Randomized controlled trial of brief cognitive behaviour therapy versus treatment as usual in recurrent deliberate self-harm: the POPMACT study

BACKGROUND: We carried out a large randomized trial of a brief form of cognitive therapy, manual-assisted cognitive behaviour therapy (MACT) versus treatment as usual (TAU) for deliberate self-harm. METHOD: Patients presenting with recurrent deliberate self-harm in five centres were randomized to either MACT or (TAU) and followed up over 1 year. MACT patients received a booklet based on cognitive behaviour therapy (CBT) principles and were offered up to five plus two booster sessions of CBT from a therapist in the first 3 months of the study. Ratings of parasuicide risk, anxiety, depression, social functioning and global function, positive and negative thinking, and quality of life were measured at baseline and after 6 and 12 months. RESULTS: Four hundred and eighty patients were randomized. Sixty per cent of the MACT group had both the booklet and CBT sessions. There were seven suicides, five in the TAU group. The main outcome measure, the proportion of those repeating deliberate self-harm in the 12 months of the study, showed no significant difference between those treated with MACT (39%) and treatment as usual (46%) (OR 0.78, 95% CI 0.53 to 1.14, P=0.20). CONCLUSION: Brief cognitive behaviour therapy is of limited efficacy in reducing self-harm repetition, but the findings taken in conjunctin with the economic evaluation (Byford et al. 2003) indicate superiority of MACT over TAU in terms of cost and effectiveness combined.     

Oral ondansetron decreases vomiting after tonsillectomy in children

Vomiting is a common, unpleasant aftermath of tonsillectomy in children. Intraoperative intravenous ondansetron (OND) reduces vomiting after this operation. Our doubleblind, placebocontrolled, randomized investigation studied the effect of the oral form of OND on vomiting after outpatient tonsillectomy in children. We studied 233 healthy children age 2–14 yr undergoing elective tonsillectomy. Subjects were given placebo (PLAC) or OND 0.1 mg · kg^?1 rounded off to the nearest 2 mg one hr before surgery. Anaesthesia was induced with either propofol or halothane/N₂O. Vecuronium 0.1 mg · kg^?1 was administered at the discretion of the anaesthetist. Anaesthesia was maintained with halothane/N₂O, 50 μg · kg^?1 midazolam iv and 1–1.5 mg · kg^?1 codeine im. At the end of surgery, residual neuromuscular blockade was reversed with neostigmine and atropine. All episodes of inhospital emesis were recorded by nursing staff. Rescue antiemetics in the hospital were 1 mg · kg^?1 dimenhydrinate ivfor vomiting × 2 and 50 μg · kg^?1 droperidol iv for vomiting × 4. Parents kept a diary of emesis after discharge. Postoperative pain was treated with morphine, codeine and/or acetaminophen. The two groups were similar with respect to demographic data, induction technique and anaesthesia time. Oral OND (n = 109) reduced postoperative emesis from 54% to 39%, P < 0.05. This effect was most dramatic inhospital, where 10% of the OND-patients and 30% of the PLAC-group vomited, P < 0.05. The OND-subjects required fewer rescue antiemetics, 7% vs 17%, P < 0.05. In conclusion, oral ondansetron decreased the incidence of vomiting after outpatient tonsillectomy in children.     

The relevance of pulse repetition rate and radiant exposure to the neurophysiological effects of low-intensity laser (820 nm/pulsed wave) irradiation upon skin temperature and antidromic conduction latencies in the human median nerve

