Depression and changed pain perception: hints for a central disinhibition mechanism

Although patients with a depressive disorder report often of pain, their sensitivity to experimental pain is controversial, probably due to differences in sensory testing methods and to the lack of normal values. Therefore, we used a standardized and validated comprehensive sensory testing paradigm to assess the peripheral and central nervous system performance in depressive patients compared to healthy controls and chronic pain patients with fibromyalgia syndrome (FMS), in which depression is a common comorbidity. Twenty-five depressive psychiatric inpatients (pain-free: n=20), 35 FMS outpatients and 25 healthy controls underwent quantitative sensory testing (QST), including thermal and mechanical detection and pain thresholds, pain sensitivity and responsiveness to repetitive noxious mechanical stimuli (wind-up). In depressive disorder (to a lesser extent also in FMS), significantly decreased cold pain thresholds and an increased wind-up were found, although the mechanical pain thresholds and pain sensitivity were comparable to those of the healthy controls. All the detection thresholds were within the normal range in all the groups. In depressive disorder, there were no significant side differences in the detection and pain thresholds. The results contradict the former assumption of a general insensitivity to experimental pain in depressive disorder. In the mostly pain-free patients signs of an enhanced central hyperexcitability are even more pronounced than usually found in chronic pain patients (e.g. FMS), indicating common mechanisms in depressive disorder and chronic pain in accordance with the assumption of non-pain associated mechanisms in depressive disorder for central hyperexcitability, e.g. by inhibited serotonergic function. Furthermore, this trial demonstrates the feasibility of QST in depressive patients.     

Optical mapping reveals conduction slowing and impulse block in iron-overload cardiomyopathy

Cardiac disease with arrhythmia or heart failure is the leading cause of death in patients with thalassemia major and a major complication of other forms of iron overload. Current antiarrhythmic treatment does not appear to alter the clinical course. Using a gerbil model of iron-overload cardiomyopathy, we previously observed a reduction in the fast inward sodium current in isolated cardiomyocytes. Electrocardiograms (ECGs) in the same gerbil model indicate PR-interval prolongation, QRS-interval widening, and arrhythmias. We hypothesize that such changes in the ECG in this model are the result of abnormal action-potential conduction at the level of the whole heart. To test this hypothesis, we took ECGs and recorded action potentials using high-resolution optical mapping from the anterior surface of 9 iron-overloaded and 9 age-matched control ventricular-paced, Langendorff-perfused gerbil hearts. The iron-overloaded gerbils received weekly iron-dextran injections of 800 mg/kg for 14 to 18 weeks. ECGs showed QRS- and PR-interval prolongation in iron-treated gerbils compared with that in controls. In addition, atrioventricular block was observed in 2 of 6 iron-treated gerbils but not in controls. Conduction velocity was significantly slower in iron-treated gerbils than in controls. At normal pacing rates, abnormal activation patterns caused by stable regions of conduction block were observed in iron-overloaded gerbils (33%) but not in controls. Such abnormal impulse conduction may be a mechanism of increased arrhythmia vulnerability in iron-overload cardiomyopathy.     

Safety, tolerability and symptom outcomes associated with L-carnitine supplementation in patients with cancer, fatigue, and carnitine deficiency: a phase I/II study

