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SUMMARY A series of fifty-one cases of lumbo-sacral spondylolisthesis under the age of thirty years were followed up for a minimum period of one year. The overall progression rate in this series was 24%, but more significantly, the incidence of progression in adolescence was 38%. Furthermore, there was a marked difference in the incidence of progression in the dysplastic type (32%) compared with the isthmic type (4%). Radiological studies showed that adolescent progression occurred concurrently with significant structural changes in both the 5th lumbar vertebra and the sacrum. It was felt that the loss of support of the posterior vertebral complex in dysplastic spondylolisthesis resulted in an interference in the vertebral growth once displacement exceeded 25%, demonstrating that progression may occur before a fusion becomes sound. Late progression was not accompanied by structural changes, and was due to a loss of posterior ligamentous and disc integrity. [ABSTRACT FROM AUTHOR]

Background: Migraine is a common neurological problem associated with the highest burden amongst neurological conditions in terms of years lived with disability. Medications can be used as prophylaxis or rescue medicines, but are costly and not always effective. A range of psychological interventions have been developed to manage migraine., Objectives: The objective was to evaluate the efficacy and adverse events of psychological therapies for the prevention of migraine in adults., Search Methods: We searched CENTRAL, MEDLINE, Embase, PsycINFO and CINAHL from their inception until July 2018, and trials registries in the UK, USA, Australia and New Zealand for randomised controlled trials of any psychological intervention for adults with migraine., Selection Criteria: We included randomised controlled trials (RCTs) of a psychological therapy for people with chronic or episodic migraine, with or without aura. Interventions could be compared to another active treatment (psychological or medical), an attention-placebo (e.g. supportive counselling) or other placebo, routine care, or waiting-list control. We excluded studies where fewer than 15 participants completed each arm., Data Collection and Analysis: We extracted study characteristics and outcome data at post-treatment and the longest available follow-up. We analysed intervention versus control comparisons for the primary outcome of migraine frequency. We measured migraine frequency using days with migraines or number of migraine attacks measured in the four weeks after treatment. In addition, we analysed the following secondary outcomes: responder rate (the proportion of participants with a 50% reduction in migraine frequency between the four weeks prior to and the four weeks after treatment); migraine intensity; migraine duration; migraine medication usage; mood; quality of life; migraine-related disability; and proportion of participants reporting adverse events during the treatment. We included these variables, where available, at follow-up, the timing of which varied between the studies. We used the GRADE approach to judge the quality of the evidence., Main Results: We found 21 RCTs including 2482 participants with migraine, and we extracted meta-analytic data from 14 of these studies. The majority of studies recruited participants through advertisements, included participants with migraine according to the International Classification of Headache Disorders (ICHD) criteria and those with and without aura. Most intervention arms were a form of behavioural or cognitive-behavioural therapy. The majority of comparator arms were no treatment, routine care or waiting list. Interventions varied from one 20-minute session to 14 hours of intervention. No study had unequivocally low risk of bias; all had at least one domain at high risk of bias, and 20 had two to five domains at high risk. Reporting of randomisation procedures and allocation concealment were at high or unclear risk of bias. We downgraded the quality of evidence for outcomes to very low, due to very serious limitations in study quality and imprecision. Reporting in trials was poor; we found no preregistrations stipulating the outcomes, or demonstrating equivalent expectations between groups. Few studies reported our outcomes of interest, most only reported outcomes post treatment; follow-up data were sparse.Post-treatment effectsWe found no evidence of an effect of psychological interventions for migraine frequency in number of migraines or days with migraine (standardised mean difference (SMD) -0.02, 95% confidence interval (CI) -0.17 to 0.13; 4 studies, 681 participants; very low-quality evidence).The responder rate (proportion of participants with migraine frequency reduction of more than 50%) was greater for those who received a psychological intervention compared to control: 101/186 participants (54%) with psychological therapy; 37/152 participants (24%) with control (risk ratio (RR) 2.21, 95% CI 1.63 to 2.98; 4 studies, 338 participants; very low-quality evidence). We found no effect of psychological therapies on migraine intensity (SMD -0.13, 95% CI -0.28 to 0.02; 4 studies, 685 participants). There were no data for migraine duration (hours of migraine per day). There was no effect on migraine medication usage (SMD -0.06, 95% CI -0.35 to 0.24; 2 studies, 483 participants), mood (mean difference (MD) 0.08, 95% CI -0.33 to 0.49; 4 studies, 432 participants), quality of life (SMD -0.02, 95% CI -0.30 to 0.26; 4 studies, 565 participants), or migraine-related disability (SMD -0.67, 95% CI -1.34 to 0.00; 6 studies, 952 participants). The proportion of participants reporting adverse events did not differ between those receiving psychological treatment (9/107; 8%) and control (30/101; 30%) (RR 0.16, 95% CI 0.00 to 7.85; 2 studies, 208 participants). Only two studies reported adverse events and so we were unable to draw any conclusions.We rated evidence from all studies as very low quality.Follow-upOnly four studies reported any follow-up data. Follow-ups ranged from four months following intervention to 11 months following intervention. There was no evidence of an effect on any outcomes at follow-up (very low-quality evidence)., Authors' Conclusions: This review identified 21 studies of psychological interventions for the management of migraine. We did not find evidence that psychological interventions affected migraine frequency, a result based on four studies of primarily brief treatments. Those who received psychological interventions were twice as likely to be classified as responders in the short term, but this was based on very low-quality evidence and there was no evidence of an effect of psychological intervention compared to control at follow-up. There was no evidence of an effect of psychological interventions on medication usage, mood, migraine-related disability or quality of life. There was no evidence of an effect of psychological interventions on migraine frequency in the short-term or long-term. In terms of adverse events, we were unable to draw conclusions as there was insufficient evidence. High and unclear risk of bias in study design and reporting, small numbers of participants, performance and detection bias meant that we rated all evidence as very low quality. Therefore, we conclude that there is an absence of high-quality evidence to determine whether psychological interventions are effective in managing migraine in adults and we are uncertain whether there is any difference between psychological therapies and controls.

DDD-028 (4), a novel pentacyclic pyridoindolobenzazepine derivative was evaluated in vitro for receptor binding affinity and in vivo for analgesic activity using rodent models of neuropathic and inflammatory pain. DDD-028 does not bind to opioid, cannabinoid, dopamine, or histamine receptors. DDD-028 is very active even at the low oral dose of 1-5 mg/kg in both neuropathic, (spinal nerve ligation and chronic constriction injury) and inflammatory (Complete Freund's Adjuvant Induced) models of pain. DDD-028 appears to be about 6-fold more potent than pregabalin and indomethacin. Visual observation of all the animals used in these studies indicated that DDD-028 is well tolerated without any sedation. Thus, DDD-028 seems to be a promising candidate for the treatment of neuropathic and inflammatory pain without the possible side effects or abuse potential associated with opioid or cannabinoid activities., (Copyright © 2014 Elsevier Ltd. All rights reserved.)