High temporal resolution delayed analysis of clinical microdialysate streams.

This paper presents the use of tubing to store clinical microdialysis samples for delayed analysis with high temporal resolution, offering an alternative to traditional discrete offline microdialysis sampling. Samples stored in this way were found to be stable for up to 72 days at -80 °C. Examples of how this methodology can be applied to glucose and lactate measurement in a wide range of in vivo monitoring experiments are presented. This paper presents a general model, which allows for an informed choice of tubing parameters for a given storage time and flow rate avoiding high back pressure, which would otherwise cause the microdialysis probe to leak, while maximising temporal resolution.

Online rapid sampling microdialysis (rsMD) using enzyme-based electroanalysis for dynamic detection of ischaemia during free flap reconstructive surgery.

We describe an enzyme-based electroanalysis system for real-time analysis of a clinical microdialysis sampling stream during surgery. Free flap tissue transfer is used widely in reconstructive surgery after resection of tumours or in other situations such as following major trauma. However, there is a risk of flap failure, due to thrombosis in the flap pedicle, leading to tissue ischaemia. Conventional clinical assessment is particularly difficult in such 'buried' flaps where access to the tissue is limited. Rapid sampling microdialysis (rsMD) is an enzyme-based electrochemical detection method, which is particularly suited to monitoring metabolism. This online flow injection system analyses a dialysate flow stream from an implanted microdialysis probe every 30 s for levels of glucose and lactate. Here, we report its first use in the monitoring of free flap reconstructive surgery, from flap detachment to re-vascularisation and overnight in the intensive care unit. The on-set of ischaemia by both arterial clamping and failure of venous drainage was seen as an increase in lactate and decrease in glucose levels. Glucose levels returned to normal within 10 min of successful arterial anastomosis, whilst lactate took longer to clear. The use of the lactate/glucose ratio provides a clear predictor of ischaemia on-set and subsequent recovery, as it is insensitive to changes in blood flow such as those caused by topical vasodilators, like papaverine. The use of storage tubing to preserve the time course of dialysate, when technical difficulties arise, until offline analysis can occur, is also shown. The potential use of rsMD in free flap surgery and tissue monitoring is highly promising.

A randomised controlled multicentre trial of treatments for adolescent anorexia nervosa including assessment of cost-effectiveness and patient acceptability - the TOuCAN trial.

