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Functional gastrointestinal disorders are common and costly to the healthcare system. In the Multidisciplinary Treatment of Functional Gastrointestinal Disorders study, we demonstrated that multidisciplinary care resulted in superior clinical and cost outcomes, when compared with standard gastroenterologist-only care at end of treatment. In this study we evaluate the longer-term outcomes. In a single-center, pragmatic trial patients with Rome IV criteria-defined functional gastrointestinal disorders were randomized 1:2 to a gastroenterologist-only standard care vs a multidisciplinary clinic comprising gastroenterologists, dietitians, gut hypnotherapists, psychiatrists, and biofeedback physiotherapists. Outcomes in this study were assessed 12 months after the end of treatment. Global symptom improvement was assessed by using a 5-point Likert scale. Symptoms, specific disorder status, psychological state, quality of life, and cost were additional outcomes. A modified intention-to-treat analysis was performed. Of 188 randomized patients, 143 (46 standard care, 97 multidisciplinary) formed the longer-term modified intention-to-treat analysis. Sixty-two percent of multidisciplinary clinic patients saw allied clinicians. Sixty-five percent (30/46) standard care versus 76% (74/97) multidisciplinary clinic patients achieved global symptom improvement 12 months after end of treatment (P =.17), whereas 20% (9/46) versus 37% (36/97) rated their symptoms as "5/5 much better" (P =.04). A ≥50-point reduction in Irritable Bowel Syndrome Severity Scoring System occurred in 38% versus 66% (P =.02), respectively, for irritable bowel syndrome patients. Anxiety and depression were greater in the standard care than multidisciplinary clinic (12 vs 10, P =.19), and quality of life was lower in standard care than the multidisciplinary clinic (0.75 vs 0.77, P =·.03). An incremental cost-effectivness ratio found that for every additional 3555AUD spent in the multidisciplinary clinic, a further quality-adjusted life year was gained. Twelve months after the completion of treatment, integrated multidisciplinary clinical care achieved a greater proportion of patients with improvement of symptoms, psychological state, quality of life, and cost, compared with gastroenterologist-only care. Clinical trials.gov: number NCT03078634 [Display omitted] [ABSTRACT FROM AUTHOR]

Summary: Early life stress causes long-lasting effects on the limbic system that may be relevant to the development of mesial temporal lobe epilepsy (MTLE) and its associated psychopathology. Recent studies in rats suggest that maternal separation (MS), a model of early life stress, confers enduring vulnerability to amygdala kindling limbic epileptogenesis. However, the mechanisms underlying this remain unknown. Here, we tested whether hypothalamic-pituitary-adrenal (HPA) axis hyper-reactivity induced by MS – specifically the excessive secretion of corticosterone following a seizure – was involved in this vulnerability. In adult female rats subjected to MS from postnatal days 2–14, seizure-induced corticosterone responses were significantly augmented and prolonged for at least two hours post-seizure, compared to control early-handled (EH) rats. This was accompanied by reduced seizure threshold (p <0.05) and increased vulnerability to the kindling-induced progression of seizure duration (p <0.05) in MS rats. Pre-seizure treatment with the corticosterone synthesis inhibitor, metyrapone (MET) (50mg/kgsc) effectively blocked seizure-induced corticosterone responses. When delivered throughout kindling, MET treatment also reversed the MS-induced reduction in seizure threshold and the lengthened seizure duration back to levels of EH rats. These observations suggest that adverse early life environments induce a vulnerability to kindling epileptogenesis mediated by HPA axis hyper-reactivity, which could have relevance for the pathogenesis of MTLE. [Copyright &y& Elsevier]

