Child appraisals of injustice in the context of acute and chronic pain: An interpretative phenomenological analysis.

BACKGROUND: Recent research has found child pain-related injustice appraisals to be associated with adverse pain-related outcomes. However, this evidence is mainly based on research using a measure developed for adults in the context of accident-related injuries, which may not translate to paediatric pain populations. Research on the phenomenology of child pain-related injustice appraisals is lacking. This study aimed to examine the phenomenology of pain-related injustice appraisals among both pain-free children and children living with chronic pain, to compare and contrast their experiences. METHODS: Two focus groups were held with pain-free children (n = 16), and three focus groups were held with paediatric chronic pain patients attending a rehabilitation centre (n = 15) in Belgium. Interpretative phenomenological analysis was applied. RESULTS: Two injustice-related themes were generated from the focus groups with pain-free children: (1) 'Someone else is at fault' and (2) 'I am in pain and he is not'. Two injustice-related themes were generated from the focus groups with paediatric chronic pain patients: (1) 'People don't see my pain' and (2) 'I am missing out because of my pain'. CONCLUSIONS: This study offers the first exploration of the phenomenology of child pain-related injustice appraisals in both pain-free children and paediatric pain patients. Findings highlight the interpersonal nature of lived injustice experiences caused by chronic pain, which is not fully captured by existing child pain-related injustice measures. Findings further suggest that pain-related injustice notions may not be extrapolated from a chronic to an acute pain context. SIGNIFICANCE: The current study offers the first exploration of the phenomenology of child pain-related injustice appraisals in both pain-free children and paediatric chronic pain patients. Findings highlight the interpersonal nature of injustice appraisals that are specific to the experience of chronic rather than acute pain. These appraisals are not fully captured by current child pain-related injustice measures.

Subtyping youngsters with obesity: A theory-based cluster analysis.

Psychological mechanisms play a crucial role in explaining weight gain. Aim of the present study was to identify subtypes in youngsters with obesity in line with these mechanisms. Defining homogeneous clusters within this heterogeneous group provides relevant information for personalized treatments. Data were collected in N = 572 participants (51% boys, aged 7-19) with extreme obesity (%BMI M = 187.8; SD = 30.9) recruited in an inpatient treatment centre. Based on psychological models of overweight/obesity, the Affect Regulation Model, the Reward Deficiency Model and The Dual Pathway Model, cluster variables were selected assessing emotional eating, reward reactivity and regulative capacities. Youngsters reported on emotional eating (DEBQ Emotional Eating) and reward sensitivity (BAS), while parents reported on children's regulative Executive Functions (BRIEF). Characteristics of the different clusters were examined concerning weight variables (pre and post treatment) and variables indexing problematic eating (DEBQ External Eating, Ch-EDE), affect regulation (FEEL-KJ) and depressive symptoms (CDI). Hierarchical cluster analyses supported the presence of three clusters, further evaluated by K-means cluster analyses. The cluster solutions differed according to age and sex (boys 7-13, boys 14-19, girls 7-13, girls 14-19). In all four age and gender subsamples, an "Emotional Eating" cluster displaying a vulnerable profile (high depression, maladaptive emotion regulation, problematic eating) and a "Reward Deficiency" cluster displaying a more resilient profile were detected. In girls 7-13, a "Weak Executive Functioning" indicative of insufficient self-regulative capacities, showed moderate to high emotional problems and problematic eating. In the other subgroups, the "Mean Level Functioning" cluster also showed elevated emotional problems and problematic eating. Given that different clusters can be identified, and given that these clusters have different profiles on emotional problems and problematic eating, subtyping youngsters with severe obesity is indicated, setting the stage for personalized treatments.

Inflammation in obese children and adolescents: Association with psychosocial stress variables and effects of a lifestyle intervention.

