Management of osteonecrosis of the femoral head in children with sickle cell disease: results of conservative and operative treatments at skeletal maturity.

PURPOSE: Sickle cell disease (SCD) is the most common cause of femoral head osteonecrosis (ONFH) during childhood with an overall prevalence of 10%. In children, spontaneous revascularization can occur, as in Legg-Calve-Perthes disease. Consequently, the aim of treatment is to restore proper hip containment to prevent joint arthritis. This is the first study reporting long-term results at skeletal maturity of non-operative and surgical treatments for ONFH in SCD children. METHODS: All children with ONFH due to SCD were retrospectively reviewed. At initial evaluation, extension of osteonecrosis was radiographically defined using Catterall, lateral pillar Herring and Ficat classifications. Subluxation of the femoral head with Reimers migration index > 30% required surgical treatment including femoral varus osteotomy and/or pelvic osteotomies. Conservative treatment including non-weight bearing and physiotherapy was performed in the remaining cases. Outcomes were assessed at skeletal maturity using the Harris Hip Score (HHS) and the Stulberg classification. Total hip arthroplasty and Stulberg 5 were defined as failures. RESULTS: A total of 25 hips in 17 patients were included (mean follow-up 7.5 years SD 3.4). Mean age at diagnosis was 11.4 years SD 2.9. In all, 15 hips (60%) were classified Catterall 3 and 4 and Herring B and C. A total of 13 patients (52%) underwent surgical treatment. At skeletal maturity, mean HHS was good (81 SD 17), 12 hips (48%) were classified Stulberg 1 and 2, seven hips (28%) were classified Stulberg 3 and 4. CONCLUSION: Both treatments led to good functional results with 75% of congruent hips at skeletal maturity. LEVEL OF EVIDENCE: IV.

Development, content validity, and cross-cultural adaptation of a patient-reported outcome measure for real-time symptom assessment in irritable bowel syndrome.

BACKGROUND: End-of-day questionnaires, which are considered the gold standard for assessing abdominal pain and other gastrointestinal (GI) symptoms in irritable bowel syndrome (IBS), are influenced by recall and ecological bias. The experience sampling method (ESM) is characterized by random and repeated assessments in the natural state and environment of a subject, and herewith overcomes these limitations. This report describes the development of a patient-reported outcome measure (PROM) based on the ESM principle, taking into account content validity and cross-cultural adaptation. METHODS: Focus group interviews with IBS patients and expert meetings with international experts in the fields of neurogastroenterology & motility and pain were performed in order to select the items for the PROM. Forward-and-back translation and cognitive interviews were performed to adapt the instrument for the use in different countries and to assure on patients' understanding with the final items. KEY RESULTS: Focus group interviews revealed 42 items, categorized into five domains: physical status, defecation, mood and psychological factors, context and environment, and nutrition and drug use. Experts reduced the number of items to 32 and cognitive interviewing after translation resulted in a few slight adjustments regarding linguistic issues, but not regarding content of the items. CONCLUSIONS AND INFERENCES: An ESM-based PROM, suitable for momentary assessment of IBS symptom patterns was developed, taking into account content validity and cross-cultural adaptation. This PROM will be implemented in a specifically designed smartphone application and further validation in a multicenter setting will follow.

Rome III functional dyspepsia symptoms classification: Severity vs frequency.

