FORWARDS-1: an adaptive, single-blind, placebo-controlled ascending dose study of acute baclofen on safety parameters in opioid dependence during methadone-maintenance treatment-a pharmacokinetic-pharmacodynamic study.

BACKGROUND: Treatment of opiate addiction with opiate substitution treatment (e.g. methadone) is beneficial. However, some individuals desire or would benefit from abstinence but there are limited options to attenuate problems with opiate withdrawal. Preclinical and preliminary clinical evidence suggests that the GABA-B agonist, baclofen, has the desired properties to facilitate opiate detoxification and prevent relapse. This study aims to understand whether there are any safety issues in administering baclofen to opioid-dependent individuals receiving methadone. METHODS: Opiate-dependent individuals (DSM-5 severe opioid use disorder) maintained on methadone will be recruited from addiction services in northwest London (NHS and third sector providers). Participants will be medically healthy with no severe chronic obstructive pulmonary disease or type 2 respiratory failure, no current dependence on other substances (excluding nicotine), no current severe DSM-5 psychiatric disorders, and no contraindications for baclofen or 4800 IU vitamin D (placebo). Eligible participants will be randomised in a 3:1 ratio to receive baclofen or placebo in an adaptive, single-blind, ascending dose design. A Bayesian dose-escalation model will inform the baclofen dose (10, 30, 60, or 90 mg) based on the incidence of 'dose-limiting toxicity' (DLT) events and participant-specific methadone dose. A range of respiratory, cardiovascular, and sedative measures including the National Early Warning Score (NEWS2) and Glasgow Coma Scale will determine DLT. On the experimental day, participants will consume their usual daily dose of methadone followed by an acute dose of baclofen or placebo (vitamin D3) ~ 1 h later. Measures including oxygen saturation, transcutaneous CO2, respiratory rate, QTc interval, subjective effects (sedation, drug liking, craving), plasma levels (baclofen, methadone), and adverse events will be obtained using validated questionnaires and examinations periodically for 5 h after dosing. DISCUSSION: Study outcomes will determine what dose of baclofen is safe to prescribe to those receiving methadone, to inform a subsequent proof-of-concept trial of the efficacy baclofen to facilitate opiate detoxification. To proceed, the minimum acceptable dose is 30 mg of baclofen in patients receiving ≤ 60 mg/day methadone based on the clinical experience of baclofen's use in alcoholism and guidelines for the management of opiate dependence. TRIAL REGISTRATION: Clinicaltrials.gov NCT05161351. Registered on 16 December 2021.

Local Adaptation in Marine Foundation Species at Microgeographic Scales.

AbstractNearshore foundation species in coastal and estuarine systems (e.g., salt marsh grasses, mangroves, seagrasses, corals) drive the ecological functions of ecosystems and entire biomes by creating physical structure that alters local abiotic conditions and influences species interactions and composition. The resilience of foundation species and the ecosystem functions they provide depends on their phenotypic and genetic responses to spatial and temporal shifts in environmental conditions. In this review, we explore what is known about the causes and consequences of adaptive genetic differentiation in marine foundation species over spatial scales shorter than dispersal capabilities (i.e., microgeographic scales). We describe the strength of coupling field and laboratory experiments with population genetic techniques to illuminate patterns of local adaptation, and we illustrate this approach by using several foundation species. Among the major themes that emerge from our review include (1) adaptive differentiation of marine foundation species repeatedly evolves along vertical (i.e., elevation or depth) gradients, and (2) mating system and phenology may facilitate this differentiation. Microgeographic adaptation is an understudied mechanism potentially underpinning the resilience of many sessile marine species, and this evolutionary mechanism likely has particularly important consequences for the ecosystem functions provided by foundation species.

Effects of naltrexone are influenced by childhood adversity during negative emotional processing in addiction recovery.