OBJECTIVE: To evaluate the clinical effectiveness and cost-effectiveness of inpatient compared with outpatient treatment and general (routine) treatment in Child and Adolescent Mental Health Services (CAMHS) against specialist treatment for young people with anorexia nervosa. In addition, to determine young people's and their carers' satisfaction with these treatments. DESIGN: A population-based, pragmatic randomised controlled trial (RCT) was carried out on young people age 12 to 18 presenting to community CAMHS with anorexia nervosa. SETTING: Thirty-five English CAMHS in the north-west of England co-ordinated through specialist centres in Manchester and Liverpool. PARTICIPANTS: Two hundred and fifteen young people (199 female) were identified, of whom 167 (mean age 14 years 11 months) were randomised and 48 were followed up as a preference group. INTERVENTIONS: Randomised patients were allocated to either inpatient treatment in one of four units with considerable experience in the treatment of anorexia nervosa, a specialist outpatient programme delivered in one of two centres, or treatment as usual in general community CAMHS. The outpatient programmes spanned 6 months of treatment. The length of inpatient treatment was determined on a case-by-case basis on clinical need with outpatient follow-up to a minimum of 6 months. MAIN OUTCOME MEASURES: Follow-up assessments were carried out at 1, 2 and 5 years. The primary outcome measure was the Morgan-Russell Average Outcome Scale (MRAOS) and associated categorical outcomes. Secondary outcome measures included physical measures of weight, height, body mass index (BMI) and % weight for height. Research ratings included the Health of the National Outcome Scale for Children and Adolescents (HoNOSCA). Self report measures comprised the user version of HoNOSCA (HoNOSCA-SR), the Eating Disorder Inventory 2 (EDI-2), the Family Assessment Device (FAD) and the recent Mood and Feelings Questionnaire (MFQ). Information on resource use was collected in interview at 1, 2 and 5 years using the Child and Adolescent Service Use Schedule (CA-SUS). Satisfaction was measured quantitatively using a questionnaire designed for the study and qualitative (free) responses on it. The questionnaire data were supplemented by qualitative analysis of user and carer focus groups. RESULTS: Of the 167 patients randomised, 65% adhered to the allocated treatment. Adherence was lower for inpatient treatment (49%) than for general CAMHS (71%) or specialist outpatient treatment (77%) (p = 0.013). Every subject was traced at both 1 and 2 years, with the main outcome measure completed (through contact with the subject, family members or clinicians), by 94% at 1 year, 93% at 2 years, but only 47% at 5 years. A validated outcome category was assigned for 98% at 1 year, 96% at 2 years and 60% at 5 years. There was significant improvement in all groups at each time point, with the number achieving a good outcome being 19% at 1 year, 33% at 2 years and 64% (of those followed up) at 5 years. Analysis demonstrated no difference in treatment effectiveness of randomisation to inpatient compared with outpatient treatment, or, specialist over generalist treatment at any time point, when baseline characteristics were taken into account. Generalist CAMHS treatment was slightly more expensive over the first 2 years of the study, largely because greater numbers were subsequently admitted to hospital after the initial treatment phase. The specialist outpatient programme was the dominant treatment in terms of incremental cost-effectiveness. Specialist treatments had a higher probability of being more cost-effective than generalist treatments and outpatient treatment had a higher probability of being more cost-effective than inpatient care. Parental satisfaction with treatment was generally good, though better with specialist than generalist treatment. Young people's satisfaction was much more mixed, but again better with specialist treatment, including inpatient care. CONCLUSION: Poor adherence to randomisation (despite initial consent to it), limits the assessment of the treatment effect of inpatient care. However, this study provides little support for lengthy inpatient psychiatric treatment on clinical or health economic grounds. These findings are broadly consistent with existing guidelines on the treatment of anorexia nervosa, which suggest that outpatient treatments should be offered to the majority, with inpatient treatment offered in rare cases, though our findings lend little support to a stepped-care approach in which inpatient care is offered to outpatient non-responders. Outpatient care, supported by brief (medical) inpatient management for correction of acute complications may be a preferable approach. The health economic analysis and user views both support NICE guidelines, which suggest that anorexia nervosa should be managed in specialist services that have experience and expertise in its management. Comprehensive general CAMHS might, however, be well placed to manage milder cases. Further research should focus on the specific components of outpatient psychological therapies. Although family-based treatments are well established, trials have not established their effectiveness compared with good-quality individual psychological therapies and the combination of individual and family approaches is untested. Further research is needed to establish which patients (if any) might respond to inpatient psychiatric treatment when unresponsive to outpatient care, the positive and negative components of it and the optimum length of stay. TRIAL REGISTRATION: NRR number (National Research Register) N0484056615; Current Controlled Trials ISRCTN39345394.

Cognitive-behavioural therapy for adolescents with bulimic symptomatology: the acceptability and effectiveness of internet-based delivery.

BACKGROUND: The evidence base for the treatment of adolescents with bulimia nervosa (BN) is limited. AIMS: To assess the feasibility, acceptability, and clinical outcomes of a web-based cognitive-behavioural (CBT) intervention for adolescents with bulimic symptomatology. METHOD: 101 participants were recruited from eating disorders clinics or from beat, a UK-wide eating disorders charity. The programme consisted of online CBT sessions ('Overcoming Bulimia Online'), peer support via message boards, and email support from a clinician. Participants' bulimic symptomatology and service utilisation were assessed by interview at baseline and at three and six months. Participants' views of the treatment package were also determined. RESULTS: There were significant improvements in eating disorder symptoms and service contacts from baseline to three months, which were maintained at six months. Participants' views of the intervention were positive. CONCLUSIONS: The intervention has the potential for use as a first step in the treatment of adolescents with bulimic symptomatology.

Validity of the Eating Disorders Examination-Questionnaire when used with adolescents with bulimia nervosa and atypical bulimia nervosa.