BACKGROUND: The Rome III criteria subdivide functional dyspepsia (FD) in the epigastric pain syndrome (EPS) and the postprandial distress syndrome (PDS) based on the frequency of the symptoms to optimize the diagnostic and therapeutic approach. However, it is unclear to which extent the frequency of the symptoms is related to their severity. Our aim was to explore the frequency and severity of dyspeptic symptoms and their relationship in FD patients. METHODS: Functional dyspepsia patients fulfilling the Rome III diagnostic completed a questionnaire that evaluated the frequency and severity of FD symptoms. The concordance between the severity and frequency categories was analyzed by means of spearman correlation and the concordance correlation coefficient (ρc ). KEY RESULTS: In the entire patient cohort (n=421), the classification of symptoms severity and frequency showed good concordance for all symptoms. In the EPS subgroup (n=….), the symptom severity and frequency score of epigastric pain showed a poor correlation (r=.28; ρc =0.07). The PDS subgroup (n=…) showed a good correlation for most of the symptoms. Due to its limited occurrence in this group, the correlation of the severity and frequency scores for epigastric pain is of little relevance (r=.79; ρc =0.58). The overlap EPS-PDS group showed good correlation for most of the symptoms, except for epigastric pain (pain r=.24; ρc =0.09). CONCLUSIONS & INFERENCES: We conclude that the information given by the assessment of frequency and severity of PDS symptoms is comparable and hence one of the scores sufficiently identifies symptom pattern in PDS patients. In EPS patients, both the symptom frequency and severity should be taken into account as two separate entities.

Validation of the Leuven Postprandial Distress Scale, a questionnaire for symptom assessment in the functional dyspepsia/postprandial distress syndrome.

BACKGROUND: A validated patient-reported outcome instrument is lacking for the functional dyspepsia/postprandial distress syndrome. AIM: To validate the Leuven Postprandial Distress Scale (LPDS). METHODS: The LPDS diary, comprising eight symptoms with verbal descriptors rated for severity (0-4), was derived from focus groups and cognitive debriefing. It was used in a 2-week run-in, 8-week double-blind placebo-controlled trial of itopride 100 mg t.d.s. Results in 60 patients, with concealed treatment allocation, were used to analyse LPDS content validity, consistency, reliability and responsiveness. Patients also filled out Patient Assessment of Gastrointestinal Symptoms (PAGI-SYM), Nepean Dyspepsia Index, overall treatment evaluation and overall symptom severity questionnaires. Construct validity was evaluated by known-group analyses and by correlating LPDS with these additional questionnaires. Minimum Clinically Important Difference was determined from threshold changes in anchor questionnaires. RESULTS: Symptom patterns and factor analysis identified three cardinal symptoms of postprandial distress syndrome (early satiation, postprandial fullness, upper abdominal bloating), whose mean intensities generate weekly LPDS scores. Known-groups analysis showed large-effect-size differences in LPDS scores (Cohen's d = 2.16). Strong correlations (r > 0.57) between LPDS scores and relevant anchors at baseline indicate good convergent validity. Internal consistency of LPDS was good (α > 0.85) with high inter-item correlations (0.67-0.76), and test-retest reliability (r = 0.85). Changes in LPDS scores were highly convergent with changes in overall treatment evaluation, overall symptom severity and PAGI-SYM (r > 0.52). minimum clinically important difference analysis generated thresholds of 0.4-0.6. CONCLUSIONS: The Leuven Postprandial Distress Scale, which is supported by the European Medicines Agency, is a sensitive and reliable patient-reported outcome instrument to assess symptoms in the functional dyspepsia/postprandial distress syndrome.

Rome III functional dyspepsia subdivision in PDS and EPS: recognizing postprandial symptoms reduces overlap.