Naltrexone is an opioid receptor antagonist used in the management of alcohol dependence. Although the endogenous opioid system has been implicated in emotion regulation, the effects of mu-opioid receptor blockade on brain systems underlying negative emotional processing are not clear in addiction. Individuals meeting criteria for alcohol dependence alone (n=18, alcohol) and in combination with cocaine and/or opioid dependence (n=21, alcohol/drugs) and healthy individuals without a history of alcohol or drug dependence (n=21) were recruited. Participants were alcohol and drug abstinent before entered into this double-blind, placebo-controlled, randomized, crossover study. Functional magnetic resonance imaging was used to investigate brain response while viewing aversive and neutral images relative to baseline on 50 mg of naltrexone and placebo. We found that naltrexone modulated task-related activation in the medial prefrontal cortex and functional connectivity between the anterior cingulate cortex and the hippocampus as a function of childhood adversity (for aversive versus neutral images) in all groups. Furthermore, there was a group-by-treatment-by-condition interaction in the right amygdala, which was mainly driven by a normalization of response for aversive relative to neutral images under naltrexone in the alcohol/drugs group. We conclude that early childhood adversity is one environmental factor that influences pharmacological response to naltrexone. Pharmacotherapy with naltrexone may also have some ameliorative effects on negative emotional processing in combined alcohol and drug dependence, possibly due to alterations in endogenous opioid transmission or the kappa-opioid receptor antagonist actions of naltrexone.

Decreased hippocampal translocator protein (18 kDa) expression in alcohol dependence: a [11C]PBR28 PET study.

Repeated withdrawal from alcohol is clinically associated with progressive cognitive impairment. Microglial activation occurring during pre-clinical models of alcohol withdrawal is associated with learning deficits. We investigated whether there was microglial activation in recently detoxified alcohol-dependent patients (ADP), using [11C]PBR28 positron emission tomography (PET), selective for the 18kDa translocator protein (TSPO) highly expressed in activated microglia and astrocytes. We investigated the relationship between microglial activation and cognitive performance. Twenty healthy control (HC) subjects (45±13; M:F 14:6) and nine ADP (45±6, M:F 9:0) were evaluated. Dynamic PET data were acquired for 90 min following an injection of 331±15 MBq [11C]PBR28. Regional volumes of distribution (VT) for regions of interest (ROIs) identified a priori were estimated using a two-tissue compartmental model with metabolite-corrected arterial plasma input function. ADP had an ~20% lower [11C]PBR28 VT, in the hippocampus (F(1,24) 5.694; P=0.025), but no difference in VT in other ROIs. Hippocampal [11C]PBR28 VT was positively correlated with verbal memory performance in a combined group of HC and ADP (r=0.720, P<0.001), an effect seen in HC alone (r=0.738; P=0.001) but not in ADP. We did not find evidence for increased microglial activation in ADP, as seen pre-clinically. Instead, our findings suggest lower glial density or an altered activation state with lower TSPO expression. The correlation between verbal memory and [11C]PBR28 VT, raises the possibility that abnormalities of glial function may contribute to cognitive impairment in ADP.

Temporal stability in patterns of genetic diversity and structure of a marine foundation species (Zostera marina).

Genetic diversity and population structure reflect complex interactions among a diverse set of processes that may vary temporally, limiting their potential to predict ecological and evolutionary outcomes. Yet, the stability of these patterns is rarely tested. We resampled eelgrass (Zostera marina) meadows from published studies to determine variability in genetic diversity and structure within and between meadows over 5-12 years. The meadows sampled (San Francisco, Tomales and Bodega Bays in California and the Virginia coastal bays) represent a range of life histories (annual vs perennial), age (well-established vs restored) and environments (rural vs urbanized). In all of these systems, neither diversity nor differentiation (FST) changed over time. Differences among tidal heights within Bodega Bay were also remarkably consistent, with the high intertidal being more diverse than the subtidal, and tidal height differentiation being modest but significant at both time points. Historical studies used only a few microsatellite loci; therefore, our temporal comparisons were based on 4-5 loci. However, analysis of the current data using a set of 12 loci show that 4-5 loci are sufficient to describe diversity and differentiation patterns in this system. This temporal consistency was not because of the resampling of large clones, underscoring the feasibility and relevance of understanding drivers of the differences. Because seagrasses are declining at rapid rates, restoration and conservation are increasingly a coastal management priority. Our results argue that surveys of eelgrass genetic structure and diversity at decadal scales can provide accurate depictions of populations, increasing the utility of published genetic data for restoration and designing networks of reserves.

