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A fully automated and GMP compatible synthesis has been developed to reliably label the M1 receptor agonist GSK1034702 with carbon-11. Stille reaction of the trimethylstannyl precursor with [11C]methyl iodide afforded [11C]GSK1034702 in an estimated 10±3% decay corrected yield. This method utilises the commercially available modular laboratory equipment and provides high purity [11C]GSK1034702 in a formulation suitable for human use.

Opioid neurotransmission has a key role in mediating reward-related behaviours. Opioid receptor (OR) antagonists, such as naltrexone (NTX), can attenuate the behaviour-reinforcing effects of primary (food) and secondary rewards. GSK1521498 is a novel OR ligand, which behaves as an inverse agonist at the μ-OR sub-type. In a sample of healthy volunteers, we used [(11)C]-carfentanil positron emission tomography to measure the OR occupancy and functional magnetic resonance imaging (fMRI) to measure activation of brain reward centres by palatable food stimuli before and after single oral doses of GSK1521498 (range, 0.4-100 mg) or NTX (range, 2-50 mg). GSK1521498 had high affinity for human brain ORs (GSK1521498 effective concentration 50 = 7.10 ng ml(-1)) and there was a direct relationship between receptor occupancy (RO) and plasma concentrations of GSK1521498. However, for both NTX and its principal active metabolite in humans, 6-β-NTX, this relationship was indirect. GSK1521498, but not NTX, significantly attenuated the fMRI activation of the amygdala by a palatable food stimulus. We thus have shown how the pharmacological properties of OR antagonists can be characterised directly in humans by a novel integration of molecular and functional neuroimaging techniques. GSK1521498 was differentiated from NTX in terms of its pharmacokinetics, target affinity, plasma concentration-RO relationships and pharmacodynamic effects on food reward processing in the brain. Pharmacological differentiation of these molecules suggests that they may have different therapeutic profiles for treatment of overeating and other disorders of compulsive consumption.

Objectives: The aim of the study was to identify prognostic factors for the persistence of chronic abdominal pain (CAP) in children. Materials and Methods: For this systematic review, MEDLINE, EMBASE, and PsycINFO were searched up to June 2008 for prospective follow-up studies of pediatric CAP as defined by the criteria of Apley, von Baeyer, or the Rome Committee. The outcome measure of interest was persistence of CAP. Persistent CAP was considered only when the abdominal pain of children with CAP persisted during follow-up at the same level of frequency and severity. For each study the risk for bias was assessed. The evidence for prognostic factors was summarized according to a best-evidence synthesis. Results: Eight studies, which examined 17 prognostic factors, were included. Moderate evidence was found that having a parent with gastrointestinal symptoms predicts the persistence of CAP. Strong evidence was found for no association between female sex and the duration of CAP, and moderate evidence that the severity of abdominal pain does not predict persistence of CAP. There is conflicting evidence as to whether psychological factors prevent, or have no relation to, persistence of CAP. Conclusions: Because there are few prognostic follow-up studies on pediatric CAP, the evidence for prognostic factors is limited. Physicians should ask about parental gastrointestinal problems because this is a risk factor for persistence of CAP in children. The hypothesis that psychological factors of the child predict persistence of CAP is not supported by evidence from follow-up studies.

Purpose: The efficacy of population-based vision screening is hampered by unsuccessful referral after a positive screening test. We studied the nature and causes of unsuccessful referral in a 7-year birth cohort study of vision screening in Rotterdam, the Netherlands. Methods: All parents of children who had been unsuccessfully referred were asked whether they recalled the referral. Reasons for noncompliance, if any, were identified using semi-structured interviews. Screening records were checked for written evidence of the referral. The parents' fluency in Dutch and their socioeconomic status were also assessed. Results: Of the 561 screen-positive children, 129 (23%) had not been referred successfully. For the current study, 97 parents were successfully contacted. Of these, 14 parents had been willingly noncompliant and 83 said they were unaware of the referral, with 47% having poor to moderate fluency in Dutch. In 53 cases, the screening charts contained no written evidence of any referral. Amblyopia was identified in 3 of the unsuccessful referrals. Conclusions: In this population-based screening program, 1 of 4 positively screened children was not successfully referred. Apart from parental noncompliance, the unsuccessful referrals can be explained by miscommunication, deficient documentation, and physician noncompliance with screening guidelines. An effective monitoring feedback system may improve the efficacy of child vision screening. © 2011 by the American Association for Pediatric Ophthalmology and Strabismus.

Objective. To determine baseline predictors of treatment success in terms of Body Mass Index-Standard Deviation Scores (BMI-SDS) in a multidisciplinary family-based behavioural lifestyle intervention for overweight and obese children. Methods. Overweight and obese children (N = 248; age 814 years) and their caregivers participated in a prospective study and attended a lifestyle intervention. Baseline data assessment included anthropometrics, demographics, breakfast behaviour, competence and behavioural problems (Child Behaviour Checklist [CBCL]), family functioning (Family Adaptability and Cohesion Evaluation Scales [FACES] III), and personality (Dutch Personality Questionnaire-Youth [NPV-J]). BMI-SDS was measured at start and after 3, 9, and 12 months of treatment. Mixed modelling was used for analysis. Results. Greater BMI-SDS reductions over the course of one year were found in children with Caucasian parents, with lower baseline BMI-SDS, and higher CBCL-social competence scores. Furthermore, children with non-overweight parents, younger children, and children with lower CBCL-somatic scores were more successful in BMI-SDS reduction. No effects on treatment success were found for the number or position of siblings, having divorced parents or a working mother, educational level of the parents, breakfast behaviour, family functioning, and personality. Conclusions. These results suggest that screening for baseline characteristics in childhood obesity treatment could identify who will benefit most from a paediatric lifestyle intervention. Tailored programs should be developed and the treatment team should focus on children who are less successful in achieving weight reductions. Future research should study by which mechanisms somatic complaints and social competence influence treatment success. © 2011 Informa Healthcare.

Background Compliance with occlusion therapy for amblyopia in children is low when their parents have a low level of education, speak Dutch poorly, or originate from another country. We determined how sociocultural and psychological determinants affect compliance. Methods Included were amblyopic children between the ages of 3 and 6, living in low socio-economic status (SES) areas. Compliance with occlusion therapy was measured electronically. Their parents completed an oral questionnaire, based on the “Social Position & Use of Social Services by Migrants and Natives” questionnaire that included demographics and questions on issues like education, employment, religion and social contacts. Parental fluency in Dutch was rated on a five-point scale. Regression analysis was used to describe the relationship between the level of compliance and sociocultural and psychological determinants. Results Data from 45 children and their parents were analyzed. Mean electronically measured compliance was 56 ± 44 percent. Children whose parents had close contact with their neighbors or who were highly dependent on their family demonstrated low levels of compliance. Children of parents who were members of a club and who had positive conceptualizations of Dutch society showed high levels of compliance. Poor compliance was also associated with low income, depression, and when patching interfered with the child’s outdoor activity. Religion was not associated with compliance. Conclusions Poor compliance with occlusion therapy seems correlated with indicators of social cohesion. High social cohesion at micro level, i.e., family, neighbors and friends, and low social cohesion on macro level, i.e., Dutch society, are associated with noncompliance. However, such parents tend to speak Dutch poorly, so it is difficult to determine its actual cause. Electronic supplementary material The online version of this article (doi:10.1007/s00417-011-1637-5) contains supplementary material, which is available to authorized users.