BACKGROUND: The Rome III consensus proposed to subdivide functional dyspepsia (FD) into two groups: meal-related dyspepsia or postprandial distress syndrome (PDS), and meal-unrelated dyspepsia or epigastric pain syndrome (EPS). However, in clinical practice, overlap between both has been reported to be as high as 50%, thereby hampering clinical applicability. Although EPS is referred to as meal-unrelated dyspepsia, relationship of symptoms to meal ingestion in this category is not formally addressed in the Rome III criteria. The aim of our study was to investigate whether taking into account the relationship of epigastric pain and nausea to meal ingestion may help to improve separation between EPS and PDS. METHODS: Consecutive ambulatory tertiary-care patients with epigastric symptoms filled out Rome III gastro-duodenal questionnaires with supplementary questions. Those fulfilling Rome III FD criteria and a negative endoscopy were identified and subdivided into 'pure' PDS patients (i.e., meeting criteria for PDS without EPS symptoms), 'pure' EPS (i.e., meeting criteria for EPS without PDS symptoms), and overlapping PDS-EPS (i.e., symptoms of both PDS and EPS). KEY RESULTS: Out of 1029 patients coming to endoscopy, 199 patients (73% females, 45.9 ± 1.0 years, BMI: 23.7 ± 0.35) fulfilled Rome III FD diagnostic criteria, and could be subdivided into pure PDS (69% females, 49 ± 2 years, BMI: 24.2 ± 0.61), pure EPS (59% females, 47.4 ± 2 years, BMI: 23.2 ± 0.97) and overlapping PDS-EPS (64% females, age 43 ± 5 years, BMI: 26 ± 0.46). Compared with pure EPS patients, the overlap PDS-EPS patients were characterized by a higher occurrence of postprandial epigastric pain (70% vs 31%, p < 0.0001), while the occurrence of epigastric pain in between meals was borderline (48% vs 38%, p = 0.05). In addition, the overlap PDS-EPS patients reported a higher occurrence of postprandial nausea (23% vs 0%, p < 0.0001), and bloating (79% vs 28%, p = 0.0001). When postprandial epigastric pain and postprandial nausea were considered as PDS symptoms, the 'adapted' subdivision identified 48% pure PDS, 16% pure EPS, and 36% overlapping PDS-EPS patients. CONCLUSIONS & INFERENCES: EPS and PDS symptoms frequently coexist in FD patients, with postprandial symptoms substantially contributing to the overlap. A more rigorous linking of postprandially occurring symptoms to PDS, regardless of their qualitative nature, may improve the separation between PDS and EPS.

Acute chest syndrome after laparoscopic splenectomy in children with sickle cell disease: operative time dependent?

BACKGROUND: Laparoscopic splenectomy remains a technically demanding procedure. On patients with sickle cell disease (SCD), a post operative acute chest syndrome (ACS) can occur. The aim of the study was to look for predictive factors of post operative ACS. PATIENTS AND METHOD: It's a retrospective study on patients with SCD, who underwent a laparoscopic splenectomy in Robert Debré hospital, Paris, France, between March 2008 and December 2013. Diagnosis of ACS was done if the patient developed hypoxemia associated with fever above 38.5 °C and an infiltrate on chest x ray during the post operative course. Pre-, post- and operative factors were studied. Descriptive statistics were compared using the Mann-Whitney test or the exact Fisher test. A p inferior to 0.05 was considered as significant. RESULTS: 52 patients with SCD underwent a laparoscopic splenectomy. Twelve patients presented a post operative ACS (23%) (mean age at surgery 4 years old) while forty did not (mean age 5.25 years old). Neither previous episode of ACS nor any factors reflecting SCD severity were significant. The shorter the operative time was, the greater the risk of developing an ACS (p < 0.05). CONCLUSION: ACS is an important complication following laparoscopic splenectomy in patients with SCD. The immediate post operative management, in the absence of predictive factors for ACS, should be carefully followed in a high dependency unit at least for 48 h for all patients.

Functional dyspepsia: outcome of focus groups for the development of a questionnaire for symptom assessment in patients suffering from postprandial distress syndrome (PDS).