OBJECTIVE: To validate the online questionnaire form of the Eating Disorders Examination (EDE-Q) against the interview version (EDE) in a clinic and community sample of adolescents with bulimia nervosa (BN) or atypical BN (eating disorder not otherwise specified with bulimic features - EDNOS-BN). METHOD: Adolescents with BN (N=58) or EDNOS-BN (N=37) completed the EDE over the telephone and the EDE-Q online. RESULTS: There were moderate to high correlations between the attitudinal scales. Eating was rated as more pathological on the EDE-Q than the EDE, except dietary restraint. As in research among adults, agreement between the two measures was low regarding binge eating episodes, but better for vomiting episodes. When compared with the EDE, the EDE-Q attitudinal scales were more valid for BN than for EDNOS-BN patients, and more valid for the clinic sample. CONCLUSION: The online version of the EDE-Q has partial validity for use with adolescents. The EDE-Q might be reporting a more accurate description of current status, as it avoids possible filtering and approval aspects.

Management of eating disorders in children and adolescents.

The eating disorders, anorexia nervosa, bulimia nervosa and their variants, typically develop in adolescence or early adulthood, mainly in females. Despite a long history, the evidence base for effective treatments is weak and existing clinical guidelines are based on consensus views rather than strong research. Effective coordinated management of physical and psychological aspects of the disorders is crucial, but outcomes remain very variable, with adverse outcomes commonly extending into adulthood. Anorexia nervosa carries a high morbidity and occasional mortality.

Development of weight and shape concerns in the aetiology of eating disorders.

BACKGROUND: Although weight and shape concerns are considered to be integral to the psychopathology of anorexia and bulimia nervosa, uncertainties remain about developmental aspects of the aetiology of these concerns and their relationship to eating disorders. AIMS: To review the recent literature on weight and shape concern, with particular emphasis on aetiology, to identify a possible developmental pathway from weight concern through abnormal eating behaviour to disorder. METHOD: Literature review of Medline and Psychlit databases using the keywords 'eating disorder', 'weight concern', 'shape concern' and 'aetiology'. Inclusion criteria were based on the strength of quantitative research findings, originality of ideas and recent publication. RESULTS: Weight and shape concerns follow a developmental pathway arising before the typical age for the development of eating disorders. The origins are multifactorial, with biological, family and sociocultural features predominating. CONCLUSIONS: Although weight and shape concern seems commonly to underlie the development of eating disorders, an alternative pathway appears to exist through impulsivity and fear of loss of control. Prevention strategies may usefully focus on the attitudes and concerns that lead to dieting behaviour.

Enuresis and encopresis in a south Indian population of children.

INTRODUCTION: Though bladder and bowel control are important developmental milestones in all cultures, the prevalence of enuresis and encopresis has rarely been studied in developing countries despite there being factors in these countries that could affect it. This study reports the prevalence and associations of enuresis and encopresis in children in Kerala, India. METHOD: The parents of 1403 randomly selected 8-12-year-old children were interviewed. The prevalence of enuresis and encopresis was ascertained using Rutter's A2 scale. Subsamples of children underwent psychiatric, physical and psychometric evaluations. RESULTS: Of the children, 18.6% had had an episode of enuresis in the past year and 4.3% in the past week. Four per cent had had an episode of encopresis in the past year. Enuresis was associated with parents' education, physical and psychiatric symptoms in the child, poor academic achievement and lax parental attitudes to toilet training. Encopresis was associated with male sex, physical and psychiatric symptoms, poor academic achievement, early separation and not having a toilet. DISCUSSION: The prevalence of enuresis compares with western countries, but encopresis is commoner. The associations of enuresis suggested a multifactorial model in which parental competence was prominent. This study de-emphasized the importance of neurodevelopmental factors in enuresis and encopresis in this age group.

Life events in a South Indian population and their association with psychiatric disorder in children.

Western research suggests that life events contribute to childhood psychiatric disorder but no studies have examined this in developing countries. During a population-based study of 1,403 8-12 year old children in Kerala, South India, a life events schedule was administered to parents of children with ICD10 psychiatric disorders (n = 72) and controls. Life events were associated with lower social class, greater poverty, less educated parents, worse physical health and psychiatric disorder. Multivariate analysis confirmed the association of life events with psychiatric disorder, independent of indices of social adversity.

Parental high concern and adolescent-onset anorexia nervosa. A case-control study to investigate direction of causality.