Background. Behavioral dyscontrol and violations of treatment contracts are serious clinical problems during psychotherapy, especially in treating patients with personality disorders. However, little is known about predictors of these treatment-interfering phenomena. Objective. To identify psychodynamic personality characteristics that can interfere with the psychotherapy process as indicated by treatment-disrupting behaviors. Methods. Sociodemographic characteristics, descriptive psychiatric diagnoses, and psycho-dynamic characteristics were assessed in 89 inpatients with personality disorders in psychotherapeutic treatment. Psychodynamic charac teristics were assessed with the Develop mental Profile (DP). DP variables were used to predict impulsive acts, anger outbursts, para-suicidal behaviors, and contract violations. Incremental value was established. Results. In this sample, 4 out of 5 patients engaged in treatment-interfering behaviors during the first 3 months of therapy. In general, treatment-disrupting behaviors were not predicted by baseline DSM-IV Axis I or II disorders. In contrast, impulsive behaviors, anger outbursts, and contract violations were significantly predicted by psychodynamic variables, especially the DP levels Fragmentation and Egocentricity. DP variables accounted for an incremental predictive value of 23% for treatment-disrupting behaviors, over and above demographics and descriptive diagnoses. Para-suicidal gestures were not predicted by either DSM-IV diagnoses or psychodynamic variables. Conclusion. Psychodynamic personality variables significantly predicted impulsive behaviors, outbursts of anger, and treatment contract violations during psychotherapeutic treatment. The amount of explained variance and incremental value was substantial. These findings support the relevance of psychodynamic assessment in clinical practice. Copyright © 2011 Lippincott Williams & Wilkins Inc.

The objective of this study was to investigate the association between psychological factors and complex regional pain syndrome type 1 (CRPS1). A prospective multicenter cohort study was performed involving the emergency room of three hospitals, and patients age 18 years or older, with a single fracture, were included in the study. At baseline (T0), participants completed a questionnaire covering demographic, psychological (Symptom Checklist-90), and medical variables. At plaster removal (T1) and at T2, the participants completed a questionnaire addressing symptoms of CRPS1. Psychological factors that were analysed were agoraphobia, depression, somatization, insufficiency, (interpersonal) sensitivity, insomnia, and life events. In total, 596 consecutive patients were included in the study, and 7.0% were diagnosed with CRPS1. None of the psychological factors predicted the development of CRPS1. The scores on the Symptom Checklist-90 subscales fell into the range of the general population and were, in most cases, average or below average when compared with those of pain patients or psychiatric patients. No empirical evidence supports a diagnosis of CRPS1 patients as psychologically different, and the current results indicate that there is no association between psychological factors and CRPS1. © 2011 Elsevier Inc. All rights reserved.

OBJECTIVE: To evaluate baseline predictors of drop out at various stages in a lifestyle intervention for overweight and obese children. PATIENTS AND METHODS: Children and their families (N = 248) (aged 8–14 years) attended a lifestyle intervention. At baseline, we assessed anthropometric and demographic data, measured competence and behavioral problems, and family functioning. Dropout rates were analyzed at various stages in treatment with logistic regression analyses. RESULTS: Children who had mothers of non-white descent, who had higher BMI SDS, who participated in fewer activities, who did not have breakfast regularly, and who did not live in families with a static adaptability structure were more likely to drop out between 0 and 12 months. Different characteristics predicted dropout at various stages of treatment: (1) having an ethnic minority status and being older predicted dropping out between 0 and 3 months; (2) having a nonwhite mother, participating in fewer activities, having higher delinquency scores, and not presenting the family as extremely positive predicted dropping out between 3 and 9 months; and (3) having a higher BMI SDS, having fewer social problems, and not living in families with a static adaptability structure predicted dropping out between 9 and 12 months of treatment. CONCLUSIONS: The results indicate diffrerent characteristics predict dropping out from a pediatric lifestyle program at various stages in treatment. These findings highlight the need for tailored interventions that target different characteristics at various stages of treatment to reduce drop out rates.

Background: Patients with severe congenital facial disfigurement have a long track record of operations and hospital visits by the time they are 18 years old. The fact that their facial deformity is congenital may have an impact on how satisfied these patients are with their appearance. This study evaluated the level of satisfaction with facial appearance of congenital and of acquired facially disfigured adults, and explored demographic, physical and psychological determinants of this satisfaction. Differences compared with non-disfigured adults were examined. Methods: Fifty-nine adults with a rare facial cleft, 59 adults with a facial deformity traumatically acquired in adulthood, and a reference group of 201 non-disfigured adults completed standardised demographic, physical and psychological questionnaires. Results: The congenital and acquired groups did not differ significantly in the level of satisfaction with facial appearance, but both were significantly less satisfied than the reference group. In facially disfigured adults, level of education, number of affected facial parts and facial function were determinants of the level of satisfaction. High fear of negative appearance evaluation by others (FNAE) and low self-esteem (SE) were strong psychological determinants. Although FNAE was higher in both patient groups, SE was similar in all three groups. Conclusion: Satisfaction with facial appearance of individuals with a congenital or acquired facial deformity is similar and will seldom reach the level of satisfaction of non-disfigured persons. A combination of surgical correction (with attention for facial profile and restoring facial functions) and psychological help (to increase SE and lower FNAE) may improve patient satisfaction. (C) 2009 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

The type-1 glycine transporter (GlyT1) is an important target for the development of new medications for schizophrenia. A specific and selective positron emission tomography (PET) GlyT1 ligand would facilitate drug development studies to determine whether a drug reaches this target and help establish suitable doses for clinical trials. This article describes the evaluation of three candidate GlyT1 PET radioligands (GSK931145, GSK565710, and GSK991022) selected from a library of compounds based on favorable physicochemical and pharmacological properties. Each candidate was successfully labeled using [11C]methyl iodide or [11C]methyl triflate and administered to a pig pre- and postadministration with a pharmacological dose of a GlyT1 inhibitor to determine their suitability as PET ligands in the porcine brain in vivo. All three candidate ligands were analyzed quantitatively with compartment analyses employing a plasma input function. [11C]GSK931145 showed good brain penetration and a heterogeneous distribution in agreement with reported GlyT1 localization. Following pretreatment with GSK565710, uptake of [11C]GSK931145 was reduced to homogeneous levels. Although [11C]GSK565710 also showed good brain penetration and a heterogeneous distribution, the apparent level of specific binding was reduced compared to [11C]GSK931145. In contrast, [11C]GSK991022 showed a much lower brain penetration and resultant signal following pretreatment with GSK565710. Based on these findings [11C]GSK931145 was identified as the most promising ligand for imaging GlyT1 in the porcine brain, possessing good brain penetration, specific signal, and reversible kinetics. [11C]GSK931145 is now being progressed into higher species. Synapse 64:542–549, 2010. © 2010 Wiley-Liss, Inc.