BACKGROUND: To date, no patient reported outcomes (PRO) instrument is available for evaluation of treatment efficacy in functional dyspepsia (FD)/postprandial distress syndrome (PDS). The aim of our study was to perform focus group interviews for the development of a new questionnaire for assessing symptom pattern and severity in PDS. METHODS: Random ambulatory patients diagnosed with FD/PDS based on Rome III criteria and no predominant gastro-esophageal reflux disease (GERD) symptoms were invited to participate. Focus group sessions were organized where patients reported and discussed their symptoms, facilitated by an experienced physician. After reaching saturation of identified symptom items, questions for a pilot PRO instrument were drafted and evaluated in cognitive interviews for relevance, clarity, and consistency. KEY RESULTS: Of 225 screened patients, 26 patients were diagnosed with PDS without overlapping GERD as single final diagnosis. Fifteen of these (87% female, 48 ± 3.2 years) participated in one of three focus groups. All (100%) confirmed experiencing symptoms that were triggered or aggravated by ingestion of a meal, corresponding to early satiation (100%), and postprandial fullness (100%). In addition reported gastroduodenal symptoms were nausea (40%, postprandial in all, interprandial in 20%), upper abdominal bloating (33%), excessive belching (27%), and vomiting (13%). Epigastric pain and burning were present in respectively 20% and 13%. Non-gastroduodenal symptoms that patients reported included heartburn (33%, but mostly sporadic), weight loss (93%, on average 5.0 ± 1.7 kg), and fatigue (67%). Questions evaluating these symptoms were validated in 15 cognitive interviews. CONCLUSIONS & INFERENCES: This focus group study confirms symptoms corresponding to postprandial fullness and early satiation as the key items for developing a PRO for PDS.

The use of pictograms improves symptom evaluation by patients with functional dyspepsia.

BACKGROUND: No validated patient-reported outcome (PRO) measure exists for functional dyspepsia (FD) assessment. Verbal descriptions of different upper abdominal symptoms may be poorly distinguishable to patients. AIM: To investigate whether understanding of FD symptoms is enhanced by pictograms symbolising the nature of the symptoms, besides verbal descriptors. METHODS: Consecutive FD patients were randomised to fill out a questionnaire assessing nineupper gastrointestinal symptoms (post-prandial fullness, early satiation, epigastric pain, epigastric burning, bloating centred in the upper abdomen, nausea, vomiting, heartburn, regurgitation) with or without accompanying pictograms. Symptoms were rated for frequency and severity (0-5), and patients also identified the most bothersome symptom. Subsequently, in-depth history was taken by an expert clinician, who filled out the same symptom ratings. Concordance between patient and clinician ratings was quantified using chi-square and kappa statistics. RESULTS: Content validity of pictograms was first confirmed by 15 FD patients. Next, 76 patients (52 women, age 42.2 ± 1.9) were randomised to questionnaires with or without pictograms. The concordance with clinician's assessment as gold standard rose from 36 without to 48% for questions with pictograms (P < 0.0001). Considering the Rome III subdivision, benefit in concordance with pictograms was present for post-prandial distress, epigastric pain syndrome and reflux symptoms. Kappa statistics confirmed these gains (weighted kappa values for concordance of symptom frequency ratings rose from 0.214 to 0.446 with pictograms), and also showed better concordance of the most bothersome symptom with pictograms. CONCLUSION: Pictograms accompanying verbal descriptors significantly improve concordance of functional dyspepsia symptom ratings by patients with evaluation by their physicians.

A pilot study of the effects of the somatostatin analog pasireotide in postoperative dumping syndrome.