Obesity in childhood and adolescence is a complex health issue that has detrimental effects on the physical and psychological health of the youngster, both in the short and long term. A characteristic of obesity is the associated chronic low-grade inflammation which can result in insulin resistance. Previous research suggested that biomarkers referring to such increased inflammation may help in understanding resistance to weight loss. Whether and how psychosocial factors are related with inflammation remains to be proven. The current study consisted of 594 children and adolescents (7-19 years), of whom 480 had follow-up data, who enrolled for a ten-month inpatient multidisciplinary obesity treatment consisting of healthy food routines, physical activities and psychological treatment. The purpose of the study was to explore (1) the relationship between inflammation and psychosocial stress variables (i.e., depressive symptoms, eating behavior, concerns about eating/shape/weight, insecure parent-child attachment) (correlational and multiple regression analysis), (2) whether a lifestyle intervention for obese youngsters results in decreased C-reactive protein (CRP) values (paired t-test) and (3) which psychosocial variables influence this CRP change as indication of treatment success (multiple regression analysis with change in BMI as control variable). Results showed that the psychosocial stress variables emotional eating, external eating and attachment anxiety are related to higher CRP values. Our data further suggested that a lifestyle intervention decreases the CRP values. This significant reduction in blood inflammatory marker was besides being influenced by weight loss also dependent on psychosocial variables, more specific on self-reported attachment avoidance, as this latter was related to less CRP decrease.

Using confidence interval-based estimation of relevance to explore bottom-up and top-down determinants of problematic eating behavior in children and adolescents with obesity from a dual pathway perspective.

Prevalence of overweight and obesity in children and adolescents is high, not only in Western countries but also in developing countries. Efforts to improve prevention and treatment programs are needed. Given their essential role in weight problems, knowledge of determinants of problematic eating behavior ('External Eating' and 'Emotional Eating') is crucial for intervention development. Inspired by Appelhans' Dual Process Theory of Eating Behavior, the present study evaluated the importance of top-down regulative capacities and bottom-up reactivity, using the CIBER approach. CIBER is an innovative statistical approach to test the importance of behavior determinants, based on confidence intervals, instead of significance testing of point estimates. Survey data on different aspects of executive functioning (as indices of regulative capacities: Inhibition, Cognitive Flexibility, Emotional Control, Initiation, Working Memory, Planning/Organizing, Organization of materials, and Monitoring) and reward sensitivity (as an index of reactivity) were collected in a large sample of children and adolescents (n = 572) with severe obesity (adjBMI > 180%). Results showed that Emotional Eating is determined by Emotional Control, while External Eating is determined by Reward Sensitivity. The finding that differential mechanisms underlie different aspects of problematic eating suggests the need for using tailored intervention techniques to address altered reactivity and weak regulative capacities.

Economic evaluation of S. boulardii CNCM I-745 for prevention of antibioticassociated diarrhoea in hospitalized patients.

Interest in administration of probiotics to prevent antibiotic-associated diarrhoea (AAD) in hospitalized patients is increasing. We determined the cost of antibiotic-associated diarrhoea in hospital settings for non-complicated and Clostridium difficile (C.diff) complicated AAD, and performed a health-economic analysis of AAD prevention with S. boulardii CNCM I-745 (S. boulardii) from data collected in 1 university and 3 regional hospitals in Flanders. Using a decision tree analytic model, costs and effects of S. boulardii for AAD prevention are calculated. Incremental costs due to AAD, including increased length of hospitalization, were calculated using bottom-up and top-down costing approaches from a hospital, healthcare payer (HCP) and societal perspective. Model robustness was tested using sensitivity analyses. Additional costs per hospitalized patient range from € 277.4 (hospital) to € 2,150.3 (societal) for non-complicated and from € 588.8 (hospital) to € 2,239.1 (societal) for C. diff. complicated AAD. Using S. boulardii as AAD prevention results in cost savings between € 50.3 (bottom-up) and € 28.1 (topdown) per patient treated with antibiotics from the HCP perspective; and € 95.2 and € 14.7 per patient from the societal and hospital perspectives. Our analysis shows the potential for using S. boulardii as AAD prophylactic treatment in hospitalized patients. Based on 831,655 hospitalizations with antibiotic administration in 2014 and € 50.3 cost saving per patient on antibiotics, generalized use of S. boulardii could result in total annual savings up to € 41.8 million for the Belgian HCP.