To assess the efficacy and tolerability of prophylactic drugs for chronic tension-type headache (TTH) in adults.We searched several databases from inception to August 2009. We selected randomized trials that reported the effects of prophylactic drugs in patients with TTH, with a pain measure (intensity, frequency, duration, improvement or index) as outcome measure. Two authors independently assessed risk of bias and extracted data from the original reports. A data synthesis was carried out according to the type of medication.We included 44 trials (3399 patients), of which 15 (34.1%) were considered to be of low risk of bias. Main types of medications studied were antidepressants, muscle relaxants, benzodiazepines and vasodilator agents. Overall, antidepressants were no more effective than placebo, and there were no significant differences between different types of antidepressants. There was conflicting evidence about the effectiveness of benzodiazepines and vasodilator agents compared with placebo. Furthermore, there was limited evidence that propranolol had negative effects on depression in TTH patients, when compared with placebo or biofeedback. There was no evidence concerning the effectiveness of muscle relaxants alone or 5-HT receptor agonist compared with placebo.Overall, antidepressants were no more effective on headache intensity or frequency and analgesic use than placebo. Propranolol seemed to have negative effects on depression in TTH patients when compared with placebo or biofeedback. No evidence was found for the use of muscle relaxants alone or 5-HT receptor agonist.

More control over migraine 6 months after the behavioural self-management training by lay trainers with migraine

Background: Riboflavin seems to have a promising effect on migraine in adults. The present study examines whether riboflavin has a prophylactic effect on migraine in children. Objective: To investigate whether riboflavin in a dosage of 50 mg/day has a prophylactic effect on migraine attacks in young children. Subjects and methods: This randomised, placebo-controlled, double-blind, cross-over trial included 42 children (aged 6–13 years) with migraine of whom 14 children were also suffering from tension-type headache. Following a 4-week baseline period, all children received placebo for 16 weeks then riboflavin for 16 weeks (or vice versa) with a washout period of 4 weeks in between. The primary outcome measure was reduction in mean frequency of migraine attacks and tension-type headache in the last 4 weeks at the end of the riboflavin and placebo phase, compared with the preceding baseline or wash-out period. Secondary outcome measures were mean severity and mean duration of migraine and tension-type headaches in the last 4 weeks at the end of the riboflavin and placebo phase, compared with the preceding baseline or wash-out period. Results: No significant difference in the reduction of mean frequency of migraine attacks in the last month of treatment was found between placebo and riboflavin ( P = 0.44). However, a significant difference in reduction of mean frequency of headaches with a tension-type phenotype was found in favour of the riboflavin treatment ( P = 0.04). Conclusions: In this group of children with migraine, there is no evidence that 50 mg riboflavin has a prophylactic effect on migraine attacks. We found some evidence that 50 mg riboflavin may have a prophylactic effect on interval headaches that may correspond to mild migraine attacks or tension-type headache attacks in children with migraine.

Background The characteristics of polycystic ovary syndrome (PCOS) such as hyperandrogenism and anovulation can be highly stressful and might negatively affect psychological well-being and sexuality. The objective of this study was to evaluate the association between PCOS characteristics and psychological well-being as well as sexarche. Methods Patients (n = 1148) underwent standardized clinical evaluation. Psychological well-being was investigated in 480 patients with the Rosenberg self-esteem scale (RSES), the body cathexis scale (BCS) and the fear of negative appearance evaluation scale (FNAES). Sexarche was also assessed. Result SAmenorrhoea was associated with lower self-esteem (P = 0.03), greater fear of negative appearance evaluation (P = 0.01) and earlier sexarche (P= 0.004). Hyperandrogenism and acne were associated with poorer body satisfaction (P = 0.03, 0.02, respectively). Hirsutism and BMI were negatively associated with all psychological variables (RSES, P = 0.01; BCS, P = 0.05; FNAES, P = 0.02 and RSES, P = 0.03; BCS, P = 0.001; FNAES, P = 0.03, respectively). Conclusions Our Results suggest that menstrual irregularities might be related to sexarche. Moreover, this study stresses that the treatment of women with PCOS should notably focus on physical but also on psychological and sexual characteristics. © The Author 2010.

To investigate the effect of child temperament, maternal psychologic symptoms, maternal chronic pain, and parenting stress on children's somatic complaints.The study was embedded in the Generation R Study, a population-based cohort study. Child somatic complaints were assessed via mother-report in 5,171 children of 18 months of age. Questionnaires assessed maternal somatic symptoms, symptoms of depression, anxiety during pregnancy and 2 months after delivery, maternal chronic pain during pregnancy, parenting stress 18 months after birth, and mother-reported child temperament 6 months after birth, as the determinants.Fearful temperament, temperamental falling reactivity, maternal somatic symptoms, anxiety symptoms, and parenting stress each independently and prospectively increased the likelihood of children's somatic complaints at 18 months of age.In toddlers, temperament, maternal stress, and maternal somatic symptoms seem particularly important for the development of somatic complaints, but long-term research is needed to establish causality and predictive value of these factors.

(Headache 2010;50:613-625) Objectives.— To evaluate the qualities of lay trainers with migraine and to quantify their self-management results. Background.— Little is known about the qualities of lay trainers with chronic diseases and the benefits for their own health. Methods.— Thirteen lay trainers (12 F, 1 M) completed a 3-step program that consisted of self-experience of a behavioral training (BT), providing BT to one fellow patient, and subsequently to a small group at home. Successful mastery of own migraine attacks was required for participation, and lay trainers received intensive guidance. Evaluation of the qualities of trainers took place post-BT by means of a specially constructed questionnaire. Their self-management was measured before self-experience of BT, post-BT, and at 6-month follow-up by a headache diary and questionnaires. Results.— The qualities of the 13 trainers were positively evaluated by 95 trainees, particularly their warmth, expertise, organization, explanation of BT, active control, and advice and guidance. Higher active control of lay trainers during the group sessions was significantly related to improvements on migraine frequency and internal locus of control in their trainees post-BT. Advice and guidance increased the likelihood of less attacks at follow-up and supportive encouragement promoted a higher internal locus of control. However, humor slightly increased the likelihood of more attacks post-BT, while fellowship and individualization negatively influenced internal locus of control. Lay trainers showed significantly more improvement in migraine frequency than their trainees at follow-up, as well as enhanced internal locus of control and quality of life. Conclusions.— Participation in a stepwise training program can produce capable trainers and may positively influence their own health. Lay trainers may be more motivated to enhance their self-management skills as they have to present the benefits to their trainees.

Context: There has been little systematic attempt to validate current pharmacologic treatment algorithms and guidelines for severe personality disorder. Objective: We evaluated studies on the effectiveness of psychoactive drugs on specific symptom domains for borderline and/or schizotypal personality disorder. Data sources: The literature was searched for placebo-controlled randomized clinical trials (PC-RCTs) on the effectiveness of psychopharmacologic drugs in personality disorder patients. The PubMed, PsychINFO, PiCarta, Cochrane, and Web of Science databases were searched using the search terms borderline personality, schizotypal personality, personality disorder, cluster A, cluster B, treatment, drug, pharmacotherapy, antipsychotic, antidepressant, mood stabilizer, effect, outcome, review, and meta-analysis for studies published between 1980 and December 2007, and references were identified from bibliographies from articles and books. Study selection: Placebo-controlled randomized clinical trials on the efficacy of antipsychotics, antidepressants, and mood stabilizers regarding cognitive-perceptual symptoms, impulsive-behavioral dyscontrol, and affective dysregulation (with subdomains depressed mood, anxiety; anger, and mood lability) were selected in patients with well defined borderline and/or schizotypal personality disorder. Studies whose primary emphasis was on the treatment of Axis I disorders were excluded. Meta-analyses were conducted using 21 retrieved studies. Results: Antipsychotics have a moderate effect on cognitive-perceptual symptoms (5 PC-RCTs; standardized mean difference [SMD] = 0.56) and a moderate to large effect on anger (4 PC-RCTs; SMD = 0.69). Antidepressants have no significant effect on impulsive-behavioral dyscontrol and depressed mood. They have a small but significant effect on anxiety (5 PC-RCTs; SMD = 0.30) and anger (4 PC-RCTs; SMD = 0.34). Mood stabilizers have a very large effect on impulsive-behavioral dyscontrol (6 PC-RCTs; SMD = 1.51) and anger (7 PC-RCTs; SMD = 1.33), a large effect on anxiety (3 PC-RCTs; SMD = 0.80), but a moderate effect on depressed mood (5 PC-RCTs; SMD = 0.55). Mood lability as an outcome measure was seldomly assessed. Mood stabilizers have a more pronounced effect on global functioning (3 PC-RCTs; SMD = 0.79) than have antipsychotics (5 PC-RCTs; SMD = 0.37). The effect of antidepressants on global functioning is negligible. Conclusions: Drug therapy tailored to well-defined symptom domains can have a beneficial effect on patients with severe personality disorder. The findings from this study raise questions on current pharmacologic algorithms. J Clin Psychiatry 2010,71(1):14-25 (C) Copyright 2010 Physicians Postgraduate Press, Inc