BACKGROUND: Dumping syndrome is characterized by distinct pathophysiological features such as postprandial increase in hematocrit (HT) and pulse rate (PR) and delayed hypoglycemia (HG). Treatment is based on dietary measures and somatostatin analogs (SA), but current SAs have incomplete efficacy, possibly through limited affinity for various somatostatin receptor subtypes. We evaluated the effect of pasireotide, a novel SA with high affinity for 4/5 human somatostatin receptors, on pathophysiological events and symptoms in dumping. METHODS: Randomized double-blind placebo-controlled cross-over study of nine patients (six women, 47 ± 4 years) with postoperative dumping. Baseline measurements included oral glucose tolerance testing (OGTT), abdominal ultrasound, and dumping symptom severity score (DSSS). Patients were treated for 2 weeks with placebo or pasireotide 300 µg s.c. t.i.d. with a 1-week wash-out in a randomized fashion. On day 13 and 14 of each treatment OGTT, DSSS, and solid and liquid gastric emptying (GE) were obtained. KEY RESULTS: Baseline OGTT was pathological in all patients based on PR (n = 5), HT (n = 1) or HG (n = 7). Compared to placebo, pasireotide suppressed the increase in PR (17.1 ± 2.8 vs 8.2 ± 3.5 bpm; p < 0.05) and late HG (nadir glycemia 55.6 ± 4.3 vs 83.3 ± 9.5 mg/dL; p = 0.007), increased peak glycemia (294.1 ± 33.3 vs 221.0 ± 23.1 mg/dL; p = 0.001) and delayed GE of solids (t1/2 83 ± 23 vs 43 ± 9 min; p = 0.05) and liquids (t1/2 70 ± 10 vs 40 ± 4 min, p = 0.05). The differences in DSSS did not reach statistical significance. Two patients dropped out because of adverse gastrointestinal events under pasireotide. CONCLUSIONS & INFERENCES: Pasireotide affects pathophysiological features of both early and late dumping syndrome.

[Development of psychological and intellectual performance in transplanted sickle cell disease patients: a prospective study from pretransplant period to 5 years after HSCT]. / Développement psycho-intellectuel des enfants drépanocytaires ayant reçu une allogreffe de cellules souches hématopoïétiques.

RATIONALE: Allogeneic hematopoietic stem-cell transplantation (HSCT) is the only curative treatment for sickle cell disease (SCD). Cerebral vasculopathy was the principal indication for transplantation. These children could present impaired neuropsychological development related to different causes, hence the value of exploring their intellectual capacities before and after transplantation. MATERIAL AND METHODS: Prospective longitudinal study from 1992 to 2006 in all transplanted SCD patients. The patients were assessed using Wechsler scales with four different indices: verbal comprehension, perceptual reasoning, working memory, and processing speed (PSI), providing a full-scale intellectual quotient (IQ). RESULTS: Fifteen SCD patients (8 females and 7 males; mean age, 8.9 years) were evaluated before and 36 and 60 months after transplantation. All were from Africa and lived in France. All patients except 2 had experienced ischemic stroke before HSCT. The median full-scale IQ was 87, 94, and 94 before transplantation and 36 months and 60 months after HSCT, respectively. DISCUSSION: At pre-HSCT evaluation, full-scale IQ was considered as "low average". This relatively poor result could be related to impairment of PSI, which reflects frequent graphic and motor abnormalities related to the previous stroke experienced by almost all patients. At 3 years after HSCT, all indices including IQ had increased. Only the PSI had decreased, this observation being potentially related to previous stroke and to the depression frequently experienced by the transplant recipient patient after the acute phase, when the disease is cured. At 5 years after HSCT, the median full-scale IQ was stable and the PSI had increased. CONCLUSION: At the end of follow-up, the patients improved their physical and psychological well-being. This allowed them to build projects for the future and to manifest the desire of becoming an adult. Bone marrow transplantation in this cohort of children with SCD and severe cerebral vasculopathy is associated with improved performance as measured by the Wechsler scale.

Associations between gastric sensorimotor function, depression, somatization, and symptom-based subgroups in functional gastroduodenal disorders: are all symptoms equal?

