Naltrexone implants -- duration, tolerability and clinical usefulness. A pilot study

Naltrexone blocks opioid effects effectively, but poor compliance limits the clinical usefulness in the treatment of opioid dependence. Long-acting implanted formulations might increase the clinical feasibility. Several implants have been produced, but few clinical reports have been published. This paper describes an open trial with an Australian implant. This implant is claimed to have duration of up to six months with double implants and acceptable levels of side effects. This was explored in the present pilot study with 13 opioid-dependent patients. By single implant of 1.8 g naltrexone the duration judged by naltrexone plasma levels above 1 ng/ml naltrexone was between 2 and 4 months. Double implants maintained such plasma levels for 5-6.5 months. Clinically, the implants appeared promising. Side effects were minimal. During the period with adequate plasma levels of naltrexone, use of opioids was absent and use of other psychoactive drugs reduced. At 1-year follow-up, the patients rated the implants highly positively.     

Development and validation of a magneto-hydrodynamic solver for blood flow analysis

The objective of this study was to develop a numerical solver to calculate the magneto-hydrodynamic (MHD) signal produced by a moving conductive liquid, i.e. blood flow in the great vessels of the heart, in a static magnetic field. We believe that this MHD signal is able to non-invasively characterize cardiac blood flow in order to supplement the present non-invasive techniques for the assessment of heart failure conditions. The MHD signal can be recorded on the electrocardiogram (ECG) while the subject is exposed to a strong static magnetic field. The MHD signal can only be measured indirectly as a combination of the heart's electrical signal and the MHD signal. The MHD signal itself is caused by induced electrical currents in the blood due to the moving of the blood in the magnetic field. To characterize and eventually optimize MHD measurements, we developed a MHD solver based on a finite element code. This code was validated against literature, experimental and analytical data. The validation of the MHD solver shows good agreement with all three reference values. Future studies will include the calculation of the MHD signals for anatomical models. We will vary the orientation of the static magnetic field to determine an optimized location for the measurement of the MHD blood flow signal.     

Thoracic impedance changes measured via defibrillator pads can monitor ventilation in critically ill patients and during cardiopulmonary resuscitation

OBJECTIVE: Monitoring of ventilation performance during cardiopulmonary resuscitation would be desirable to improve the quality of cardiopulmonary resuscitation. To investigate the potential for measuring ventilation rate and inspiration time, we calculated the correlation in waveform between transthoracic impedance measured via defibrillator pads and tidal volume given by a ventilator. DESIGN: Clinical study. SETTING: Emergency department of a tertiary care university hospital. PATIENTS: A convenience sample of mechanical ventilated patients (n = 32), cardiac arrest patients (n = 20), and patients after restoration of spontaneous circulation (n = 31) older than 18 were eligible. INTERVENTIONS: The Heartstart 4000SP defibrillator (Laerdal Medical Cooperation, Stavanger, Norway) with additional capabilities of recording thoracic impedance changes was used. MEASUREMENTS AND MAIN RESULTS: The relationship between impedance change and tidal volume (impedance coefficient) was calculated. The mean (sd) correlations between the impedance waveform and the tidal volume waveform in the patient groups studied were .971 (.027), .969 (.032), and .967 (.035), respectively. The mean (sd) impedance coefficient for all patients in the study was .00194 (.0078) Omega/mL, and the mean (sd) specific (weight-corrected) impedance coefficient was .152 (.048) Omega/kg/mL. The measured thorax impedance change for different tidal volumes (400-1000 mL) was approximately linear. CONCLUSIONS: The impedance sensor of a defibrillator is accurate in identifying tidal volumes, when chest compressions are interrupted. This also allows quantifying ventilation rates and inspiration times. However this technology, at its present state, provides only limited practical means for exact tidal volume estimation.     

Four-shell ellipsoidal model employing multipole expansion in ellipsoidal coordinates

Although the head is more closely represented as an ellipsoid than a sphere, calculation in ellipsoidal coordinates is difficult. This paper presents a four shell ellipsoidal model, employing multipole expansion in ellipsoidal coordinates, for EEG, MEG, and evoked potential applications. Computational detail and insight into efficient calculation of the Lamé functions of the first and second kind are provided to demonstrate feasibilty. The Lamé function of the second kind, derived from the Lamé function of the first kind, can be computed at higher degrees by means of partial fraction expansion.     