The effects of low-intensity near-infra-red laser irradiation (820 nm; 1.5 and 9.0 J cm^–2; pulsed at 12 Hz, 73 Hz and 5 kHz) upon peripheral neurophysiology and skin temperature were investigated using antidromic conduction studies in the human median nerve in vivo. Healthy human volunteers (n = 90) were recruited and allocated randomly to either a control group (n=10) or one of eight experimental groups (two radiant exposures, 1.5 J cm^–2 and 9.0 J cm^–2 at one of three pulse repetition rates, 12 Hz, 73 Hz or 5 kHz, in addition to a placebo group for each radiant exposure;n = 10 all groups). Analysis of variance (ANOVA) demonstrated a significant (p0.05) decrease in skin temperature following irradiation at the lowest radiant exposure (1.5 J cm^–2) combined with pulse repetition rates of 73 Hz and 5 kHz, with the greatest effect at 73 Hz. These changes in skin temperature were coupled with increases in negative peak latency (NPL); ie changes in NPL were inversely related to changes in skin temperature. However, in contrast to the authors' previous findings using continuous wave (CW) laser irradiation, differences in NPL were not found to be significant. These findings, therefore, provide little evidence of the neuro-physiological effects of low-intensity infra-red irradiation at the dosage levels and pulse repetition rates used here.     

Brain metabolic changes in major depressive disorder from pre- to post-treatment with paroxetine

Functional brain imaging studies of subjects with Major Depressive Disorder (MDD) have suggested that decreased dorsolateral (DLPFC) and increased ventrolateral (VLPFC) prefrontal cortical activity mediate the depressed state. Pre- to post-treatment studies indicate that these abnormalities normalize with successful treatment. We performed [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) scans on 16 outpatients with MDD before and after treatment with paroxetine (target dose = 40 mg/day). Regions of interest (ROIs) for this analysis were drawn by a rater blind to subject identity on the magnetic resonance image of each subject and transferred onto their coregistered PET scans. We hypothesized that DLPFC metabolism would increase, while ventral frontal metabolism [in the VLPFC, the orbitofrontal cortex (OFC), and the inferior frontal gyrus (IFG)] would decrease with successful treatment. Treatment response was defined as a decrease in the Hamilton Depression Rating Scale of > 50% and a Clinical Global Improvement Scale rating of 'much' or 'very much' improved. By these criteria, nine of the subjects were classified as treatment responders. These responders had significantly greater decreases in normalized VLPFC and OFC metabolism than did non-responders. There were no significant effects of treatment response on change in the DLPFC or IFG in this sample. However, there was a positive correlation between change in HAM-D scores and change in normalized IFG and VLPFC metabolism. There were no significant interactions with laterality. On pre-treatment scans, lower metabolism in the left ventral anterior cingulate gyrus was associated with better treatment response. These findings implicate ventral prefrontal-subcortical brain circuitry in the mediation of response to serotonin reuptake inhibitors in MDD.     

Lack of effect of combined low intensity laser therapy/phototherapy (CLILT) on delayed onset muscle soreness in humans

BACKGROUND AND OBJECTIVES: This study, which was approved by the University's Ethical committee, was conducted to investigate the effectiveness of Combined Low Intensity Laser Therapy/Phototherapy (CLILT) in alleviating the signs and symptoms of Delayed Onset Muscle Soreness (DOMS) over an 11-day period. STUDY DESIGN/MATERIALS AND METHODS: Thirty-six subjects (18 M: 18 F) were randomly allocated, under strictly controlled double-blind conditions, to one of three experimental conditions: Control, Placebo, and CLILT (660-950 nm; 11 J/cm2; pulsed at 73 Hz). DOMS was induced in a standardised fashion in the non-dominant elbow flexors using repeated eccentric contractions until exhaustion was reached. Subjects returned on five consecutive days, and two days during the following week, for treatment according to group, and assessment of outcome variables including range of motion, pain, and tenderness. RESULTS: While analysis of results using repeated measures and one factor ANOVA with post-hoc tests showed significant changes in all variables over time (P < 0.05) as a result of the induction procedure, there were no significant differences observed between groups. CONCLUSIONS: CLILT failed to show any beneficial treatment effect on DOMS, at least at the parameters used here. These results therefore provide no evidence for the claimed biostimulating effects of such therapy.     