Background: Preconception carrier screening for hemoglobinopathies (HbPs) is debated in the Netherlands. Objectives: Intentions to participate in preconception carrier screening for HbPs as well as informed reproductive options were assessed in 109 Turkish female immigrants. Method: Participants completed a structured questionnaire. Results: 83.5% of 109 Turkish female immigrants intended to participate in preconception carrier screening. Intention to participate was related to the desire to reduce uncertainty about having offspring affected by HbPs, but not with socio-demographic variables, risk-estimation and worrying. If the tests concerning carrier status for HbPs were confirmative for both partners, 36.3% (n = 33) of the women with the intention of preconception carrier screening would refrain from getting children of their own, including 14.3% (n = 13) opting for adoption, 37.4% (n = 34) would decide to become pregnant and to opt for prenatal testing on HbPs. Finally, among 37.4% of the women opting for prenatal testing, 30.3% (n = 10) would terminate an affected pregnancy, 18.2% (n = 6) not and 51.5% (n = 17) could not decide (1 missing value). Conclusion: A large majority of Turkish female immigrants would participate in preconception carrier screening for HbPs.

There were two objectives of this research. First was to establish the utility of online digital assistance (ODA), a generic software-based method designed to support behavioral training (BT) in migraine. The second was to test whether ODA can produce additional effects in BT. Utility (feasibility and acceptability) was based on 44 patients with migraine who received ODA as an adjuvant to BT delivered to small groups by lay trainers with migraine at home. ODA tracking files were used to determine ODA feasibility. Acceptability was assessed by a structured interview. To examine ODA effects, 31 patients with migraine who received ODA during BT and at 6 months' follow-up were compared with a matched group of 31 participants who received BT only. Feasibility was established based on minimal technical problems, good compliance, and successful execution of ODA. Acceptability was confirmed by positive participant responses concerning usefulness, supportiveness, and low burden. Finally, ODA participants did not mark better improvements considering migraine attack frequency, internal control, and migraine-specific quality of life compared to those that underwent BT only. ODA is feasible, well-accepted, and perceived to support self-care in 44 patients with migraine. The method is currently designed for these patients, but it can be easily adapted for other health settings. Whether ODA can induce higher gains remains to be established.

In a large retail business group the ID Migraine Screening Test was sent to employees with three or more absences from work in the past year ( n = 2893). Employees with positive results were invited for a neurological consultation and migraine patients were randomly assigned to: first attack ‘treated as usual’ and the second attack treated with 40 mg eletriptan, or reversed order. Of the 2893 employees, 799 responded (28%), 260 were positively screened for migraine (33%), 84 patients were diagnosed by a neurologist and 41 of the 75 included patients completed the protocol. Eletriptan induced pain-free response in 33.3% of the patients at 4 h compared with 0% after ‘non-specific’ treatment ( P = 0.03). Eletriptan also significantly improved quality of life, but differences in absence from work and productivity loss could not be detected. In conclusion, in-company screening can be beneficial for undertreated employees, but implementation obstacles can reduce the effectiveness of screening.

Knowledge on the quality of life of children with headache is lacking. Until now only a few studies in this field have provided information on a limited number of life domains. The aim of this study was to assess the quality of life in a comprehensive number of life domains in children with primary headache presenting at an out-patient paediatric department in a general hospital. From October 2003 to October 2005 all children referred to the out-patient paediatric department of the Vlietland Hospital because of primary headache were investigated by protocol. A thorough history was taken and a general physical and neurological examination was performed. The International Headache Society criteria were used for classification. Quality of life (QoL) was measured using the Dutch version of the Child Health Questionnaire (CHQ-PF50 Dutch edition) and compared with data from a previously investigated cohort of healthy children from the same region, and with data from a cohort of children from the USA with asthma or with attention deficit hyperactivity disorder (ADHD), investigated with the CHQ-PF50. A total of 70 primary headache patients were included in the study (25 with tension-type headache, 36 with migraine, seven with chronic tension-type headache, two with both tension-type headache and migraine). Their mean age was 10.6 years (range 4–17 years); 37 children were male. On all but one subscale (self-esteem) the QoL of the children with primary headache was decreased compared with the cohort of healthy children, especially on the domains of mental health, parental impact time and family cohesion. Compared with the cohort of children with asthma the QoL was significantly worse for our headache group on seven subscales and significantly better on one subscale (general health perception). Compared with the cohort of children with ADHD, the QoL was significantly worse on six subscales but significantly better on three subscales. There were no significant differences on any QoL subscale between children with tension-type headache and children with migraine. We conclude that the QoL in children with primary headache presenting at the out-patient paediatric department of a general hospital seems to be considerably diminished. Furthermore, we conclude that, in this population there is no difference in QoL between children with tension-type headache and those with migraine.

In Europe, living kidney donation rates differ considerably from country to country. These differences are related to deceased kidney donation rates: countries with higher deceased donation rates have lower living donation rates. Despite the differences, all Countries have one thing in common, namely, the shortage of kidneys for transplantation. Living kidney donation is a good option to alleviate these shortages. In our center, 60% to 70% of all kidney transplants come from living donors. This article describes various strategies that may have contributed to these high living donation rates: learn attitude, educational materials and meetings, and alternative donation programs (exchange donation, domino-paired donation, Good Samaritan donation). Also described are some less conventional strategies for increasing rate of living kidney donation that are not used in the Netherlands but may offer some good perspectives (eg, the "Norwegian approach" and home-based educational programs). (Progress in Transplantation. 2009; 19:71-75)

Objective: To examine the prognostic value of coping strategies of patients after stroke at time of discharge on quality of life approximately one year later. In addition, we estimated the maximum cost of improving quality of life by enhancing coping strategies using strict assumptions.Methods: Eighty patients with a stroke completed several questionnaires, at discharge to home and 9-12 months later (follow-up). Questionnaires measured quality of life, coping strategies Tenacious Goal Pursuit and Flexible Goal Adjustment. First, a regression analysis was carried out predicting quality of life at follow-up from coping strategies at discharge. Secondly, a maximum in terms of acceptable cost was calculated for several possible effect sizes.Results: Both coping strategies at discharge were positively associated with quality of life at follow-up. With regards to cost-effectiveness, a medium effect size would result in an increase in quality of life of approximately 10%. The maximum acceptable cost of an intervention for a single patient is therefore set at (sic)2500, assuming a benefit of one year and a cost per quality adjusted life year of (sic)25,000.Conclusion: Coping strategies at discharge are predictive of quality of life one year later. The costs of improving quality of life are thought to be within the limits that determine a cost-effective intervention.