Post-treatment phone contact: a weight maintenance strategy in obese youngsters.

This study investigated the effect of post-treatment phone contact on weight-loss maintenance and activity behaviour in obese youngsters. In all, 20 patients who completed a weight reduction program were randomly assigned to a 5-month maintenance programme (experimental) or control condition. Following the maintenance programme, patients sent a weekly activity diary to the therapist, who in turn phoned them biweekly to discuss their activities. Body weight, stature and physical activity were measured before and after the maintenance programme. The control group showed a continuous increase in overweight after initial treatment, while the experimental group showed a steep increase during the summer holidays (no intervention), but this increase slowed down during the maintenance programme (P<0.05). Moderate-to-high intensity activities increased during the maintenance programme in the experimental group, but decreased in the control group (P<0.001). In conclusion, post-treatment phone contact appears to have the potential to be an effective maintenance strategy in obese youngsters.

Mapping of murine Th1 helper T-Cell epitopes of mycolyl transferases Ag85A, Ag85B, and Ag85C from Mycobacterium tuberculosis.

BALB/c (H-2(d)) and C57BL/6 (H-2(b)) mice were infected intravenously with Mycobacterium tuberculosis H37Rv or vaccinated intramuscularly with plasmid DNA encoding each of the three mycolyl transferases Ag85A, Ag85B, and Ag85C from M. tuberculosis. Th1-type spleen cell cytokine secretion of interleukin-2 (IL-2) and gamma interferon (IFN-gamma) was analyzed in response to purified Ag85 components and synthetic overlapping peptides covering the three mature sequences. Tuberculosis-infected C57BL/6 mice reacted strongly to some peptides from Ag85A and Ag85B but not from Ag85C, whereas tuberculosis-infected BALB/c mice reacted only to peptides from Ag85A. In contrast, spleen cells from both mouse strains produced elevated levels of IL-2 and IFN-gamma following vaccination with Ag85A, Ag85B, and Ag85C DNA in response to peptides of the three Ag85 proteins, and the epitope repertoire was broader than in infected mice. Despite pronounced sequence homology, a number of immunodominant regions contained component specific epitopes. Thus, BALB/c mice vaccinated with all three Ag85 genes reacted against the same amino acid region, 101 to 120, that was also immunodominant for Ag85A in M. bovis BCG-vaccinated and tuberculosis-infected H-2(d) haplotype mice, but responses were completely component specific. In C57BL/6 mice, a cross-reactive T-cell response was detected against two carboxy-terminal peptides spanning amino acids 241 to 260 and 261 to 280 of Ag85A and Ag85B. These regions were not recognized at all in C57BL/6 mice vaccinated with Ag85C DNA. Our results underline the need for comparative analysis of all three Ag85 components in future vaccination studies.

Improved tuberculosis DNA vaccines by formulation in cationic lipids.

Mice were vaccinated with plasmid DNA (pDNA) encoding antigen 85A (Ag85A), Ag85B, or PstS-3 from Mycobacterium tuberculosis either in saline or formulated for intramuscular injections in VC1052:DPyPE (aminopropyl-dimethyl-myristoleyloxy-propanaminium bromide-diphytanoylphosphatidyl-ethanolamine) (Vaxfectin; Vical, Inc., San Diego, Calif.) or for intranasal instillations in GAP-DLRIE:DOPE (aminopropyl-dimethyl-bis-dodecyloxy-propanaminium bromide-dioleoylphosphatidyl-ethanolamine). These two novel cationic and neutral colipid formulations were previously reported to be effective adjuvants for pDNA-induced antibody responses. The levels of Ag85-specific total immunoglobulin G (IgG) and IgG isotypes were all increased 3- to 10-fold by formulation of pDNA in Vaxfectin. The level of production of splenic T-cell-derived Th1-type cytokines (interleukin-2 and gamma interferon) in response to purified Ag85 and to synthetic peptides spanning the entire Ag85A protein was also significantly higher in animals vaccinated with pDNA formulated in Vaxfectin. Cytolytic T-lymphocyte responses generated by pDNA encoding phosphate-binding protein PstS-3 in Vaxfectin were better sustained over time than were those generated by PstS-3 DNA in saline. Intranasal immunization with Ag85A DNA in saline was completely ineffective, whereas administration in GAP-DLRIE:DOPE induced a positive Th1-type cytokine response; however, the extent of the latter response was clearly lower than that obtained following intramuscular immunization with the same DNA dose. Combined intramuscular and intranasal administrations in cationic lipids resulted in stronger immune responses in the spleen and, more importantly, in the lungs as well. Finally, formulation in Vaxfectin increased the protective efficacy of the Ag85B DNA vaccine, as measured by reduced relative light unit counts and CFU counts in the spleen and lungs from mice challenged with bioluminescent M. tuberculosis H37Rv. These results may be of importance for future clinical use of DNA vaccines in humans.