Carnitine deficiency is among the many metabolic disturbances that may contribute to fatigue in patients with cancer. Administration of exogenous L-carnitine may hold promise as a treatment for this common symptom. Little is known about L-carnitine safety, tolerability, and dose-response in patients with cancer. We conducted a Phase I/II open-label trial to assess the safety and tolerability of exogenous L-carnitine and clarify the safe dose range associated with symptom effects for future controlled trials. Adult patients with advanced cancer, carnitine deficiency (free carnitine <35 for males or <25 microM/L for females, or acyl/free carnitine ratio >0.4), moderate to severe fatigue, and a Karnofsky Performance Status (KPS) score > or =50 were entered by groups of at least three into a standard maximum tolerated dose design. Each successive group received a higher dose of L-carnitine (250, 750, 1250, 1750, 2250, 2750, 3000 mg/day, respectively), administered in two daily doses for 7 days. To compare symptom outcomes before and after supplementation, patients completed validated measures of fatigue (Brief Fatigue Inventory [BFI]), depressed mood (Center for Epidemiologic Studies Depression Scale [CES-D]), quality of sleep (Epworth Sleeplessness Scale [ESS]), and KPS at baseline and 1 week later. Of the 38 patients screened for carnitine levels, 29 were deficient (76%). Twenty-seven patients participated ("intention to treat, ITT") (17 males, 10 females), and 21 completed the study ("completers"); 17 of these patients ("responders," mean+/-[SD] age=57.9+/-15) had increased carnitine levels at the end of the supplementation period. The highest dose achieved was 3000 mg/day. No patient experienced significant side effects and no toxicities were noted. Analysis of all the patients accrued (ITT, n=27) showed a total carnitine increase from 32.8+/-10 to 54.3+/-23 microM/L (P<0.001) and free carnitine increase from 26.8+/-8 to 44.1+/-17 microM/L (P<0.001). BFI decreased significantly, from 66+/-12 to 39.7+/-26 (P<0.001); ESS decreased from 12.9+/-12 to 9+/-6 (P=0.001); and CES-D decreased from 29.2+/-12 to 19+/-12 (P<0.001). A separate analysis of the 17 "responders" showed a dose-response relationship for total- (r=0.54, P=0.03), free-carnitine (r=0.56, P=0.02) levels, and fatigue (BFI) scores (r=-0.61, P=0.01). These findings suggest that l-carnitine may be safely administered at doses up to 3000 mg/day and that positive effects may be more likely at relatively higher doses in this range. This study provides the basis for the design of future placebo-controlled studies of l-carnitine supplementation for cancer-related fatigue.     

Community Implementation of a Prehospital Spinal Immobilization Guideline

Objective: The purpose of this study was to qualitatively describe the underpinnings of the successful implementation of a collaborative prehospital spinal immobilization guideline throughout the emergency medical services (EMS) community in two counties in Colorado. We also describe lessons learned that may be beneficial to other communities considering similar initiatives. Methods: Qualitative data were collected from key informants who were directly involved in the implementation of a new prehospital spinal immobilization guideline among four community hospitals in two different hospital systems and the associated EMS providers within the two counties. We interviewed a purposively selected sample of emergency department (ED) physicians and other ED staff, hospital decision makers, EMS educators as well as fire department and EMS medical directors. Data were collected and reviewed until saturation was achieved. We conducted qualitative analysis to summarize and synthesize themes. Results: Ten key informants were interviewed, at which point saturation was achieved and several clear themes emerged. Participants described successful community-wide guideline implementation despite a history of competition, isolation, and conflict between the various EMS organizations and hospitals on past EMS and trauma initiatives. Factors related to success included the nearly universal perception that the initiative was “cutting edge” and thus an important paradigm shift in care for the community, as a whole. Participants reported the ability of community stakeholders to jointly assure a collaborative approach, characterized by intensive education for EMS personnel and others involved, and the ability of the community to together secure the new equipment required for success. Conclusions: Key informants described a convergence of factors as leading to the successful implementation of a prehospital spinal immobilization guideline. Lessons learned regarding how to overcome a tradition of competition and isolation to allow for success may be useful to other communities considering similar initiatives.     