BACKGROUND: Previous work indicated that psychosocial factors (depression and somatization) are more strongly associated with symptom severity and weight loss in functional dyspepsia (FD) than gastric sensorimotor function. However, there is conflicting evidence regarding the association of these etiopathogenetic factors with Rome III symptom-based subgroups in FD [epigastric pain syndrome (EPS), postprandial distress syndrome (PDS)]. We aimed to test whether gastric sensitivity and emptying, depression, and somatization are differentially associated with empirically derived functional gastroduodenal disorders (FGD) symptom factors in one comprehensive model. METHODS: In 259 tertiary care FD patients, we studied gastric sensorimotor function with barostat and gastric emptying breath test. Depression, somatization, and FGD symptoms were measured using self-report questionnaires. Confirmatory factor analysis (CFA) on 7 FGD symptoms was used to determine the fit of a latent variable structure based on Rome III symptom-based subgroups. Structural equation modeling (SEM) was used to test the putative relationships of the symptom factors with gastric sensorimotor function, depression, and somatization. KEY RESULTS: The results of the CFA show a good fit [C(min) /DF = 1.54, CFI(comparative fit index) = 0.97] for the three-factor solution based on Rome III subgroups. The SEM also fitted the data well (C(min) /DF = 1.24, CFI = 0.98) and demonstrated that gastric sensitivity and depression are associated with PDS and nausea and vomiting. Gastric emptying is uniquely associated with EPS and somatization is strongly associated with all three symptom factors. CONCLUSIONS & INFERENCES: Confirmatory factor analysis confirms the existence of three FGD symptom factors, corresponding to Rome III symptom-based subgroups. The SEM results suggest that different psychobiological mechanisms may play a role in these subgroups.

A double-blind sham-controlled study of the effect of radiofrequency energy on symptoms and distensibility of the gastro-esophageal junction in GERD.

OBJECTIVES: Several studies have reported symptom relief in gastro-esophageal reflux disease (GERD) patients treated with radiofrequency delivery (Stretta procedure) at the gastro-esophageal junction (GEJ), but the mechanism underlying this improvement is unclear. The objective of this study was to test the hypothesis that Stretta alters GEJ resistance. METHODS: We conducted a double-blind randomized cross-over study of Stretta and sham treatment. Consecutive GERD patients were included in the study. The study was conducted in a tertiary care center. Patients underwent two upper gastrointestinal endoscopies with 3 months interval, during which active or sham Stretta treatment was performed in a randomized double-blind manner. Symptom assessment, endoscopy, manometry, 24-h esophageal pH monitoring, and a distensibility test of the GEJ were done before the start of the study and after 3 months. RESULTS: Barostat distensibility test of the GEJ before and after administration of sildenafil was the main outcome measure. In all, 22 GERD patients (17 females, mean age 47±12 years) participated in the study; 11 in each group. Initial sham treatment did not affect any of the parameters studied. Three months after initial Stretta procedure, no changes were observed in esophageal acid exposure and lower esophageal sphincter (LES) pressure. In contrast, symptom score was significantly improved and GEJ compliance was significantly decreased. Administration of sildenafil, an esophageal smooth muscle relaxant, normalized GEJ compliance again to pre-Stretta level, arguing against GEJ fibrosis as the underlying mechanism. CONCLUSIONS: The limitation of this study was reflux evaluation did not include impedance monitoring. In this sham-controlled study, Stretta improved GERD symptoms and decreased GEJ compliance. Decreased GEJ compliance, which reflects altered LES neuromuscular function, may contribute to symptomatic benefit by decreasing refluxate volume.

Do we have an alternative for the Rome III gastroduodenal symptom-based subgroups in functional gastroduodenal disorders? A cluster analysis approach.