Lifestyle interventions for type 2 diabetes prevention in women with prior gestational diabetes: A systematic review and meta-analysis of behavioural, anthropometric and metabolic outcomes.

PURPOSE: To systematically review lifestyle interventions for women with prior Gestational Diabetes Mellitus (GDM) to report study characteristics, intervention design and study quality and explore changes in 1) diet, physical activity and sedentary behaviour; 2) anthropometric outcomes and; 3) glycaemic control and diabetes risk. METHODS: Databases (Web of Science, CCRCT, EMBASE and Science DIRECT) were searched (1980 to April 2014) using keywords for controlled or pre-post design trials of lifestyle intervention targeting women with previous GDM reporting at least one behavioural, anthropometric or diabetes outcome. Selected studies were narratively synthesized with anthropometric and glycaemic outcomes synthesized using meta-analysis. RESULTS: Three of 13 included studies were rated as low bias risk. Recruitment rates were poor but study retention good. Six of 11 studies reporting on physical activity reported favourable intervention effects. All six studies reporting on diet reported favourable intervention effects. In meta-analysis, significant weight-loss was attributable to one Chinese population study (WMD = - 1.06 kg (95% CI = - 1.68, - 0.44)). Lifestyle interventions did not change fasting blood glucose (WMD = - 0.05 mmol/L, 95% CI = - 0.21, 0.11) or type 2 diabetes risk. CONCLUSIONS: Lack of methodologically robust trials gives limited evidence for the success of lifestyle interventions in women with prior GDM. Recruitment into trials is challenging.

Matching of feedback inhibition with excitation ensures fidelity of information flow in the anterior piriform cortex.

Odor-evoked responses in mitral cells of the olfactory bulb are characterized by prolonged patterns of action potential (spike) activity. If downstream neurons are to respond to each spike in these patterns, the duration of the excitatory response to one spike should be limited, enabling cells to respond to subsequent spikes. To test for such mechanisms, we performed patch-clamp recordings in slices of the mouse anterior piriform cortex. Mitral cell axons in the lateral olfactory tract (LOT) were stimulated electrically at different intensities and with various frequency patterns to mimic changing input conditions that the piriform cortex likely encounters in vivo. We found with cell-attached measurements that superficial pyramidal (SP) cells in layer 2 consistently responded to LOT stimulation across conditions with a limited number (1-2) of spikes per stimulus pulse. The key synaptic feature accounting for the limited spike number appeared to be somatic inhibition derived from layer 3 fast-spiking cells. This inhibition tracked the timing of the first spike in SP cells across conditions, which naturally limited the spike number to 1-2. These response features to LOT stimulation were, moreover, not unique to SP cells, also occurring in a population of fluorescently labeled interneurons in glutamic acid decarboxylase 65-eGFP mice. That these different cortical cells respond to incoming inputs with 1-2 spikes per stimulus may be especially critical for relaying bulbar information contained in synchronized oscillations at beta (15-30Hz) or gamma (30-80Hz) frequencies.

Assessment of point-of-care measurement of international normalised ratio using the CoaguChek XS Plus system in the setting of acute ischaemic stroke.