Objective: To examine the association of parent behavior with infant distress during a potentially painful medical procedure. A second aim was to investigate the association of parent chronic pain and psychological problems with parent behavior and infant distress during the procedure. Design: Population-based cohort study with both cross-sectional and prospective measurements. Main Outcome Measures: Video recordings of 275 parents and their 14-month-old infant undergoing venipuncture were coded with an observational instrument to yield measures of infant distress behaviors and parent behaviors, such as reassuring, showing empathy, praising, and distracting. Parent chronic pain and psychological problems were assessed through questionnaires. Results: Infants cried 58% of procedure duration. Parent reassuring occurred 34% of procedure duration, and parent distracting occurred 37% of procedure duration. Infant distress was positively related to parent reassuring and negatively related to parent praising. Parent chronic pain was related to increased parent distracting but not to parent reassuring. Parent psychological problems were not associated with parent behavior and infant distress. Conclusion: Parent behavior rather than psychological traits is related to increased venipuncture distress in young infants. This finding suggests that the focus should be on interventions based on behavior modification.

Data on the experiences of relatives during continuous palliative sedation are scarce. Because these relatives may be the ones most closely involved with the patient, it is important to evaluate the possible burdens that they experience. We aimed to explore and evaluate concerns of relatives during continuous palliative sedation of their family members admitted to an acute palliative care unit. Through retrospective multidisciplinary record research, we obtained data on concerns of the relatives during the period that continuous palliative sedation took place. From October 2001 to October 2004, 45 patients died after starting continuous palliative sedation. In 51% of the cases, the relatives expressed concerns after starting the therapy. Concerns could be distinguished into three main themes: concerns about the aim of continuous palliative sedation (27%), concerns related to the well-being of the patient (29%), and concerns related to the well-being of relatives themselves (18%). Patient and sedation characteristics did not differ significantly between sedations in which relatives did and did not express concerns, except for the duration of the sedation. The median duration of the continuous palliative sedation when concerns were expressed was 46 hours, compared with 19.5 hours when this was not the case (P < 0.05). Both the nature and extent of the concerns suggest that relatives are in need of continuous information and professional guidance during continuous palliative sedation of their family members. Availability of caregiver guidance and clear process documentation are crucial and indispensable in providing this. J Pain Symptom Manage 2009;38:452-459. (C) 2009 U.S. Cancer Pain Relief Committee. Published. by Elsevier Inc. All rights reserved.

Aim: To analyse psychological causes for low compliance with occlusion therapy for amblyopia. Method: In a randomised trial, the effect of an educational programme on electronically measured compliance had been assessed. 149 families who participated in this trial completed a questionnaire based on the Protection Motivation Theory after 8 months of treatment. Families with compliance less than 20% of prescribed occlusion hours were interviewed to better understand their cause for non-compliance. Results: Poor compliance was most strongly associated with a high degree of distress (p < 0.001), followed by low perception of vulnerability (p = 0.014), increased stigma (p = 0.017) and logistical problems with treatment (p = 0.044). Of 44 families with electronically measured compliance less than 20%, 28 could be interviewed. The interviews confirmed that lack of knowledge, distress and logistical problems resulted in non-compliance. Conclusion: Poor parental knowledge, distress and difficulties implementing treatment seemed to be associated with non-compliance. For the same domains, the scores were more favourable for families who had received the educational programme than for those who had not.

Objective: Kidney transplantation with a living donor has proved to be an effective solution for kidney patients on the waiting list for transplantation. Nevertheless, it may be difficult to find a living kidney donor. The purpose of this explorative study is to investigate how kidney transplant candidates may, or may not, find a living donor in the Netherlands. Methods: We compared a group of 42 patients who did not find a living donor with a group of 42 patients who did, using semi-structured interviews. Results: We found that, although almost all patients recognized the advantages of living kidney donation and were willing to accept the offer of a living kidney donor, many found it very difficult to ask a potential donor directly. This was true for both groups. Conclusion: Patients may gain from professional support to deal with this situation in ways that balance their medical needs and their personal relationships. Practice Implications: Support programs should be developed to assist patients in developing strategies for discussing living kidney donation with potential donors. (c) 2008 Elsevier Ireland Ltd. All rights reserved.

Background: Chronic abdominal pain (CAP) or recurrent abdominal pain is common in childhood and is rarely associated with organic disease. With modern diagnostic technology, new organic abnormalities are found in children with CAP. Thus far a causal relation between these abnormalities and CAP has not been established. The additional prognostic value of extensive testing of children with CAP is a subject of debate. Objectives: To investigate how often abdominal pain persists in children with CAP and to investigate whether medical tests such as laboratory tests, imaging, and endoscopy have additional prognostic value to history taking and clinical examination. Materials and Methods: A systematic search was conducted in MEDLINE, EMBASE, and PsycINFO for prospective cohort studies published from 1960 until October 2005. The most common medical key words for CAP were used in our search strategy. The methodological quality of studies was determined. Clinical heterogeneity between studies was analyzed. The percentages of children with abdominal pain after follow-up were pooled. Results: The search yielded 2620 citations, of which 18 studies met the inclusion criteria. In total, 1331 children were followed up for 5 years (median, range 1-29 years). In total, 29.1% (95% CI 28.1-30.2) of patients with CAP had abdominal pain after follow-up. The prognosis of CAP diagnosed clinically was similar to that diagnosed after additional medical testing. Conclusions: CAP persisted in 29.1% (95% CI 28.1-30.2) of children. In the absence of alarming symptoms, additional diagnostic testing did not influence the prognosis of CAP.

Objective.— To evaluate the changes at 6-month follow-up after a home-based behavioral training (BT) provided by lay trainers with migraine to small groups of fellow patients. Background.— The need for self-management programs and cost-effective treatments gave rise to this study. Methods.— In a previous randomized controlled trial, we compared the BT group with a waitlist-control group, receiving usual care. The control group was trained directly after their waitlist period. The present study examined the follow-up results in both groups and measurements were held pre BT, post BT, and at 6-month follow-up. Results.— Six months after BT, 42% was categorized as responders (≥−50% decrease in attack frequency), 42% did not change (−49 to 49%), and 16% responded adversely (≥50% increase). In the group as a whole (n = 95), attack frequency significantly decreased from 3.0 attacks at baseline to 2.5 post BT and to 2.3 at 6-month follow-up (−23%, medium effect size 0.6). The strong improvements of perceived control over and self-confidence in attack prevention were maintained at follow-up. Disability and health status were unchanged but quality of life significantly improved over time (P = .007). BT was more beneficial for patients who entered the training with a high attack frequency. Linear regression analysis demonstrated that a stronger belief at baseline that the occurrence of migraine is due to chance (external control) significantly predicted a lower attack frequency at follow-up. Conclusion.— Lay trainers with migraine can train small groups of fellow patients at home in behavioral attack prevention. At 6-month follow-up, attack frequency and quality of life were significantly but modestly improved and feelings of control and self-confidence remained strongly improved.