BACKGROUND: Functional dyspepsia (FD) is a heterogeneous biopsychosocial disorder. The Rome III consensus proposed a subdivision into epigastric pain syndrome and postprandial distress syndrome, based on gastroduodenal symptom pattern only; nausea/vomiting- and belching disorders were classified as separate functional gastroduodenal disorders (FGD). We aimed to investigate an alternative subdivision of FGD, taking into account gastric sensorimotor function, anxiety & depression and 'somatization', besides gastroduodenal symptoms. METHODS: Gastroduodenal symptom data were available for 857 consecutive FGD patients (Rome II criteria). In a subsample (n=259), additional data were obtained on gastric sensitivity, anxiety, depression and 'somatization'. Two separate cluster analyses were performed. In analysis 1, clustering was based on individual gastroduodenal symptom scores. In analysis 2, gastric sensitivity, anxiety & depression and 'somatization', besides total gastroduodenal symptoms score, were used for clustering. KEY RESULTS: Analysis 1 identified four clusters, largely supporting the Rome III classification, with early satiation, pain and nausea/vomiting clusters, besides a limited severity cluster (R(2) = 0.32). Analysis 2 suggested a five-cluster solution (R(2) = 0.48). Anxiety, depression and 'somatization' were the most important variables separating the clusters. 'Primary somatization' (with low psychiatric symptom levels) as well as 'secondary somatization' (with high anxiety & depression scores) subgroups were identified, besides three other subgroups characterized by psychiatric/gastroduodenal symptoms, mild anxiety symptoms and limited overall severity, respectively. CONCLUSIONS & INFERENCES: We propose an alternative to the current subgrouping in FGD that is exclusively based on gastroduodenal symptoms. This may have consequences for future classification of FGD, as well as broader relevance towards the debate on subgrouping 'functional somatic syndromes'.

Factors associated with co-morbid irritable bowel syndrome and chronic fatigue-like symptoms in functional dyspepsia.

BACKGROUND: It is unclear which factors explain the high co-morbidity between functional dyspepsia (FD) and other functional somatic syndromes. The aim of this study is to investigate the association between gastric sensorimotor function, psychosocial factors and 'somatization' on the one hand, and co-morbid irritable bowel syndrome (IBS) and chronic fatigue (CF)-like symptoms on the other, in FD. METHODS: In 259 tertiary care FD patients, we studied gastric sensorimotor function with barostat (sensitivity, accommodation). We measured psychosocial factors (abuse history, alexithymia, trait anxiety, depression, panic disorder) and 'somatization' using self-report questionnaires, and presence of IBS and CF-like symptoms. Hierarchical multiple logistic regression was used to determine which of these factors were independently associated with co-morbid IBS and CF-like symptoms, including testing of potential mediator effects. KEY RESULTS: Co-morbid IBS or CF-like symptoms respectively were found in 142 (56.8%) and 102 (39.4%) patients; both co-morbidities were not significantly associated (P=0.27). Gastric accommodation (ß=0.003, P=0.04) and 'somatization' (ß=0.17, P= 0.0003) were independent risk factors for IBS (c=0.74, P<0.0001); the effect of adult abuse (ß=0.72, P=0.20) was mediated by 'somatization'. Depression (ß=0.16, P=0.008) and 'somatization' (ß=0.18, P=0.004) were overlapping risk factors for CF-like symptoms (c=0.83, P<0.0001); the effects of alexithymia and lifetime abuse were mediated by depression and 'somatization', respectively. CONCLUSIONS & INFERENCES: 'Somatization' is a common risk factor for co-morbid IBS and CF-like symptoms in FD and mediates the effect of abuse. Gastric sensorimotor function and depression are specific risk factors for co-morbid IBS and CF-like symptoms, respectively.

Risk factors for impaired health-related quality of life in functional dyspepsia.