BACKGROUND AND AIMS: Thrombolysis with alteplase (recombinant tissue plasminogen activator) is accepted hyperacute therapy for acute ischaemic stroke. Clotting must be normal before this can be administered safely. Laboratory testing of international normalised ratio (INR) takes 30-60 min, which can significantly delay administration of recombinant tissue plasminogen activator. Previous studies have suggested that point-of-care testing is useful in patients presenting with stroke and improves door-to-needle time. We performed a prospective study of point-of-care testing in patients presenting with acute ischaemic stroke. METHODS: Fifty patients were entered into the study to compare point-of-care testing using the CoaguChek XS system with laboratory testing of INR. RESULTS: Point-of-care testing correlated well with laboratory levels (R = 0.93, P < 0.0001). The standard deviation of difference between the two was 0.115. Overall, point-of-care testing tended to underestimate INR slightly, meaning that an INR value of 1.1 or less was required to be 95% certain that the laboratory value was 1.3 or below. Simultaneous testing using blood from a syringe was more consistent with laboratory results than testing capillary blood through finger prick. CONCLUSION: Point-of-care INR testing correlates well with laboratory values. The results in this study mostly relate to values in the normal range. We suggest that it can be used to try to shorten door-to-needle time.

BAP updated guidelines: evidence-based guidelines for the pharmacological management of substance abuse, harmful use, addiction and comorbidity: recommendations from BAP.

The British Association for Psychopharmacology guidelines for the treatment of substance abuse, harmful use, addiction and comorbidity with psychiatric disorders primarily focus on their pharmacological management. They are based explicitly on the available evidence and presented as recommendations to aid clinical decision making for practitioners alongside a detailed review of the evidence. A consensus meeting, involving experts in the treatment of these disorders, reviewed key areas and considered the strength of the evidence and clinical implications. The guidelines were drawn up after feedback from participants. The guidelines primarily cover the pharmacological management of withdrawal, short- and long-term substitution, maintenance of abstinence and prevention of complications, where appropriate, for substance abuse or harmful use or addiction as well management in pregnancy, comorbidity with psychiatric disorders and in younger and older people.

Central noradrenergic responsiveness to a clonidine challenge in Generalized Anxiety Disorder: a Single Photon Emission Computed Tomography study.

Generalized Anxiety Disorder (GAD) may involve hypo-responsiveness of noradrenaline a2 receptors. To test this hypothesis, we used (99m)Tc-hexa-methyl-propylene-amine-oxime (HMPAO) Single Photon Emission Computed Tomography to measure regional cerebral perfusion in patients with untreated GAD, venlafaxine-treated patients and healthy controls during word generation before and after clonidine. Concurrent psychological and physiological measures supported noradrenergic hypofunction in GAD in some cases. A single-day split-dose technique was used. Images were processed using SPM5 (Institute of Neurology). Factorial analysis revealed no significant results. Exploratory analyses were done. Regional perfusion during verbal fluency differed by group pre-clonidine. Compared with healthy controls, patients with untreated GAD displayed increased perfusion in the left Broca's area and left occipitotemporal region. Treated GAD patients displayed increased cerebellar perfusion bilaterally. Clonidine was associated with different changes in cerebral perfusion in each group. Increases were seen in the right supra-marginal gyrus in healthy subjects, in the left pre-central gyrus in treated GAD patients and in the right cerebellum and middle frontal gyrus in untreated GAD patients. Despite these differences, the findings were not consistent with a noradrenergic hypo-responsiveness hypothesis, as the treated group showed a different pattern of response rather than a normalization of response.

A pilot study of the effectiveness of D-cycloserine during cue-exposure therapy in abstinent alcohol-dependent subjects.

