participated. No consistent differences in foot temperature regulation between the four groups were identified during wakefulness. During sleep, however, multiple metrics revealed significant abnormalities in the diabetic patients. These included reduced mean foot temperature (P < 0.001), reduced maximal temperature (P < 0.001), increased rate of cooling (P < 0.001), as well as increased frequency of variation (P = 0.005), supporting that patients with diabetic polyneuropathy and even those with only diabetes but no diabetic polyneuropathy have impaired nocturnal thermoregulation. Conclusions: Nocturnal foot thermoregulation is impaired in patients with diabetes and diabetic polyneuropathy. Because neurons are highly temperature sensitive and because foot warming is part of the normal biology of sleep onset and maintenance, these findings suggest new potentially treatable mechanisms of diabetes-associated nocturnal pain and sleep disturbance

Cold Exposure Exacerbates the Development of Diabetic Polyneuropathy in the Rat

Diabetic polyneuropathy (DPN) and cold-induced nerve injury share several pathogenic mechanisms. This study explores whether cold exposure contributes to the development of DPN. Streptozotocin-induced diabetic rats and controls were exposed to a room temperature (23°C) or cold environment (10°C). H-reflex, tail and sciatic motor, and sensory nerve conduction studies were performed. Analyses of sural nerve, intraepidermal nerve fibers, and skin and nerve nitrotyrosine ELISAs were performed. Diabetic animals exposed to a cold environment had an increased H-reflex four weeks earlier than diabetic room temperature animals (P = .03). Cold-exposed diabetic animals also had greater reduction in motor conduction velocities at 20 weeks (P = .017), decreased skin nerve fiber density (P = .037), and increased skin nitrotyrosine levels (P = .047). Cold exposure appears to hasten the development of DPN in the rat STZ model of diabetes. These findings support that further study into the relationship between ambient temperature and DPN is warranted

Optimizing Electrode Configuration for Electrical Impedance Measurements of Muscle via the Finite Element Method

Electrical impedance myography (EIM) is a technique for the evaluation of neuromuscular diseases, including amyotrophic lateral sclerosis and muscular dystrophy. In this study, we evaluated how alterations in the size and conductivity of muscle and thickness of subcutaneous fat impact the EIM data, with the aim of identifying an optimized electrode configuration for EIM measurements. Finite element models were developed for the human upper arm based on anatomic data; material properties of the tissues were obtained from rat and published sources. The developed model matched the frequency-dependent character of the data. Of the three major EIM parameters, resistance, reactance, and phase, the reactance was least susceptible to alterations in the subcutaneous fat thickness, regardless of electrode arrangement. For example, a quadrupling of fat thickness resulted in a 375% increase in resistance at 35 kHz but only a 29% reduction in reactance. By further optimizing the electrode configuration, the change in reactance could be reduced to just 0.25%. For a fixed 30 mm distance between the sense electrodes centered between the excitation electrodes, an 80 mm distance between the excitation electrodes was found to provide the best balance, with a less than 1% change in reactance despite a doubling of subcutaneous fat thickness or halving of muscle size. These analyses describe a basic approach for further electrode configuration optimization for EIM

A Technique for Performing Electrical Impedance Myography in the Mouse Hind Limb: Data in Normal and ALS SOD1 G93A Animals

Objective: To test a method for performing electrical impedance myography (EIM) in the mouse hind limb for the assessment of disease status in neuromuscular disease models. Methods: An impedance measuring device consisting of a frame with electrodes embedded within an acrylic head was developed. The head was rotatable such that data longitudinal and transverse to the major muscle fiber direction could be obtained. EIM measurements were made with this device on 16 healthy mice and 14 amyotrophic lateral sclerosis (ALS) animals. Repeatability was assessed in both groups. Results: The technique was easy to perform and provided good repeatability in both healthy and ALS animals, with intra-session repeatability (mean ± SEM) of 5% ±1% and 12% ±2%, respectively. Significant differences between healthy and ALS animals were also identified (e.g., longitudinal mean 50 kHz phase was 18±0.6° for the healthy animals and 14±1.0° for the ALS animals, p = 0.0025). Conclusions: With this simple device, the EIM data obtained is highly repeatable and can differentiate healthy from ALS animals. Significance: EIM can now be applied to mouse models of neuromuscular disease to assess disease status and the effects of therapy

Impedance alterations in healthy and diseased mice during electrically induced muscle contraction

Alterations in the health of muscles can be evaluated through the use of electrical impedance myography (EIM). To date, however, nearly all work in this field has relied upon the measurement of muscle at rest. To provide an insight into the contractile mechanisms of healthy and disease muscle, we evaluated the alterations in the spectroscopic impedance behavior of muscle during the active process of muscle contraction. The gastrocnemii from a total of 13 mice were studied (five wild type, four muscular dystrophy animals, and four amyotrophic lateral sclerosis animals). Muscle contraction was induced via monophasic current pulse stimulation of the sciatic nerve. Simultaneously, multisine EIM (1 kHz to 1 MHz) and force measurements of the muscle were performed. Stimulation was applied at three different rates to produce mild, moderate, and strong contractions. We identified changes in both single and multifrequency data, as assessed by the Cole impedance model parameters. The processes of contraction and relaxation were clearly identified in the impedance spectra and quantified via derivative plots. Reductions in the center frequency f(c) were observed during the contraction consistent with the increasing muscle fiber diameter. Different EIM stimulation rate-dependencies were also detected across the three groups of animals.Peer ReviewedPostprint (author's final draft

ALS Longitudinal Studies With Frequent Data Collection at Home: Study Design and Baseline Data

Objective: To design an ALS clinical study in which patients are remotely recruited, screened, enrolled and then assessed via daily data collection at home by themselves or caregivers. Methods: This observational, natural-history study included two academic medical centers, one providing overall clinical management and the other overseeing computing and web-services design and management. Both healthy and ALS subjects were recruited on the Internet via advertisement on governmental and foundation websites as well as through Facebook and Google paid advertisements. Individuals underwent screening and enrollment remotely, including signing an electronic informed consent form. Participants were then provided self-measurement equipment and instructed on their use through a series of web-based videos. The equipment included a handgrip dynamometer, spirometer with smartphone connection, electrical impedance myography device, and an activity tracker. ALS Functional Rating Scale-Revised data were also collected. Subjects were asked to collect data daily for three months and twice-weekly for the subsequent six months. Results: One hundred and eleven ALS patients and 30 healthy individuals enrolled in the study from across 41 states (74 men, 62 women). Baseline median ALSFRS-R score was 33. Seventy two percent of the ALS patients sent equipment and 88% of the healthy subjects sent equipment were able to complete a first set of measurements. Expected baseline differences between the ALS patients and healthy participants were identified for all measures. Conclusions: It is possible to design and institute an at-home based study in ALS patients, using a number of state-of-the-art approaches, including web-based consenting and training and Internet-connected measurement devices