Protective efficacy of a DNA vaccine encoding antigen 85A from Mycobacterium bovis BCG against Buruli ulcer.

Buruli ulcer, caused by Mycobacterium ulcerans, is characterized by deep and necrotizing skin lesions, mostly on the arms and legs. Together with tuberculosis and leprosy, this mycobacterial disease has become a major health problem in tropical and subtropical regions, particularly in central and western Africa. No specific vaccine is available for Buruli ulcer. There is, however, evidence in the literature that suggests a cross-reactive protective role of the tuberculosis vaccine M. bovis BCG. To identify potential mechanisms for this cross-protection, we identified and characterized the M. ulcerans homologue of the important protective mycobacterial antigen 85 (Ag85A) from BCG. The homologue is well conserved in M. ulcerans, showing 84.1% amino acid sequence identity and 91% conserved residues compared to the sequence from BCG. This antigen was sufficiently conserved to allow cross-reactive protection, as demonstrated by the ability of M. ulcerans- infected mice to exhibit strong cellular immune responses to both BCG and its purified Ag85 complex. To further address the mechanism of cross-reactive protection, we demonstrate here that prior vaccination with either BCG or plasmid DNA encoding BCG Ag85A is capable of significantly reducing the bacterial load in the footpads of M. ulcerans- infected mice, as determined by Ziehl-Neelsen staining and by actual counting of CFU on 7H11 Middlebrook agar. Together, the results reported here support the potential of a cross-protective Ag85-based future vaccine against tuberculosis, Buruli ulcer, and leprosy.

Improved immunogenicity and protective efficacy of a tuberculosis DNA vaccine encoding Ag85 by protein boosting.

C57BL/6 mice were vaccinated with plasmid DNA encoding Ag85 from Mycobacterium tuberculosis, with Ag85 protein in adjuvant, or with a combined DNA prime-protein boost regimen. While DNA immunization, as previously described, induced robust Th1-type cytokine responses, protein-in-adjuvant vaccination elicited very poor cytokine responses, which were 10-fold lower than those observed with DNA immunization alone. Injection of Ag85 DNA-primed mice with 30 to 100 microg of purified Ag85 protein in adjuvant increased the interleukin-2 and gamma interferon (IFN-gamma) response in spleen two- to fourfold. Further, intracellular cytokine analysis by flow cytometry also showed an increase in IFN-gamma-producing CD4(+) T cells in DNA-primed-protein-boosted animals, compared to those that received only the DNA vaccination. Moreover, these responses appeared to be better sustained over time. Antibodies were readily produced by all three methods of immunization but were exclusively of the immunoglobulin G1 (IgG1) isotype following protein immunization in adjuvant and preferentially of the IgG2a isotype following DNA and DNA prime-protein boost vaccination. Finally, protein boosting increased the protective efficacy of the DNA vaccine against an intravenous M. tuberculosis H37Rv challenge infection, as measured by CFU or relative light unit counts in lungs 1 and 2 months after infection. The capacity of exogenously given protein to boost the DNA-primed vaccination effect underlines the dominant role of Th1-type CD4(+) helper T cells in mediating protection.