RATIONALE: Cue-exposure therapy (CET) has been advocated as a potentially effective treatment of addictive behaviours. Strategies that enhance learning may improve the outcome of CET. D-cycloserine (DCS), a partial N-methyl-D-aspartate receptor agonist, has been shown to facilitate extinction of learned fear in rats and augment exposure-based treatment in some anxiety disorders in man. OBJECTIVE: This double-blind placebo-controlled pilot study used a cue-exposure paradigm, salient for an individual's alcohol drinking, to see if DCS would reduce cue-reactivity compared with placebo. METHODS: Sixteen abstinent, alcohol-dependent individuals were randomised to receive either a single-dose (250 mg) DCS or placebo before CET sessions, separated by at least 1 week. Subjective responses were assessed using the Alcohol Urge Questionnaire (AUQ) and visual analogue scales. Cardiovascular responses were assessed using Finapres©. RESULTS: The cue-exposure paradigm significantly increased craving assessed with the AUQ during the first session. In subsequent sessions, the degree of craving was reduced. However, no significant difference was seen between the DCS and placebo groups in any outcome measure. The variability of responses between individuals was great with more than half the groups reporting no or very small changes in AUQ scores. CONCLUSION: This is the first human study to our knowledge to assess the efficacy of DCS in facilitating CET in alcohol dependence. The high proportion of subjects with little or no response to cue-exposure would make any effect of DCS very difficult to detect. It is important that future studies carefully consider the criteria for inclusion.

The role of central noradrenergic dysregulation in anxiety disorders: evidence from clinical studies.

The nature of the noradrenergic dysregulation in clinical anxiety disorders remains unclear. In panic disorder, the predominant view has been that central noradrenergic neuronal networks and/or the sympathetic nervous system was normal in patients at rest, but hyper-reactive to specific stimuli, for example carbon dioxide. These ideas have been extended to other anxiety disorders, which share with panic disorder characteristic subjective anxiety and physiological symptoms of excess sympathetic activity. For example, Generalized Anxiety Disorder is characterized by chronic free-floating anxiety, muscle tension, palpitation and insomnia. It has been proposed that there is chronic central hypersecretion of noradrenaline in Generalized Anxiety Disorder, with consequent hyporesponsiveness of central post-synaptic receptors. With regards to other disorders, it has been suggested that there is noradrenergic involvement or derangement, but a more specific hypothesis has not been enunciated. This paper reviews the evidence for noradrenergic dysfunction in anxiety disorders, derived from indirect measures of noradrenergic function in clinical populations.

Noradrenergic function in generalized anxiety disorder: impact of treatment with venlafaxine on the physiological and psychological responses to clonidine challenge.

Serotonin and noradrenaline reuptake inhibitor (SNRI) antidepressants have evidence of efficacy in the treatment of generalized anxiety disorder (GAD); however, it is not clear whether there is an advantage over selective serotonin reuptake inhibitor (SSRI) medicines and there is limited evidence for noradrenergic dysfunction in GAD. We tested whether a dysfunctional alpha-2 adrenoceptor system is present in patients with GAD and the effects of SNRI treatment on this system. The method used was an infusion of clonidine (a selective alpha-2 adrenergic receptor agonist) on psychological and physiological outcomes in three subject groups: 10 untreated GAD patients, five SNRI-treated GAD patients and seven normal controls. The clonidine challenge elicited sedation, a rise in growth hormone, decrease in blood pressure, decline in saccadic eye movement (SEM) variables, and improvement in verbal fluency as anticipated in the 22 subjects examined. Lower cortisol levels were found in controls and higher blood pressure readings in GAD-treated subjects, as well as evidence that GAD-treated subjects had SEMs that were intermediate between control and GAD subjects' scores and have less clonidine-induced sedation. The implications of these findings with reference to the study hypothesis in this small study are discussed.

The use of behavioural change techniques in the treatment of paediatric obesity: qualitative evaluation of parental perspectives on treatment.