A 4-year follow-up of patients with medication-overuse headache previously included in a randomized multicentre study

The aim of this study was to evaluate the long-term outcome in 61 patients with medication-overuse headache (MOH) who 4 years previously had been included in a randomized open-label prospective multicentre study. Sixty patients still alive after 4 years were invited to a follow-up investigation. Fifty patients (83%) participated. Sixteen visited a neurologist, 22 were interviewed through telephone, 2 gave response by a letter, and 10 were evaluated through hospital records. The influence of baseline characteristics on outcome 4 years later was evaluated by non-parametric tests. p values below 0.01 were considered significant. At follow-up, the 50 persons had a mean reduction of 6.5 headache days/month (p < 0.001) and 9.5 acute headache medication days/month (p < 0.001) compared to baseline. Headache index/month was reduced from 449 to 321 (p < 0.001). Sixteen persons (32%) were considered as responders due to a ≥50% reduction in headache frequency from baseline, whereas 17 (34%) persons met the criteria for MOH. None of the baseline characteristics consistently influenced all five outcome measures. Total Hospital Anxiety and Depression Scale (HADS) score at baseline was predictors (p < 0.005) for being a responder after 4 years. At 4 years’ follow-up, one-third of the 50 MOH patients had ≥50% reduction in headache frequency from baseline. A low total HADS score at baseline was associated with the most favorable outcome.     

ω-3 Fatty Acid Treatment in Multiple Sclerosis (OFAMS Study): A Randomized, Double-Blind, Placebo-Controlled Trial

OBJECTIVE To investigate whether ω-3 fatty acids reduce magnetic resonance imaging (MRI) and clinical disease activity in patients with multiple sclerosis, both as monotherapy and in combination with interferon beta-1a treatment. DESIGN Multicenter, randomized, double-blind, placebo-controlled clinical trial conducted from 2004 to 2008. SETTING Thirteen public neurology departments in Norway. PARTICIPANTS Patients aged 18 to 55 years with active relapsing-remitting multiple sclerosis, with a disability score equivalent to 5.0 or less on the Kurtzke Expanded Disability Status Scale. Ninety-two patients were randomized to ω-3 fatty acids (n?=?46) or placebo capsules (n?=?46). INTERVENTIONS Administration of 1350 mg of eicosapentaenoic acid and 850 mg of docosahexaenoic acid daily or placebo. After 6 months, all patients in addition received subcutaneously 44 μg of interferon beta-1a 3 times per week for another 18 months. MAIN OUTCOME MEASURE The primary outcome measure was MRI disease activity as measured by the number of new T1-weighted gadolinium-enhancing lesions during the first 6 months. Secondary outcome measures included MRI disease activity after 9 months and 24 months, relapse rate, disability progression, fatigue, quality of life, and safety. RESULTS The cumulative number of gadolinium-enhancing MRI lesions during the first 6 months were similar in the ω-3 fatty acids and placebo groups (median difference, 1; 95% CI, 0 to 3; P?=?.09). No difference in relapse rate was detected after 6 (median difference, 0; 95% CI, 0 to 0; P?=?.54) or 24 (median difference, 0; 95% CI, 0 to 0; P?=?.72) months. The proportion of patients without disability progression was 70% in both groups (P?>?.99). No differences were detected in fatigue or quality-of-life scores, and no safety concerns appeared. Serum analyses of fatty acids showed an increase in ω-3 fatty acids (mean difference, 7.60; 95% CI, 5.57 to 7.91; P?<?.001) in the patients treated with ω-3 fatty acids compared with the placebo group. CONCLUSION No beneficial effects on disease activity were detected from ω-3 fatty acids when compared with placebo as monotherapy or in combination with interferon beta-1a. Magnetic resonance imaging disease activity was reduced as expected by interferon beta-1a. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00360906.     

Morphologic changes in tubular cells from in situ kidneys following experimental hypothermia and rewarming

Although renal failure may occur following rewarming from deep accidental hypothermia, this subject has received little attention in experimental hypothermia and clinical case reports. In order to explore the integrity of hypothermic and posthypothermic renal morphology we used an experimental animal model of accidental hypothermia where the heart supports the circulation throughout cooling and rewarming without accompanying cardioplegia or ischemia. Ultrastructural changes in renal tubular cells from three groups of pentobarbital anesthetized Wistar rats: 1) controls (n=6) maintained at 37 degrees C for 4 h, 2) hypothermic rats (n=6) core-cooled and maintained at 15-13 degrees C for 4 h, and 3) rewarmed rats (n=10), were studied as a sensitive indicator of renal damage. Electron micrographs (EM) from hypothermic kidneys showed rounded up mitochondria with loss of contrast. These changes were observed in several though not all of the biopsies, but they were found in all kidneys. Areas exhibiting focal tubular necrosis were seen on most EM from three of these kidneys. EM from rewarmed kidneys showed alterations of mitochondrial ultrastructure with similarities to those observed after hypothermia, but in general the changes were more prominent. Extracellular edema, intracellular edema, swelling of mitochondria, margination of chromatin, necrosis of single tubular cells, and disrupting necrotic debris into tubular lumen could be found in micrographs from 7 of the 10 kidneys examined. Rewarming from experimental hypothermia, without episodes of ischemia or hypoxia, thus induces ultrastructural changes in renal tubular cells similar to changes observed in acute tubular necrosis, associated with renal failure.