BACKGROUND: The influence of patient characteristics on HRQoL in functional dyspepsia is poorly understood. AIM: To determine the contribution of gastric sensorimotor function, psychosocial factors & 'somatization' to HRQoL in functional dyspepsia. METHODS: In 259 tertiary care functional dyspepsia patients, we studied gastric sensorimotor function with barostat. We measured psychosocial factors and 'somatization' using self-report questionnaires. HRQoL was assessed using the SF-36 physical and mental composite scores (PCS, MCS). Bivariate associations between gastric sensorimotor function, psychosocial factors and 'somatization' on the one hand and PCS and MCS on the other were estimated. Variables significantly associated with PCS or MCS in bivariate analysis were entered into hierarchical multiple linear regression models. RESULTS: Mean PCS was 40.1 ± 9.5; mean MCS was 45.1 ± 10.8. 'Somatization' (P < 0.0001) and chronic fatigue (P = 0.002) were significantly associated with impaired PCS (R² = 0.52, P < 0.0001). The effects of abuse history and depression were 'mediated' by 'somatization'. Trait anxiety (P = 0.02), alexithymia (P = 0.06), depression (P = 0.06), positive affect (P < 0.0001), negative affect (P = 0.002) and generalised anxiety disorder (P = 0.01) were significantly associated with impaired MCS (R² = 0.67, P < 0.0001). CONCLUSIONS: 'Somatization' is the most important risk factor for impaired physical HRQoL in functional dyspepsia; it 'mediates' the effect of abuse history and depression. Mental HRQoL is mainly explained by psychosocial factors.

Reasons for dropout in infertility treatment.

BACKGROUND: The objective of this study was to explore the reasons why couples discontinue fertility treatment. METHODS: A retrospective exploratory study was performed at the Leuven University Fertility Centre, a university hospital-based fertility center. Women who discontinued treatment between September 2000 and December 2001 were contacted in 2004-2005 by telephone for a standardized interview which covered 9 dropout reasons. For each reason, its importance on the decision to stop treatment was measured on an 11-point Likert scale. RESULTS: On average, psychological burden (x = 5.96) had the highest impact on the decision to stop treatment followed by physical burden (x = 4.48) and female age (x = 3.64). Perceived lack of staff expertise (x = 1.84), negative impact on social contacts (x = 2.12) and financial burden (x = 2.16) had the lowest impact on the decision to stop treatment. Longer duration of infertility was significantly positively correlated with a higher rating of physical burden as a reason to discontinue treatment (r = 0.48; p < 0.05). DISCUSSION: On average, psychological burden appears to be most frequently named as the number one reason to discontinue infertility treatment, whereas financial burden had the lowest impact. Longer duration of infertility is associated with more externalizing reasons to discontinue treatment.

[Tolerance and efficacy of atovaquone-proguanil for the treatment of paediatric imported Plasmodium falciparum malaria in France: clinical practice in a university hospital in Paris]. / Tolérance et efficacité de l'atovaquone-proguanil dans le traitement du paludisme d'importation àPlasmodium falciparum de l'enfant en France métropolitaine: expérience d'un centre hospitalier parisien.

UNLABELLED: Only few drugs for uncomplicated Plasmodium falciparum malaria are available in children. Atovaquone-proguanil is a recent antimalarial drug licensed in France for the uncomplicated P. falciparum malaria in adults. Few paediatric studies have evaluated atovaquone-proguanil in children for uncomplicated malaria in endemic area, but no study have evaluated this treatment for imported malaria. OBJECTIVE: To evaluate treatment by atovaquone-proguanil for uncomplicated and imported P. falciparum malaria in children. METHODS: We retrospectively evaluated the tolerance and the efficacy of atovaquone-proguanil in the children admitted in Robert-Debré Hospital (Paris) for a P. falciparum malaria. From January 2004 to December 2005, 48 children with a median age of 7,5 years (IQR 4-11) were treated with atovaquone-proguanil for a uncomplicated P. falciparum malaria, except for 5 children who had an isolated hyperparasitemia greater or equal to 5%. RESULTS: Atovaquone-proguanil was stopped for 3/48 children because of vomiting. Fever resolved in all the children between Day 3 and 7, following the beginning of the treatment. One child, with a favourable outcome, had a positive parasitemia at Day 4 equal to the initial parasitemia (0,1%). No late therapeutic failure was observed among the 24 children evaluated up to one month after starting treatment. CONCLUSION: Atovaquone-proguanil is an efficient and well-tolerated antimalarial treatment for uncomplicated P. falciparum malaria in children. The risk of vomiting should lead to a systematic initial hospitalisation of children treated with atovaquone-proguanil.