BACKGROUND: Treatment for childhood obesity is characterized by nonattendance and widespread failure to achieve weight maintenance. The use of behavioural change methods is suggested for engaging families in changing lifestyles. Qualitative methods may improve understanding of patient perceptions, thus improving treatment. The present study aimed to explore the thoughts and feelings of parents whose children had undertaken dietetic consultations either employing behavioural change techniques or delivered by dietitians with no formal training in these techniques. METHODS: The study used purposive sampling, interviewing 17 parents of children attending 6-month outpatient treatments for obesity (body mass index > 98 th percentile). Parent's perceptions of the dietetic treatment were explored by in-depth interviews and analysed using Framework methods. RESULTS: Parents who had taken part in the behavioural change techniques applauded the process, finding it child-friendly and talked of 'forming a partnership'. Conversely, standard care treatment was less well received. Developing a rapport with the dietitian was significant for the parents in their perception of a positive experience. CONCLUSIONS: The present study may help inform future treatments for childhood obesity by providing insights into the aspects of treatment and approaches applauded by parents. It highlights the possible value of use of behavioural change skills by dietitians to engage with families of obese children.

Pharmacogenetics of hypersensitivity to abacavir: from PGx hypothesis to confirmation to clinical utility.

The hypersensitivity (HSR) to abacavir (ABC) pharmacogenetics (PGx) program represents the progression from an exploratory discovery to a validated biomarker. Within the program, two retrospective PGx studies were conducted to identify HIV-1 patients at increased risk for ABC HSR, a treatment-limiting and potentially life-threatening adverse event. A strong statistical association between the major histocompatibility complex allele, HLA-B*5701, and clinically diagnosed ABC HSR was identified but varied between racial populations. Subsequently, ABC skin patch testing was introduced as a research tool to supplement clinical case ascertainment. In a randomized, prospective study evaluating the clinical utility of HLA-B*5701 screening, avoidance of ABC in HLA-B*5701-positive patients significantly reduced clinically diagnosed ABC HSR and eliminated patch test-positive ABC HSR. Finally, a retrospective PGx study supports the generalizability of the association across races. Prospective HLA-B*5701 screening should greatly reduce the incidence of ABC HSR by identifying patients at high risk for ABC HSR before they are treated.

Parents' journey through treatment for their child's obesity: a qualitative study.

BACKGROUND: Treatment for childhood obesity is characterised by patient non-attendance and drop-out, and widespread failure to achieve weight maintenance. Qualitative methods may improve our understanding of patient perceptions and so improve treatment for childhood obesity. AIM: To provide insight into the perceptions of parents of obese children as they "journey" from pre-treatment to end of treatment. METHODS: We used purposive sampling and studied 17 parents of children (mean (SD) age 8.4 (2.1) years) attending 6-month outpatient treatments for obesity (BMI>98th percentile). Parent's perceptions were explored by in-depth interviews, analysed using Framework methods. RESULTS: Parents were characterised as being unaware of their child's weight, in denial or actively seeking treatment. Parents were consistently motivated to enter treatment due to perceived benefits to their child's self-esteem or quality of life, and weight outcomes appeared typically less important. During treatment parents felt there was a lack of support for lifestyle changes outside the clinic, and noted that members of the extended family often undermined or failed to support lifestyle changes. Parents generally felt that treatment should have continued beyond 6 months and that it had provided benefits to their child's well-being, self-esteem and quality of life, and this is what motivated many to remain engaged with treatment. DISCUSSION: This study may help inform future treatments for childhood obesity by providing insights into the aspects of treatment of greatest importance to parents. Future treatments may need to consider providing greater support for lifestyle changes within the extended family, and may need to focus more on psycho-social outcomes.

Use of pairwise marker combination and recursive partitioning in a pharmacogenetic genome-wide scan.