Multicenter Evaluation of Prehospital Opioid Pain Management in Injured Children

Background: The National Association of Emergency Medical Services Physicians’ (NAEMSP) Position Statement on Prehospital Pain Management and the joint National Highway Traffic Safety Administration (NHTSA) and Emergency Medical Services for Children (EMSC) Evidence-based Guideline for Prehospital Analgesia in Trauma aim to improve the recognition, assessment, and treatment of prehospital pain. The impact of implementation of these guidelines on pain management in children by emergency medical services (EMS) agencies has not been assessed. Objective: Determine the change in frequency of documented pain severity assessment and opiate administration among injured pediatric patients in three EMS agencies after adoption of best practice recommendations. Methods: This is a retrospective study of children <18 years of age with a prehospital injury-related primary impression from three EMS agencies. Each agency independently implemented pain protocol changes which included adding the use of age-appropriate pain scales, decreasing the minimum age for opiate administration, and updating fentanyl dosing. We abstracted data from prehospital electronic patient records before and after changes to the pain management protocols. The primary outcomes were the frequency of administration of opioid analgesia and documentation of pain severity assessment as recorded in the prehospital patient care record. Results: A total of 3,597 injured children were transported prior to pain protocol changes and 3,743 children after changes. Opiate administration to eligible patients across study sites regardless of documentation of pain severity was 156/3,089 (5%) before protocol changes and 175/3,509 (5%) after (p = 0.97). Prior to protocol changes, 580 (18%) children had documented pain assessments and 430 (74%) had moderate-to-severe pain. After protocol changes, 644 (18%) patients had pain severity documented with 464 (72%) in moderate-to-severe pain. For all study agencies, pain severity was documented in 13%, 19%, and 22% of patient records both before and after protocol changes. There was a difference in intranasal fentanyl administration rates before (27%) and after (17%) protocol changes (p = 0.02). Conclusion: The proportion of injured children who receive prehospital opioid analgesia remains suboptimal despite implementation of best practice recommendations. Frequency of pain severity assessment of injured children is low. Intranasal fentanyl administration may be an underutilized modality of prehospital opiate administration.     

The ruptured Achilles tendon: operative and non-operative treatment options

The Achilles tendon is the strongest and thickest tendon in the human body. Like any other tendon in the body, however, it is susceptible to rupture. Many surgeons advocate early operative repair of the ruptured Achilles tendon, citing decreased re-rupture rates and improved functional outcome. Waiting for surgical repair for longer than one month may lead to inferior functional results postoperatively. Non-operative treatment has higher re-rupture rates as compared to surgically repaired tendons, but may be the treatment of choice in some patients. While for many years, patients were rigidly immobilized in a non-weightbearing cast for 6–8 weeks postoperatively, newer studies have shown excellent results with early weightbearing, and this is quickly becoming the standard of care amongst many physicians.     

Transdermal iontophoresis: modulation of electroosmosis by polypeptides

The objective of this research was to further evaluate the relative importance of electrorepulsion and electroosmosis to the mechanism of enhanced transport across the skin during iontophoresis. Specifically, the impact of iontophoresing into the skin positively and negatively charged polypeptides (poly-

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-lysines and poly-

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-glutamic acids, respectively) on the membrane's permselectivity, and hence on the quantity and direction of electroosmotic flow, was examined. Experiments were performed in vitro at pH 7.4 using conventional methodology; electroosmosis during the iontophoresis of the polypeptides into and across the skin was tracked in the usual way via the movement of the polar, uncharged, non-metabolizable marker, D-mannitol. Electrotransport of the cationic polypeptides attenuated electroosmotic flow in the normal anode-to-cathode direction; the degree of inhibition was correlated both with the initial concentration of poly-

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-lysine in the anodal chamber and with the molecular weight of the polypeptide employed (from 1 to 25 Kilodaltons). Iontophoresis of the anionic poly-

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-glutamic acids from the cathode provoked a slight increase in electroosmotic flow in the ‘reverse' direction (i.e. from the receptor phase beneath the skin towards the cathode chamber located on the epidermal side of the membrane); this effect, however, was much less dramatic than that produced in the opposite sense by the cationic polypeptides. The results suggest that driving large positively-charged polypeptide molecules into the skin leads to neutralization of the membrane's negativity, a subsequent loss of permselectivity and a concomitant attenuation of electroosmosis in the conventional anode-to-cathode direction. Presumably, the relatively poor iontophoretic permeability of these species (which becomes more and more evident with increasing molecular weight) results in a sufficiently important association of the polypeptide with the skin during the period of current passage. Much less significant effects are realized by the cathodal iontophoresis of poly-anions due to the difficulty of ‘pushing' negative ions into an already negatively-charged membrane.     