Tuberculosis DNA vaccine encoding Ag85A is immunogenic and protective when administered by intramuscular needle injection but not by epidermal gene gun bombardment.

Immunogenicity and protective efficacy of a DNA vaccine encoding Ag85A from Mycobacterium tuberculosis were compared in BALB/c and C57BL (B6 and B10) mice immunized by intramuscular (i.m.) needle injection or epidermal gene gun (gg) bombardment. In BALB/c mice, gg immunization could induce elevated antibody and cytotoxic T lymphocyte responses with plasmid doses 50-fold lower than those required for i.m. immunization. Interleukin-2 (IL-2) and gamma interferon (IFN-gamma) secretion, however, was much lower in gg-immunized than in i.m.-immunized BALB/c mice. On the other hand, C57BL mice reacted only very weakly to gg immunization, whereas elevated Ag85A-specific antibody, IL-2, and IFN-gamma responses (significantly higher than in BALB/c mice) were detected following vaccination by the i.m. route. Antibody isotypes were indicative of Th2 activation following gg injection of BALB/c and of Th1 activation following i.m. injection of C57BL mice. Finally, C57BL but not BALB/c mice were protected by i.m. Ag85A DNA immunization against intravenous M. tuberculosis challenge, as measured by reduced numbers of CFU in spleen and lungs, compared to animals vaccinated with control DNA. Gene gun immunization was not effective in either BALB/c or C57BL mice. These results indicate that i.m. DNA vaccination is the method of choice for the induction of protective Th1 type immune responses with the Ag85A tuberculosis DNA vaccine.

Characterization of a new set of mutants deficient in fermentation-induced loss of stress resistance for use in frozen dough applications.

In frozen dough applications a prefermentation period during the preparation of the dough is unavoidable and might also be important to obtain bread with a good texture. A major disadvantage of the prefermentation period is that it is associated with a rapid loss of the freeze resistance of the yeast cells. A major goal for the development of new baker's yeast strains for use in frozen dough applications is the availability of strains that maintain a better freeze resistance during the prefermentation period. We have isolated mutants that retain a better stress resistance during the initiation of fermentation. Some of these showed the same growth rate and fermentation capacity as the wild type cells. These mutants are called 'fil', for deficient infermentation induced loss of stress resistance. First we used laboratory strains and heat stress treatment, given shortly after the initiation of fermentation, as the selection protocol. The first two mutants isolated in this way were affected in the glucose-activation mechanism of the Ras-cAMP pathway. The fil1 mutant had a partially inactivating point mutation in CYR1, the gene encoding adenylate cyclase, while fil2 contained a nonsense mutation in GPR1. GPR1 encodes a member of the G-protein coupled receptor family which acts as a putative glucose receptor for activation of the Ras-cAMP pathway. In a next step we isolated fil mutants directly in industrial strains using repetitive freeze treatment of doughs as selection protocol. Surviving yeast strains were tested individually for maintenance of fermentation capacity after freeze treatment in laboratory conditions and also for the best performing strains in frozen doughs prepared with yeast cultivated on a pilot scale. The most promising mutant, AT25, displayed under all conditions a better maintenance of gassing power during freeze-storage. It was not affected in other commercially important properties and will now be characterised extensively at the biochemical and molecular level.

Identification of genes responsible for improved cryoresistance in fermenting yeast cells.

Using repetitive freezing and thawing, different mutant industrial Saccharomyces cerevisiae strains with increased freeze resistance have been isolated. To get a better insight in the mechanisms responsible for this elevated resistance and to give us the opportunity to modify other strains so that they become more suitable for use in frozen dough preparations, we applied the microarray technology in order to identify genes that are differentially expressed in a freeze-resistant mutant when compared to a freeze-sensitive industrial yeast strain.

Lack of protection in mice and necrotizing bronchointerstitial pneumonia with bronchiolitis in guinea pigs immunized with vaccines directed against the hsp60 molecule of Mycobacterium tuberculosis.