Background: High levels of continuous neck pain after a motor vehicle accident (MVA) are reported in cross-sectional studies. Knowledge of this association in general practice is limited. Aim: To compare the differences in perceived pain and disability in patients with acute neck pain due to an MVA versus other self-reported causes. The secondary aim was to identify prognostic factors for continuous neck pain. Design of study: Prospective cohort study with 1-year follow-up. Setting: General practices in Rotterdam and its suburban region. Method: Patients with non-specific acute neck pain were invited to participate. Questionnaires were collected at baseline and after 6,12, 26, and 52 weeks. The numerical pain-rating scale (NRS) and the neck disability index (NDI) were measured. Regression analysis was used to identify prognostic factors for continuous neck pain. Results: A total of 187 patients were included. The MVA subgroup (n = 42) was significantly younger (P = 0.007), reported more sick leave (P = 0.037), higher levels of headache (P

BACKGROUND: Psychological variables, such as anxiety and depression, may have a negative impact on IVF outcomes, but the evidence remains inconclusive. Previous studies have usually measured a single psychological parameter with clinical pregnancy as the outcome. The objective of the current study was to determine whether pretreatment or procedural psychological variables in women undergoing a first IVF cycle affect the chance of achieving a live birth from that cycle. METHODS: Between February 2002 and February 2004, 391 women with an indication for IVF were recruited at two University Medical Centres in The Netherlands. Pretreatment anxiety and depression were measured with the Hospital Anxiety and Depression Scale. The Daily Record Keeping Chart was used to measure negative and positive affect before treatment and daily during ovarian stimulation. Multiple stepwise forward logistic regression analysis was performed with term live birth as the dependent variable. RESULTS: Regression analysis showed that women who expressed less negative affect at baseline were less likely to achieve live birth (P = 0.03). After one IVF cycle, women who received a standard IVF strategy were more likely to reach live birth delivery than those who received a mild IVF strategy (P = 0.002). A male/female indication for IVF was associated with a higher chance of achieving term live birth than a female only indication (P = 0.03). Age, duration of infertility or type of infertility were not independent predictors of live birth. CONCLUSIONS: The relationship between psychological parameters and IVF success rates is more complex than commonly believed. The expression of negative emotions before starting IVF might not be always detrimental for outcomes.

BACKGROUND: Failure of IVF treatment after a number of cycles can be devastating for couples. Although mild IVF strategies reduce the psychological burden of treatment, failure may cause feelings of regret that a more aggressive approach, including the transfer of two embryos, was not employed. In this study, the impact of treatment failure after two or more cycles on stress was studied, following treatment with a mild versus a standard treatment strategy. METHODS: Randomized controlled two-centre trial (ISRCTN35766970). Women were randomized to undergo mild ovarian stimulation (including GnRH antagonist co-treatment) and single embryo transfer (n 5 197) or standard GnRH agonist long-protocol ovarian stimulation with double embryo transfer (n 5 194). Participants completed the Hospital Anxiety and Depression Scale prior to commencing treatment and 1 week after the outcome of their final treatment cycle was known. Data from women who underwent two or more IVF cycles were subject to analysis (n 5 253). RESULTS: Women who experienced treatment failure after standard IVF treatment presented more symptoms of depression 1 week after treatment termination compared with women who had undergone mild IVF: adjusted mean (+ +95% confidence interval)510.2 (+2.3) versus 5.4 (+1.8), respectively, P 5 0.01. CONCLUSIONS: Failure of IVF treatment after a mild treatment strategy may result in fewer short-term symptoms of depression as compared to failure after a standard treatment strategy. These findings may further encourage the application of mild IVF treatment strategies in clinical practice.

Most studies on health related quality of life (HRQoL) of chronic liver patients were done in small clinical populations or restricted to one aetiology or disease stage. There is still a need for a study in a large liver patient population with various aetiologies and disease stages, approaching a population-based study. We evaluated the impact of liver disease aetiology on generic HRQoL, disease-specific HRQoL and fatigue and we compared HRQoL and fatigue between aetiological groups and healthy Dutch controls. Members of the Dutch liver patient association completed the Liver Disease Symptom Index, Short Form-36, and Multidimensional Fatigue Index-20. We compared the HRQoL between patients with viral hepatitis, autoimmune hepatitis, cholestatic diseases, hemochromatosis and other liver diseases by linear, ordinal and logistic regression, corrected for disease stage and other significant factors. Viral hepatitis patients showed a worse mental health than other aetiological groups. Hemochromatosis patients demonstrated 17% more bodily pain than viral hepatitis patients and the strongest decrease in role emotional health with increasing age. Aetiological groups showed a worse generic HRQoL and more fatigue than controls. In conclusion, viral hepatitis and hemochromatosis patients have a more impaired HRQoL than patients of other liver disease aetiological groups.

Background: Quality of life (QoL) is reduced for stroke patients and coping strategies have been suggested as determinants of QoL. Thus far the relationship between coping and QoL has only been examined in small-scale cross-sectional designs. Therefore, the current study set out to examine this relationship in a longitudinal setting. Methods: Stroke patients who were discharged home were interviewed at 4 different time points; just before discharge (T1), and 2 months (T2), 5 months (T3) and 9–12 months after discharge (T4). QoL was measured by the EQ-5D index score and the SF-36 utility score and coping expressed in terms of tenacious goal pursuit and flexible goal adjustment. Modified Rankin scale was assessed as a measure of general functioning. Results: Eighty stroke patients were included. Coping was not predictive of QoL at T1 and T2 but rather at T3 and T4. At T4 both coping strategies determined the levels of QoL as measured with the EQ-5D index score; higher levels of tenacious goal pursuit as well as flexible goal adjustment were associated with higher levels of QoL. This regression model explained 44% of the variance. Conclusions: Coping is a powerful determinant of QoL, but only more than 5 months after discharge; before this time QoL is mainly determined by general functioning. Both coping strategies were important determinants of QoL.

Microglial activation has been linked with deficits in neuronal function and synaptic plasticity in Alzheimer's disease (AD). The mitochondrial translocator protein (TSPO) is known to be upregulated in reactive microglia. Accurate visualization and quantification of microglial density by PET imaging using the TSPO tracer [(11)C]-R-PK11195 has been challenging due to the limitations of the ligand. In this study, it was aimed to evaluate the new TSPO tracer [(11)C]PBR28 as a marker for microglial activation in the 5XFAD transgenic mouse model of AD. Dynamic PET scans were acquired following intravenous administration of [(11)C]PBR28 in 6-month-old 5XFAD mice and in wild-type controls. Autoradiography with [(3)H]PBR28 was carried out in the same brains to further confirm the distribution of the radioligand. In addition, immunohistochemistry was performed on adjacent brain sections of the same mice to evaluate the co-localization of TSPO with microglia. PET imaging revealed that brain uptake of [(11)C]PBR28 in 5XFAD mice was increased compared with control mice. Moreover, binding of [(3)H]PBR28, measured by autoradiography, was enriched in cortical and hippocampal brain regions, coinciding with the positive staining of the microglial marker Iba-1 and amyloid deposits in the same areas. Furthermore, double-staining using antibodies against TSPO demonstrated co-localization of TSPO with microglia and not with astrocytes in 5XFAD mice and human post-mortem AD brains. The data provided support of the suitability of [(11)C]PBR28 as a tool for in vivo monitoring of microglial activation and assessment of treatment response in future studies using animal models of AD.