Objectives: A large body of research has demonstrated that patient factors are strong predictors of recovery from surgery. Mind-body therapies are increasingly targeted at pre-operative psychological factors. The objective of this paper was to evaluate the efficacy of pre-operative mind-body based interventions on post-operative outcome measures amongst elective surgical patients. Methods: A systematic review of the published literature was conducted using the electronic databases MEDLINE, CINAHL and PsychINFO. Randomised controlled trials (RCTs) with a prospective before-after surgery design were included. Results: Twenty studies involving 1297 patients were included. Mind-body therapies were categorised into relaxation, guided imagery and hypnotic interventions. The majority of studies did not adequately account for the risk of bias thus undermining the quality of the evidence. Relaxation was assessed in eight studies, with partial support for improvements in psychological well-being measures, and a lack of evidence for beneficial effects for analgesic intake and length of hospital stay. Guided imagery was examined in eight studies, with strong evidence for improvements in psychological well-being measures and moderate support for the efficacy of reducing analgesic intake. Hypnosis was investigated in four studies, with partial support for improvements in psychological well-being measures. Evidence for the effect of mind-body therapies on physiological indices was limited, with minimal effects on vital signs, and inconsistent changes in endocrine measures reported. Conclusions: This review demonstrated that the quality of evidence for the efficacy of mind-body therapies for improving post-surgical outcomes is limited. Recommendations have been made for future RCTs. [ABSTRACT FROM AUTHOR]

Summary: Psychiatric disorders associated with elevated stress levels, such as depression, are present in many epilepsy patients, including those with mesial Temporal Lobe Epilepsy (mTLE). Evidence suggests that these psychiatric disorders can predate the onset of epilepsy, suggesting a causal/contributory role. Prolonged exposure to elevated corticosterone, used as a model of chronic stress/depression, accelerates limbic epileptogenesis in the amygdala kindling model. The current study examined whether exposure to repeated stress could similarly accelerate experimental epileptogenesis. Female adult non-epileptic Wistar rats were implanted with a bipolar electrode into the left amygdala, and were randomly assigned into stressed (n =18) or non-stressed (n =19) groups. Rats underwent conventional amygdala kindling (two electrical stimulations per day) until 5 Class V seizures had been experienced (‘the fully kindled state’). Stressed rats were exposed to 30min restraint immediately prior to each kindling stimulation, whereas non-stressed rats received control handling. Restraint stress increased circulating corticosterone levels (pre-stress: 122±17ng/ml; post-stress: 632±33ng/ml), with no habituation observed over the experiment. Stressed rats reached the ‘fully kindled state’ in significantly fewer stimulations than non-stressed rats (21±1 vs 33±3 stimulations; p =0.022; ANOVA), indicative of a vulnerability to epileptogenesis. Further, seizure durations were significantly longer in stressed rats (p <0.001; ANOVA). These data demonstrate that exposure to repeated experimental stress accelerates the development of limbic epileptogenesis, an effect which may be related to elevated corticosterone levels. This may have implications for understanding the effects of chronic stress and depression in disease onset and progression of mTLE in humans. [ABSTRACT FROM AUTHOR]

Summary: We have previously demonstrated that low-dose corticosterone (CS) administration, used as a model of the effect of chronic stress, accelerates epileptogenesis in the electrical amygdala kindling rat model of temporal lobe epilepsy (TLE). This current study examined the relative contributions to this effect of mineralocorticoid (MR) and glucocorticoid (GR) subtypes of glucocorticoid receptors. Female non-epileptic wistar rats 10–13 weeks of age were implanted with a bipolar electrode into the left amygdala. Five treatment groups were subjected to rapid amygdala kindling: water-control (n=9), CS treated (6mg/100ml added to drinking water; n=9), CS+spironolactone (MR antagonist, 50mg/kgsc; n=9), CS+mifepristone (GR antagonist, 25mg/kgsc; n=9), and CS+both antagonists (n=7). Rats were injected with vehicle or the relevant antagonist twice daily for the entire kindling period. Experimental groups differed significantly in the number of stimulations required to reach the ‘fully kindled state’ (Racine, 1972) ANOVA, F (4,38)=2.73, p=0.04). Amygdala kindling was accelerated in the CS-treated group compared with water controls (mean stimulations for full kindling: 45.2 vs. 86.5, p<0.01). This acceleration was inhibited by both the MR and GR antagonist treatments (mean stimulations: 69.6 and 70.4, p=0.04 and 0.04 vs. CS group, respectively), with the kindling rates in these groups not significantly different from water-treated subjects (p=0.26 and 0.29, respectively). The kindling rates in the MR and GR antagonist treatment groups did not significantly differ from each other (p=0.93), nor from the combined treatment group (mean stimulations: 62.8, p=0.59 and 0.54, respectively). This study demonstrates that activation of both high-affinity (MR) and low-affinity (GR) glucocorticoid receptors are involved in mediating CS-induced acceleration of amygdala kindling epileptogenesis. [Copyright &y& Elsevier]