BACKGROUND: Robust evidence that anorexia nervosa is preceded rather than accompanied by high-concern (overprotective) parenting is limited. AIMS: To look for evidence of parental high concern occurring before any onset of disorder. METHOD: Forty consecutive referrals of adolescent girls with DSM-III-R anorexia nervosa were compared with matched controls using obstetric records and maternal interviews. RESULTS: Index mothers reported higher rates of: near-exclusive child care (P = 0.02), infant sleep difficulties (P = 0.018), severe distress at first regular separation (P = 0.048), high maternal trait anxiety levels (P = 0.008) and later age for first sleeping away from home (P = 0.009). More index families had experienced a severe obstetric loss prior to their daughter's birth (P = 0.066). CONCLUSIONS: This study lends evidence to the clinical contention that high-concern parenting in infancy is associated with the later development of anorexia nervosa. This may derive, in part, from aspects of unresolved grief.

Impact of hospitalisation on the outcome of adolescent anorexia nervosa.

BACKGROUND: Owing to the lack of controlled trials of treatment setting in adolescent anorexia nervosa, the benefits and costs of in-patient treatment are not established. AIMS: To clarify the relationship between a range of presenting features, treatment received and medium- to long-term outcome in adolescent anorexia nervosa. METHOD: A range of presenting variables were rated for 75 cases of DSM-III-R anorexia nervosa at presentation to an adolescent service, including the Morgan-Russell Global Assessment Score. Cases were followed up at 2-7 years and outcome rated according to reliable methods. Setting of treatment received was also recorded. RESULTS: Two out of 75 cases had died by the time of follow-up. Adequate data for 72 enabled an outcome category to be assigned. The 21 who had received inpatient treatment had a significantly worse outcome than the 51 never admitted to hospital. Multivariate analysis suggests admission to be the major predictor of poor outcome. CONCLUSIONS: The benefits and costs of admission to hospital require further investigation, ideally in a randomised-controlled trial. The negative consequences of in-patient treatment are neglected in research.

Anorexia nervosa, psychopathology, and outcome.

OBJECTIVE: To examine for specificity of Eating Disorders Inventory (EDI) ratings and differences in self-reported cognitions and clinical outcome between adolescent cases of anorexia nervosa (AN) with and without comorbid depression. METHOD: Thirty-five subjects with AN and matched psychiatric and community controls received the EDI and a structured diagnostic interview. AN subjects were followed up at 1 and 2 years using the EDI and a semistructured interview to assess outcome. RESULTS: Subjects with AN and those with other psychiatric disorders scored similarly on the EDI. Differences between AN cases and community controls were marked for comorbid cases but rare for noncomorbid cases. Comorbid AN cases had an equally good outcome compared to those with AN alone. DISCUSSION: Abnormal cognitions reported in the EDI are much greater in those cases with comorbid depression, but neither the presence of depression nor high EDI scores appears to adversely affect prognosis.

The prevalence and associations of psychiatric disorder in children in Kerala, South India.

This study aimed to identify the prevalence and associations of childhood psychiatric disorder in Calicut District, South India. Among 1403 children aged 8 to 12 years selected by random cluster sampling, a projected prevalence of 9.4% (95% CI 7.9-10.8%) was found. Associations of disorder with male sex, the Muslim religion, lower social class, less parental education, school failure, and impaired reading and vocabulary were found, but not with malnutrition or perinatal problems. The similarity to associations of disorder in Western studies was noted. The discussion focuses on the validity of comparisons of prevalence across cultures.

Difficulties in family functioning and adolescent anorexia nervosa.

BACKGROUND: Difficulties in family functioning are often evident when an adolescent has anorexia nervosa, and the possible causative or contributory role of such difficulties in the illness is unclear. AIMS: To elucidate the relationship between severity of anorexia nervosa and difficulties in family functioning and whether clinical improvement results in diminution of self-rated family difficulties. METHOD: Thirty-five adolescents with anorexia nervosa and their mothers completed the Family Assessment Device (FAD) while clinicians administered the McMaster's Structured Interview of Family Functioning (McSIFF). Severity of anorexia nervosa was rated at baseline and at one year follow-up using the Morgan-Russell Schedule. RESULTS: Clinicians and patients were more critical of the families' functioning than parents. There was an inverse association between the extent of family difficulties and severity of anorexia nervosa. Over time subjects improved clinically but this was not matched by improvement in family functioning. CONCLUSIONS: Difficulties in family functioning do not appear to be directly associated with severity of anorexia nervosa nor do these difficulties reduce with clinical improvement, in the short term.