Introduction In paediatric research, there is a tension between what you can ask from a child and what is needed for the development of evidence-based treatments. To find an optimal balance in conducting clinical research and protecting the child, it is necessary to have empirical data on children9s experiences. Until now, there are scarce empirical data on the experiences from the perspective of the child. In this manuscript, we describe the protocol of a two-phase study measuring children9s self-reported experiences during research procedures. Methods and analysis In the first phase of our study, we aim to interview approximately 40 children (6–18 years) about their self-reported experiences during research procedures. In the second phase, we will develop a questionnaire to measure children9s experiences during research procedures in a quantitative way. We will use the interview outcomes for the development of this questionnaire. Next, we will measure the experiences of children during seven research procedures with this questionnaire. A one-month follow-up is conducted to investigate the emotional impact of the research procedures on the children. Children will be recruited from different research studies in three academic children9s hospitals in the Netherlands. Ethics and dissemination The ethics committee of the VU University medical center evaluated both studies and indicated that there was no risk/discomfort associated, stating that both phases are exempt from getting approval under the Dutch Law. Dissemination of results will occur by conference presentations and peer-reviewed publications. The findings of our project can help Institutional Review Boards and paediatric researchers when evaluating the discomforts of research procedures described in study protocols or when designing a study. Information on experiences of children involved in previous studies may also help children and parents in future research with their decision-making about participation in clinical research, or parts thereof.

Introduction: There is little empirical evidence on children's subjective experiences of discomfort during clinical research procedures. Therefore, Institutional Review Boards have limited empirical information to guide their decision-making on discomforts for children in clinical research. To get more insight into what children's discomforts are during clinical research procedures, we interviewed a group of children on this topic and also asked for suggestions to reduce possible discomforts. Materials and methods: Forty-six children (aged 6-18) participating in clinical research studies (including needle-related procedures, food provocation tests, MRI scans, pulmonary function tests, questionnaires) were interviewed about their experiences during the research procedures. Thematic analysis was used to analyze the interviews. Results: The discomforts of the interviewed children could be divided into two main groups: physical and mental discomforts. The majority experienced physical discomforts during the research procedures: pain, shortness of breath, nausea, itchiness, and feeling hungry, which were often caused by needle procedures, some pulmonary procedures, and food provocation tests. Mental discomforts included anxiousness because of anticipated pain and not knowing what to expect from a research procedure, boredom and tiredness during lengthy research procedures and waiting, and embarrassment during Tanner staging. Children's suggestions to reduce the discomforts of the research procedures were providing distraction (e.g. watching a movie or listening to music), providing age-appropriate information and shortening the duration of lengthy procedures. Discussion: Our study shows that children can experience various discomforts during research procedures, and it provides information about how these discomforts can be reduced according to them. Further research is needed with larger samples to study the number of children that experience these mentioned discomforts during research procedures in a quantitative way. (C) 2015 Elsevier Ltd. All rights reserved.

This review focuses on the effectiveness of short-term behavioural interventions for treating migraine and migraine Regular with tension type headache. The databases of Pubmed and PsycINFO were used to search for studies in which types of Minimal Contact Treatment (MCT) were compared with a standard clinically-based format, pharmacological treatment, or a waiting-list control group. Five studies were selected and judged on their methodological quality based on criteria for clinical trials. These studies showed that MCT is as effective as standard clinically-based treatment, and the efficacy of MCT is much greater than no treatment. In addition, the cost-effectiveness of MCT was substantially higher. Nevertheless, the results are not unambiguous, as few studies fulfilled the methodological criteria and the drop-out rate at follow-up was high. However, MCT can be an interesting method for clinical use, since it is a short, broadly accessible and cost-effective method. Randomized controlled studies on the clinical utility of MCT are needed. The use of treatment partly through the Internet might be considered a promising alternative.

Verhagen AP, Damen L, Bruijn JKJ, Berger MY, Passchier J, Koes BW. Effectiveness of interventions in children with migraine. Huisarts Wet 2006;49(3):123-9. Objective To assess the effectiveness and tolerance of treatment methods for episodes of migraine in children. Methods We performed a systematic review. Databases were searched from inception to June 2004, and references were checked. We selected randomised and controlled trials reporting the effects of symptomatic and prophylactic treatment methods in children with migraine, using headache features as outcome measure. Two independent reviewers assessed trial quality and extracted data. Quantitative and qualitative analyses were carried out according to type of intervention. Results A total of 49 trials (total 3296 patients) were included in this review, of which 16 studies (32.7%) were considered to be of high quality. Ten studies evaluated the effectiveness of acute medication. Compared to placebo, headache improved significantly for acetaminophen, ibuprofen, and nasal sumatriptan. No significant differences were found between acetaminophen and ibuprofen or nimesulide, and between oral sumatriptan, rizatriptan and dihydroergotamine compared to placebo. All medications were well tolerated, but significantly more adverse events were reported for nasal sumatriptan. Nineteen studies evaluated the effectiveness of non-pharmacological prophylactic treatments. When compared to waiting list control, headache improved significantly for relaxation, relaxation plus biofeedback, and relaxation plus biofeedback plus cognitive behavioural treatment. There is conflicting evidence regarding the use of oligoantigenic diets. Lastly, 20 studies evaluated the effectiveness of pharmacological prophylactic treatments. Compared to placebo, headache improved significantly for flunarizine medication. There is conflicting evidence for the use of propranolol. Nimodipine, clonidine, L-5HTP, trazodone and papaverine showed no efficacy when compared to placebo. Conclusions Acetaminophen and ibuprofen are effective symptomatic pharmacological treatments of episodes of migraine in children. Nasal spray sumatriptan is also effective, but more side effects are reported. A few treatments, such as relaxation and flunarizine, may be effective as prophylactic treatment for migraine in children.

BACKGROUND: The objective of this study was to assess the psychological implications of mild ovarian stimulation combined with single embryo transfer (SET) during a first IVF cycle. METHODS: We conducted a randomized controlled two-centre trial. Three hundred and ninety-one couples were randomized to undergo either mild ovarian stimulation with GnRH antagonist co-treatment and SET (n=199) or conventional GnRH agonist long protocol ovarian stimulation with double embryo transfer (DET) (n=192). Women completed the Hospital Anxiety and Depression Scale, the Hopkins Symptom Checklist and the Subjective Sleep Quality Scale at baseline, on the first day of ovarian stimulation and following embryo transfer. Affect was assessed daily with the Daily Record Keeping Chart from the first day of ovarian stimulation until the day treatment outcome became known. RESULTS: The conventional IVF group experienced elevated levels of physical and depressive symptoms during pituitary downregulation. At oocyte retrieval, this group experienced more positive affect and less negative affect than the mild IVF group. In the conventional IVF group, cycle cancellation was associated with less positive and more negative affect. CONCLUSIONS: During the first IVF treatment cycle, mild ovarian stimulation and SET does not lead to more psychological complaints than conventional IVF.

We aimed to assess the effectiveness of conservative treatments in children with tension–type headaches (TTH). We searched Medline, Embase and the Cochrane Library and performed reference checking. Two independent authors assessed trial quality and extracted data. Analysis was carried out according to type of intervention. In total we included 11 trials (427 TTH patients, age between 7–18 years) in this review. None of the studies were considered to be of high quality. Eight studies evaluated the effectiveness of relaxation training. Four studies included a waiting list or no treatment control group and in one study a placebo was used. We found conflicting evidence about the effectiveness of relaxation therapy when compared with no treatment or other treatments, with Relative Risks varying from 1.4 (0.6–3.2) to 10.6 (1.6–71.3). With regard to all other interventions evaluated (such as biofeedback, cognitive therapy or flupirtin) no evidence is found for or against their effectiveness.