In this study, the hsp60 and hsp70 heat shock protein antigens of Mycobacterium tuberculosis were tested as potential vaccine candidates, using purified recombinant protein antigens or antigens encoded in the form of a DNA plasmid vaccine. Guinea pigs vaccinated with a mixture of the two proteins showed no evidence of resistance to low-dose aerosol challenge infection and quickly developed severe lung damage characterized by necrotizing bronchointerstitial pneumonia and bronchiolitis. As a result, we turned instead to a DNA vaccination approach using a plasmid encoding the hsp60 antigen of M. tuberculosis. Although immunogenic in mice, vaccination with plasmid DNA encoding hsp60 was not protective in that model or in the guinea pig model and again gave rise to similar severe lung damage. This study seriously questions the safety of vaccines against tuberculosis that target highly conserved heat shock proteins.

Cloning of the gene encoding a 22-kilodalton cell surface antigen of Mycobacterium bovis BCG and analysis of its potential for DNA vaccination against tuberculosis.

Using spleen cells from mice vaccinated with live Mycobacterium bovis BCG, we previously generated three monoclonal antibodies reactive against a 22-kDa protein present in mycobacterial culture filtrate (CF) (K. Huygen et al., Infect. Immun. 61:2687-2693, 1993). These monoclonal antibodies were used to screen an M. bovis BCG genomic library made in phage lambdagt11. The gene encoding a 233-amino-acid (aa) protein, including a putative 26-aa signal sequence, was isolated, and sequence analysis indicated that the protein was 98% identical with the M. tuberculosis Lppx protein and that it contained a sequence 94% identical with the M. leprae 38-mer polypeptide 13B3 recognized by T cells from killed M. leprae-immunized subjects. Flow cytometry and cell fractionation demonstrated that the 22-kDa CF protein is also highly expressed in the bacterial cell wall and membrane compartment but not in the cytosol. C57BL/6, C3H, and BALB/c mice were vaccinated with plasmid DNA encoding the 22-kDa protein and analyzed for immune response and protection against intravenous M. tuberculosis challenge. Whereas DNA vaccination induced elevated antibody responses in C57BL/6 and particularly in C3H mice, Th1-type cytokine response, as measured by interleukin-2 and gamma interferon secretion, was only modest, and no protection against intravenous M. tuberculosis challenge was observed in any of the three mouse strains tested. Therefore, the 22-kDa antigen seems to have little potential for a DNA vaccine against tuberculosis, but it may be a good candidate for a mycobacterial antigen detection test.

Immunogenicity and protective efficacy of tuberculosis DNA vaccines encoding putative phosphate transport receptors.

Using culture filtrate Ag-specific mAbs generated from mycobacteria-infected H-2b haplotype mice, we have previously identified three genes in the Mycobacterium tuberculosis genome, encoding proteins homologous to the periplasmic ATP-binding cassette phosphate-binding receptor PstS of the phosphate-specific transport system of E. coli. To define the potential vaccinal properties of these phosphate-binding proteins, female C57BL/6 mice were injected i.m. with plasmid DNA encoding PstS-1, PstS-2, or PstS-3 proteins from M. tuberculosis and immunogenicity and protective efficacy against i.v. challenge with M. tuberculosis H37Rv was analyzed. Significant levels of highly Ag-specific Abs and Th1-type cytokines IL-2 and IFN-gamma could be detected following vaccination with each of the three genes. However, only mice vaccinated with PstS-3 DNA demonstrated significant and sustained reduction in bacterial CFU numbers in spleen and lungs for 3 mo after M. tuberculosis challenge, as compared with CFU counts in mice vaccinated with control DNA. Vaccination with PstS-2 DNA induced a modest reduction in CFU counts in spleen only, whereas vaccination with PstS-1 DNA was completely ineffective in reducing bacterial multiplication. In conclusion, our results indicate that DNA vaccination is a powerful and easy method for comparative screening of potentially protective Ags from M. tuberculosis and that the PstS-3 protein is a promising new subunit vaccine candidate.

Vaccination with plasmid DNA encoding mycobacterial antigen 85A stimulates a CD4+ and CD8+ T-cell epitopic repertoire broader than that stimulated by Mycobacterium tuberculosis H37Rv infection.