5-Hydroxytryptamine4 receptors mediate relaxation of the rat oesophageal tunica muscularis mucosae

Summary The present study was designed to characterize an atypical 5-hydroxytryptamine (5-HT) receptor mediating relaxation of the rat oesophageal tunica muscularis mucosae. All experiments were performed under equilibrium conditions, using pargyline to inhibit the oxidative deamination of indoleamines, and cocaine and corticosterone to inhibit neuronal and extraneuronal uptake. Under these conditions 5-HT (0.3–1000 nmol/l) produced a concentration-dependent relaxation of carbachol-induced tension. The concentration-effect curve to 5-HT was unaffected by potent antagonists for 5-HT₁, 5-HT₂, 5-HT₃ and so called 5-HT_1P receptors (metergoline, methysergide, ketanserin, ondansetron, N-acetyl-5-hydroxytryptophyl-5-hydroxytryptophan amide), but was antagonized competitively by ICS 205–930 (pA₂ = 6.7). Responses to 5-HT were mimicked by other indoleamines and substituted benzamides with the following order of potency: 5-HT 5-methoxytryptamine > cisapride = -methyl-5-HT = (S)-zacopride = renzapride > (RS)-zacopride > 5-carboxamido-tryptamine = metoclopramide = (R)-zacopride > tryptamine > 2-methyl-5-HT. ICS 205–930 afforded similar pA₂ values (6.0–6.7) against each agonist, indicating a common site of action. Concentration-effect curves to 5-HT were not affected by tetrodotoxin or indomethacin, sugesting that 5-HT-induced relaxation of the tunica muscularis mucosae was mediated via a postjunctional receptor, independent of endogenous prostanoids. The pharmacological profile of the 5-HT receptor in the rat oesophageal tunica muscularis mucosae correlates well with the 5-HT₄ receptor characterized recently in both the CNS and gastro-intestinal tract. Send offprint requests to D. E. Clarke at the above address     

Psychiatry Resident and Medical Student Perspectives on ECT: Influence of Exposure and Education

We surveyed medical students doing the required psychiatry clerkship at our hospital and first-year psychiatry residents in our residency training program for their attitudes, knowledge, and opinions about electroconvulsive therapy (ECT) before and after their inpatient rotations. The students' knowledge was lower and their attitudes more negative toward ECT than those of residents at baseline. Upon completion of the rotation, students and residents had more knowledge and highly positive attitudes about ECT and stated that they would undergo ECT if it were recommended. Willingness to undergo ECT if it were recommended correlated with the knowledge measures of ECT.     

Transport of fluid and macromolecules in tumors. IV. A microscopic model of the perivascular distribution

The therapeutic efficacy of various genetically engineered macromolecules is determined by their delivery and distribution in tumors. We have recently developed mathematical models which describe the interstitial velocity, pressure, and concentration profiles of macromolecules over the length scale of a solid tumor (Baxter and Jain, Microvas. Res. 1989, 1990, 1991). Nonspecific and specific antibodies and antibody fragments were chosen as typical macromolecules. The focus of the present investigation was microscopic transport, i.e., the distribution of pressure and solutes around individual blood vessels. Analytical solutions were obtained for interstitial velocities and pressures, while the concentration profiles were calculated numerically using the finite element method. The microscopic model describes flow patterns around an individual blood vessel in an infinite medium and concentration profiles around a single blood vessel in a network of capillaries. Our analysis is novel in that it incorporates interstitial convection, asymmetric filtration, and transcapillary convection to describe interstitial transport in tumors. The purpose of this model was to determine the effect of extravascular binding and interstitial convection on the distribution of macromolecules on a microscopic scale and to test the continuum hypothesis assumed in our previously published macroscopic models. An approximate one-dimensional model was compared with a more accurate two-dimensional model. The results of our microscopic model confirm that the continuum hypothesis used in our previous macroscopic model is reasonable. On a microscopic length scale diffusion is dominant, and short range distortions in the flow field do not significantly affect the penetration of macromolecules into the tissue. In addition, our model confirms the results of Fujimori et al. (Cancer Res., 1989) concerning a "binding site barrier." The implications of our results for cancer therapy are also discussed.