A simple aspiration test to determine the accuracy of oesophageal placement of fine-bore feeding tubes

Objective  To evaluate whether a simple aspiration test can be used to accurately confirm the correct placement of fine-bore feeding tubes in the oesophagus and prevent their inadvertent placement in the bronchial tree. Design  We conducted an ethically approved, randomised, blinded trial to assess the accuracy of a simple aspiration test to differentiate between oesophageal and tracheal placement. Setting  A tertiary referral cardiothoracic surgical unit. Patients and participants  Twenty patients under-going elective cardiac surgery. Intervention  Once anesthetised, a fine-bore feeding tube was inserted into the oesophagus or trachea and a researcher, blinded to the position, then performed the test. This involved attempted aspiration of ≥10 ml of air before and after insufflation of 10 ml of air and comparison with capnography, a test that has been shown to be highly sensitive and specific. Measurements and results  With this small number of patients, the test accurately differentiated between ten oesophageal and ten tracheal placements. Conclusions  A simple aspiration test could be a useful adjunct to prevent inadvertent bronchial placement of fine-bore feeding tubes. Careful attention must be paid to the technique to ensure that no false positives occur.     

Social, Achievement, and Control Dimensions of Personality-Life Event Vulnerability to Depression

This study investigated whether Sociotropy and the subscales of Autonomy (i.e., Perfectionistic/Self-critical, Need for Control, and Defensive Separation) would show differential patterns of vulnerability to dysphoria in both retrospective and prospective designs. Each of these scales showed a predicted pattern of association with life goals and impact ratings for negative events in a retrospective design. In a prospective design, the scales showed differential associations with goal obtainment and cognitive-affective responses to life events but did not predict follow-up dysphoria independently of baseline dysphoria. These results are discussed in terms of the multidimensionality of personality vulnerability and depressogenic negative life events along social, achievement, and control dimensions.

Psychopathy, Sexual Deviance, and Recidivism Among Sex Offenders

The relationships between psychopathy, sex offender type, sexual deviance, and recidivism were examined in 156 federally incarcerated sex offenders in a 10-year follow-up study. The rapists and mixed offenders demonstrated higher psychopathy scores than did the child molesters and incest offenders (total scores and Factor 2 scores on the Psychopathy Checklist--Revised [PCL-R]; R. D. Hare, 2003). Factor 1 scores were approximately the same in all groups. The PCL-R was a weak predictor of sexual recidivism but consistently predicted nonsexual violent recidivism and general recidivism (mainly via Factor 2). Sexual deviance measured by a structured rating scheme predicted sexual recidivism. Sexual deviance, so rated, was a stronger predictor of sexual recidivism than psychopathy but the two interacted significantly suggesting that psychopathy could potentiate sexual recidivism. Although psychopathy was a strong positive predictor of general nonsexual recidivism, sexual deviance was inversely related, and no interaction was observed between psychopathy, sexual deviance, and nonsexual recidivism.     

Assessing Eating Disorder Thoughts and Behaviors: The Development and Preliminary Evaluation of Two Questionnaires

This paper describes the development of two measures. The first is designed to assess eating disorder-related automatic thoughts; the second is designed to assess a wide range of eating disorder-related behaviors. Principal components analysis identified three dimensions of thoughts: positive thoughts about eating, negative thoughts about eating, and permissive thoughts. Principal components analysis also identified six dimensions of behavior related to: shape and weight, bingeing, dieting, food, eating, and overeating. Both measures possess promising psychometric properties, including good construct and criterion-related validity. Both successfully discriminated eating disorder patients from dieting and non-dieting groups. The two measures may be useful additions to those currently available to researchers (and clinicians) interested in eating disorders.