Brief scale for measuring the outcomes of emotional and behavioural disorders in children. Health of the Nation Outcome Scales for children and Adolescents (HoNOSCA).

BACKGROUND: Following the development of a child and adolescent version of the Health of the Nation Outcome Scales (HoNOSCA), field trials were conducted to assess their feasibility and acceptability in routine outcome measurement. AIMS: To evaluate the reliability, validity and acceptability of HoNOSCA in routine outcome measurement. METHOD: Following training, 36 field sites provided ratings on 1276 cases at one time point and outcome data on 906. Acceptability was assessed by way of written feedback and at a debriefing meeting. RESULTS: HoNOSCA demonstrated satisfactory reliability and validity characteristics. It was sensitive to change and its ability to measure change accorded with the clinicians' independent rating. HoNOSCA was reasonably acceptable to clinicians' from a range of disciplines and services. CONCLUSIONS: Provided that training needs can be met, HoNOSCA represents a satisfactory brief outcome measure which could be used routinely in child and adolescent mental health services.

The stigma of eating disorders.

Those who suffer from eating disorders often carry the added burden of stigmatizing attitudes from the lay public and the medical profession. These attitudes not only restrict the opportunities for effective treatment but also confer additional handicaps. To some extent, stigmatizing beliefs are based on partial truths about these disorders, namely their dangerousness, their sometimes poor response to treatment, the sufferers' part in their maintenance, and difficulties in communication. This review explores the truth of these beliefs and suggests ways in which a more positive approach to the management of eating disorders might help to reduce the stigma. This includes empathy with the patient's predicament and an approach to treatment in which the patient's wishes are paramount.

Family functioning and life events in the outcome of adolescent anorexia nervosa.

BACKGROUND: This study investigates the outcome of anorexia nervosa in adolescents in relation to precipitating life events and changes in family functioning over time. METHOD: Thirty-five adolescents with anorexia nervosa and their mothers were administered measures of life events and family functioning at initial assessment and 1 and 2 year follow-up, when outcome was also assessed. RESULTS: Fifty-five per cent of patients had a good outcome. Patients from initially well-functioning families or those with precipitating life events improved more in the first year, than those with dysfunctional families or without events. Subjects perceived a deterioration in family functioning at 1 year follow-up but an improvement at 2 years. Mothers reported no changes. CONCLUSIONS: Approximately half of a series of early onset cases of anorexia nervosa can be expected to recover by 2 years. Healthy family functioning and presence of a precipitating life event predict good short-term outcome. The relationships between subjects' perceptions of family functioning and their recovery from anorexia nervosa is discussed.

Pilot study of continuation cognitive-behavioral therapy for major depression in adolescent psychiatric patients.

OBJECTIVE: To determine whether continuation of cognitive-behavioral therapy (CBT-C) could prevent relapse in adolescent psychiatric patients who had remitted from major depressive disorder (MDD). METHOD: Seventeen patients who continued to have CBT-C for 6 months after remission from MDD were compared with a historical control group of 12 cases who had no further treatment after remission. RESULTS: Only 1 of the 17 cases who continued with CBT-C dropped out. The cumulative relapse risk during CBT-C was significantly lower (0.2) than it had been in the historical control group (0.5). CONCLUSIONS: CBT-C warrants further investigation in a randomized, controlled trial.

Life event precipitants of adolescent anorexia nervosa.

As part of a prospective outcome study, independent life events occurring in the year before onset in 35 consecutive cases of anorexia nervosa were recorded by a semi-structured interview with the subject and a parent. Negative impact and context were rated blind, using the case vignette method. Subjects with anorexia reported intermediate rates of negative life events between community and psychiatric controls. Chronic adversities were common. Negative life events were associated with depressive disorder in controls, but not in those with anorexia. Significant under-reporting of events may occur in this population.