Objective. Treatment of pediatric migraine includes an individually tailored regimen of both nonpharmacologic and pharmacologic measures. The mainstay of symptomatic treatment in children with migraine is intermittent oral or suppository analgesics, but there is no coherent body of evidence on symptomatic treatment of childhood migraine available. The objective of this review is to describe and assess the evidence from randomized and clinical controlled trials concerning the efficacy and tolerability of symptomatic treatment of migraine in children. Design. Systematic review according to the standards of the Cochrane Collaboration. Methods. Databases were searched from inception to June 2004. Additional reference checking was performed. Two authors independently selected randomized and controlled trials evaluating the effects of symptomatic treatment in children ( Results. A total of 10 trials were included in this review, of which 6 studies were considered to be of high quality. The number of included participants in each trial ranged from 14 to 653, with a total of 1575 patients included in this review. Mean dropout rate was 19.8% (range: 0–39.1%), and the mean age of participants was 11.7 ± 2.2 years (range: 4–18 years). All studies used HA diaries to assess outcomes. In most studies, a measure of clinical improvement was calculated by using these diaries. Improvement often was regarded as being clinically relevant when the patients' HA declined by ≥50%. Regarding oral analgesic treatment, the effectiveness of acetaminophen, ibuprofen, and nimesulide were evaluated. When compared with placebo, acetaminophen (relative risk [RR]: 1.5; 95% confidence interval [CI]: 1.0–2.1) and ibuprofen (pooled RR: 1.5; 95% CI: 1.2–1.9) significantly reduced HAs. We conclude that there is moderate evidence that both acetaminophen and ibuprofen are more effective in reduction of symptoms 1 and 2 hours after intake than placebo with minor adverse effects. No clear differences in effect were found between acetaminophen and ibuprofen or nimesulide. Regarding the nonanalgesic interventions, nasal-spray sumatriptan, oral sumatriptan, oral rizatriptan, oral dihydroergotamine, intravenous prochlorperazine, and ketorolac were evaluated. When compared with placebo, nasal-spray sumatriptan (pooled RR: 1.4; 95% CI: 1.2–1.7) seemed to significantly reduce HAs. We conclude that there is moderate evidence that nasal-spray sumatriptan is more effective in reduction of symptoms than placebo but with significantly more adverse events. No differences in effect were found between oral triptans and placebo. All medications were well tolerated, but significantly more adverse events were reported for nasal-spray sumatriptan compared with placebo. We also conclude that there is moderate evidence that intravenous prochlorperazine is more effective than intravenous ketorolac in the reduction of symptoms 1 hour after intake. No differences in effect were found between oral dihydroergotamine and placebo. Conclusions. Acetaminophen, ibuprofen, and nasal-spray sumatriptan are all effective symptomatic pharmacologic treatments for episodes of migraine in children. The new frontier for symptomatic treatment is likely to be the development of triptan agents for use in children. Most treatments have only been evaluated in 1 or 2 studies, which limits the generalizability of the findings. We strongly recommend performing a large, high-quality randomized, controlled trial evaluating different symptomatic medications compared with each other or to placebo treatment. Favorable high-quality studies should be performed and reported according to the CONSORT statement. Clinical improvement of HA should be used as the primary outcome measure, but quality of life, days missed at school, and satisfaction of child or parents should also be used as an outcome measure in future studies.

Instruments for measuring pain-related problems in adolescents with chronic pain are sparse, especially those based on the personal experiences of these adolescents. This study aimed to develop and test such an instrument, the pain-related problem list for adolescents (PPL). A sample of 129 adolescents with chronic pain without documented physiological etiology completed the 57-item problem list, which was based on interviews with a similar group of adolescents with chronic pain. Principal components analysis yielded four domains: problems related to (1) concentration; (2) mobility; (3) adaptability; and (4) mood. The questionnaire was shortened to 18 items and has good reliability (total alpha = 0.82; concentration alpha = 0.86; mobility alpha = 0.77; adaptability alpha = 0.71; and mood alpha = 0.78); the validity also proved to be adequate, especially in the general population sample. The PPL provides a tool to assess the impact of chronic pain in adolescents. Future research should focus on further validation of the PPL in a large clinical population and establishing its test-retest reliability.

SYNOPSIS There are few findings of increased stress responses of the vascular system and the (head) muscles in migraine and tension headache patients. However, several studies ignored the headache state of the patients during the experiment and differences in sex, or used small experimental groups. In this controlled study, physiological parameters in migraine patients, tension headache patients and non-headache controls were investigated during conditions of stress and rest. Each group was composed of at least 25 subjects. Sex was included as an independent variable, and separate analyses were carried out on patients with pain during the measurements. There were no differences in vascular responding nor in muscular responding to stress between migraine patients, tension headache patients and controls. Male migraine patients showed enhanced activity in some indicators of sympathetic activity. No evidence was found for a discrete border separating the two headache types.

Objective: The purpose of this article is to provide clinicians who are involved in the field of foetal medicine with a comprehensive overview of theories that are relevant for the parental decision-making process after ultrasound diagnosis of a serious foetal abnormality. Methods: Since little data are available of parental decision-making after ultrasound diagnosis of foetal abnormality, we reviewed the literature on parental decision-making in genetic counselling of couples at increased genetic risk together with the literature on general decision-making theories. The findings were linked to the specific situation of parental decision-making after an ultrasound diagnosis of foetal abnormality. Results: Based on genetic counselling studies, several cognitive mechanisms play a role in parental decision-making regarding future pregnancies. Parents often havea binary perception of risk. Probabilistic information is translated into two options: the child will or will not be affected. The graduality of chance seems to be of little importance in this process. Instead, the focus shifts to the possible consequences for future family life. General decision-making theories often focus on rationality and coherence of the decision-making process. However, studies of both the influence of framing and the influence of stress indicate that emotional mechanisms can have an important and beneficial function in the decision-making process. Conclusion: Cognitive mechanisms that are elicited by emotions and that are not necessarily rational can have an important and beneficial function in parental decision-making after ultrasound diagnosis of a foetal abnormality. Consequently, the process of parental decision-making should not solely be assessed on the basis of its rationality, but also on the basis of the parental emotional outcome.

Background. Policies with respect to altruistic living kidney donation to strangers (both nondirected and directed donation) should, in addition to medical criteria, preferably be based on valid attitude research data. However, deciding on what data are relevant is a normative issue. The challenge for both research and policy making is to bring together empirical and normative issues. Methods. By comparing two recent surveys, the authors shed light on the complex methodologic and ethical questions surrounding altruistic living kidney donation. Results. The authors found that the main methodologic issues were the distinction between the willingness to donate and the acceptability of the offer, the difference between public attitudes observed in surveys ("facts") and well-considered moral judgments ("norms"), and biases caused by a misperception of central moral concepts (e.g., discrimination and injustice). The authors argue that transplantation centers have a good case for applying or initiating altruistic living donation programs. Centers should seek to influence public attitudes if these attitudes are shown to be biased by prejudice and misunderstanding. Conclusions. The authors advocate an interaction between research and policy making. Social research can best influence transplantation policies in altruistic living donation by in-depth interviews into the complicated background beliefs underlying personal preferences. In addition, the public should be encouraged to judge the immanent issues in a morally responsible way. In the end, a fair balance should be established between the impartial requirements of social justice and the partial motivations of individuals involved in altruistic living donation. Although discriminatory acts should be rejected categorically, donation policies should be willing to consider, support, and accept motivations based on personal loyalties. Copyright