Vaccination of mice with plasmid DNA carrying the gene for the major secreted mycobacterial antigen 85A (Ag85A) from Mycobacterium tuberculosis is a powerful technique for generating robust specific Thl helper T-cell responses, CD8+-mediated cytotoxicity, and protection against M. tuberculosis challenge (K. Huygen et al., Nat. Med. 2:893-898, 1996). We have now analyzed in more detail the antigen-specific immune CD4+- and CD8+-T-cell responses induced in BALB/c mice vaccinated with Ag85A DNA and have compared these responses to those generated by intravenous infection with M. tuberculosis. T-cell-epitope mapping, as measured by interleukin-2 and gamma interferon secretion from splenic T cells restimulated in vitro with synthetic 20-mer peptides spanning the complete mature sequence of Ag85A, demonstrated that DNA vaccination stimulated a stronger and broader T-cell response than did M. tuberculosis infection. Moreover, elevated cytotoxic T lymphocyte (CTL) activity against Ag85A-transfected and peptide-pulsed P815 target cells could be generated exclusively by vaccination with plasmid DNA, not following M. tuberculosis infection. By using DNA vaccination, three Ag85A CTL epitopes with predicted major histocompatibility complex class I binding motifs were defined. One of them was previously reported as a dominant, promiscuously recognized T-cell epitope in healthy humans with primary infections. These data strengthen the potential of DNA vaccination with respect to inducing antituberculous immunity in humans.

Double-blind randomized controlled study of the efficacy and tolerability of two reversible monoamine oxidase A inhibitors, pirlindole and moclobemide, in the treatment of depression.

The aim of this double-blind randomized study was to compare the efficacy and the tolerability of moclobemide (300-600 mg daily) and pirlindole (150-300 mg daily), two reversible inhibitors of MAO-A (RIMAs), in the treatment of depression. In total 116 patients were included in the trial, 111 patients (52 patients on pirlindole and 59 patients on moclobemide) were evaluable for efficacy and safety, and 77 patients completed the whole study (42 days of administration). Both treatments produced highly significant improvements in the Hamilton Depression Rating Scale (HDRS) score, the Hamilton Anxiety Rating Scale (HARS) score and the Montgomery-Asberg Rating Scale (MADRS) score from day 7 to day 42. The pattern of development of the three scores in the two groups did not differ significantly. After 42 days of treatment, an improvement of > or = 50% in the HDRS score was noted in 80% and 67% of patients in the pirlindole and moclobemide groups, respectively. A total of 30 (58%) patients on pirlindole and 33 (56%) patients on moclobemide experienced side-effects that were considered to be possibly or probably related to the medication. The differences between the two drugs were non-significant for all types of side-effect, with the exception of dry mouth and tachycardia, which were significantly more frequent with moclobemide.

A chromosome 18 genetic linkage study in three large Belgian pedigrees with bipolar disorder.

The contribution of genetic factors to the susceptibility for affective disorders has been firmly established. Recent reports found evidence for a susceptibility locus for affective disorders in 2 regions on chromosome 18. We describe 3 large Belgian pedigrees with multiple patients with affective disorders. Both chromosome 18 regions were investigated in the 3 families, using parametric and nonparametric segregation methods. In the pericentromeric region, all evidence was against a disease gene in our families. Also the data obtained for the distal part of 18q, argue against a genetic susceptibility factor in our sample.

Case study of quality assurance in the administration of chemotherapy.

The purpose of the study was to monitor the quality of chemotherapy administration within the department of oncology, of the university hospitals in Leuven (Belgium), by focusing on prescription and documented administration of chemotherapy. First, the actors and phases of the process were identified. Then selected patient records of three different types of chemotherapy were retrospectively analysed for 453 chemotherapy administrations. Study results indicated an important need to standardize the nursing and medical guidelines concerning chemotherapy administration. A formal task force was established to work on a multidisciplinary basis. The goals were to improve the routine process by identifying practical problems at any level and to standardize procedures by replacing all poorly defined "habits" by well-structured guidelines.