The objective of pharmacogenetic research is to identify a genetic marker, or a set of genetic markers, that can predict how a given person will respond to a given medicine. To search for such marker combinations that are predictive of adverse drug events, we have developed and applied two complementary methods to a pharmacogenetic study of the hypersensitivity reaction (HSR) associated with treatment with abacavir, a medicine that is used to treat HIV-infected patients. Our results show that both of these methods can be used to uncover potentially useful predictive marker combinations. The pairwise marker combination method yielded a collection of marker pairs that featured a spectrum of sensitivities and specificities. Recursive partitioning results led to the genetic delineation of multiple risk categories, including those with extremely high and extremely low risk of HSR. These methods can be readily applied in pharmacogenetic candidate gene studies as well as in genome-wide scans.

Quality of life in a clinical sample of obese children.

OBJECTIVES: To measure health-related quality of life (HRQoL) in a clinical sample of obese children by child self-report and parent-proxy report; to compare quality of life assessments provided by obese children and their parents; to assess differences in quality of life between the obese clinical sample and healthy control children. DESIGN: Pairwise comparison of obese children matched for age, gender and socio-economic status with non-obese controls. SUBJECTS: One hundred and twenty-six obese children (body mass index (BMI) >/=98th centile) and 71 lean control children (BMI <85th centile). Controls were matched with 71 children from the obese clinical group (mean age 8.6, standard deviation (s.d.) 1.9 years; 33 M/38 F). MEASUREMENT: The Paediatric Quality of Life Inventory (UK) version 4 was self-administered to parents and to children aged 8-12 years and interview was administered to children aged 5-7 years. This questionnaire assessed physical, social, emotional and school functioning from which total, physical and psychosocial health summary scores were derived. RESULTS: In the obese clinical group (n=126), parent proxy-reported quality of life was low for all domains. In the obese clinical group, parent-reported scores were significantly lower than child self-reported scores in all domains except physical health and school functioning. Parent-proxy reports were significantly higher for healthy controls than obese children in all domains (median total score 85.2 vs 64.7; 95% confidence interval (CI) 15.6, 24.1). For child self-reports, only physical health was significantly higher for healthy controls than obese children (median score 81.3 vs 75.0; 95% CI 3.1, 12.5). CONCLUSIONS: HRQoL is impaired in clinical samples of obese children compared to lean children, but the degree of impairment is likely to be greatest when assessed using the parent perspective rather than the child perspective.

Habitual physical activity and sedentary behaviour in a clinical sample of obese children.

OBJECTIVE: To objectively measure habitual physical activity and sedentary behaviour in a clinical sample of obese children and to compare with age- and sex-matched non-obese controls. DESIGN: Pairwise comparison of obese children matched for age and gender with non-obese controls. SUBJECTS: A total of 116 obese children (body mass index (BMI)> or =98th centile) and 53 non-obese control children (BMI<85th centile). Controls were matched with 53 of the obese children (mean age 8.6, s.d. 2.0 years; 25 M and 28 F). MEASUREMENT: Habitual physical activity and sedentary behaviour were measured over a 7-day period using CSA accelerometers. Total physical activity (mean accelerometry count per minute (c.p.m.)), percentage of monitored time in sedentary behaviour, light and moderate to vigorous intensity physical activity (MVPA) were compared. RESULTS: Obese children (n=116) spent on average 80.4% of their monitored time in sedentary behaviour and 2.5% of their monitored time in MVPA. Total activity (mean c.p.m.) was significantly higher in the non-obese group (n=53) than the obese group (n=53), 729 vs 648 c.p.m.; 95% confidence interval (CI) 7, 155. Time spent in sedentary behaviour averaged 80.9% (s.d. 6.6) in the obese group and 79.3% (s.d. 6.2) in the non-obese group, with no significant between-group difference (95% CI -3.9, 0.6). Light intensity activity was similar in the obese and non-obese groups (15.9 vs 17.3%; 95% CI -0.3, 3.0). Participation in MVPA was significantly higher in the non-obese vs obese group (3.9 vs 2.4%; 95% CI 0.6, 2.0). CONCLUSION: This study supports the hypothesis that a clinical sample of obese children is less physically active than non-obese children, although the difference in total activity and MVPA between the groups was small.