Working memory training in children with neurodevelopmental disorders and intellectual disabilities, the role of coaching: A double-blind randomised controlled trial.

BACKGROUND: Working memory training (WMT) can offer therapeutic benefits to patients with neurodevelopmental disorders (NDD) and mild to borderline intellectual disability (MBID). However, consistent evidence for treatment benefits of WMT over placebo training is missing. So far, participants in double-blind research designs did receive non-specific coaching, whereas active coaching based on individual training results might increase the efficacy of WMT. Furthermore, the intensity and duration of WMT is often too stressful for these children. This study therefore investigated whether a less intensive but more prolonged WMT, with active personalised coaching and feedback, would reduce behavioural symptoms and improve neurocognitive functioning and academic achievements in children with NDD and MBID. METHOD: A double-blind randomised controlled trial in children (aged 10;0-13;11) with MBID (60 < IQ < 85) and ADHD and/or ASD evaluated the effects of a less intensive but prolonged version of the original Cogmed WMT (30 min a day, 4 days a week, 8 weeks in total). Eighteen participants received active, personalised coaching and feedback, based on their actual individual performance during training. Twenty-two received general non-personalised coaching for the same amount of time. Executive functioning, academic achievements and several behavioural measurements were administered, before and after training, with a 6-months follow-up. RESULTS: We observed a significant effect of time on both primary and secondary outcome measures, indicating that all children improved in working memory performance and other neurocognitive and academic outcomes. The interaction between time and group was not significant. DISCUSSION: This study was unable to document superior effects of active personalised coaching and feedback compared with general non-personalised coaching and no feedback in an adaptive WMT in children with MBID and NDD. The objectively documented changes over time suggest that for these vulnerable children, a regular, structured and structural contact with a coach and adapted exercises is enough to develop therapy fidelity, boost motivation and improve neurodevelopmental task performance. Further research is needed to examine which possible subgroups within this heterogenic group of children profit more from WMT compared with other subgroups.

How do group workers respond to suicidal behavior? Experiences and perceptions of suicidal female adolescents residing in secure residential youth care in the Netherlands.

BACKGROUND: Adolescent suicidal behavior, including non-suicidal self-injury, is increasingly prevalent in Secure Residential Youth Care (SRYC) in the Netherlands. Group workers play a vital role in the well-being and functioning of adolescents in SRYC as they interact with adolescents on a daily basis. However, we have little understanding of how adolescents perceive group workers' responses to suicidal behavior and we lack knowledge about the impact of these responses on adolescents and the group climate. AIM: The aim of this study is to explore (a) how adolescents value group workers responses towards suicidal behavior and (b) the impact of these responses on adolescents, as well as (c) on the group climate. The results can be used to develop care-policy to improve care for suicidal adolescents in SYRC. METHOD: Eleven suicidal female adolescents residing in SRYC were interviewed. All adolescents had previously displayed suicidal behavior, including non-suicidal self-injury. Interviews were analyzed using grounded theory. CONCLUSION: This study presents the perceptions of suicidal female adolescents residing in SRYC about group workers' responses on suicidal behavior. Adolescents prefer group workers who react responsive to suicidal behavior. Responsive care, trust and connectedness help adolescents disclose their suicidal thoughts. Participants criticize group workers who are non-responsive as being distant, and their relationship with these group workers lacked trust, communication, a sense of connection, or personal depth. All adolescents underline the devastating impact of involuntary seclusion, and stress the importance of being able to disclose without fear of coercive consequences. Findings indicate that non-responsive reactions contribute to an increase in suicidal distress as well as a closed group climate.

[Learning from parents: qualitative study into an integrated family approach for parent and child]. / Leren van ouders: kwalitatief onderzoek naar geïntegreerde ggz voor ouder én kind.

BACKGROUND: The risk of transmission of psychopathology from parent to child is high. Psychological disorders of parents have an influence on parenting and on the development of the young child. An integrated treatment for parent and child, in which professionals from adult and infant mental health teams work together, is still not commonplace. AIM: To explore how parents have experienced the integrated family approach in mental health care foundation Dimence Groep and what they believe to be barriers and facilitators. The results can be used to fine-tune the integrated family approach in mental health care. METHOD: Semi-structured interviews with 18 parents of young children (0-6 years). Interviews were analyzed using the thematic analysis approach. RESULTS: Perceived positive therapeutic results according to parents were described in the areas of the parent-child interaction, the parent’s mentalizing capacity, parenting skills, and confidence in the parental role. Within the main themes of barriers and facilitators, several subthemes were clustered such as the consideration of the entire (family)context, offering tailoring and flexibility, cooperation between the departments, shared decision-making and the importance of the therapeutic relationship. CONCLUSION: According to parents who suffer from psychological disorders who have young children, an integrated family approach, in which the adult and infant mental health teams work together, is of added value. The findings from this qualitative research can be used to develop a broader transferable model for mental health care in the Netherlands.

Neurocognitive functioning of children with mild to borderline intellectual disabilities and psychiatric disorders: profile characteristics and predictors of behavioural problems.

BACKGROUND: The aim of the current study was twofold: first, to uncover a neurocognitive profile of normative and relative strengths and weaknesses that characterises an extremely vulnerable group of children with mild to borderline intellectual disabilities (MBID) and co-morbid psychiatric disorders, and second, to investigate the relevance of these neurocognitive functions explaining internalising and externalising symptoms. METHOD: We recruited 45 children (Mage  = 9.5, SDage  = 1.7; range 6-13 years) with MBID (Full-Scale IQ 50-85) and at least one psychiatric disorder. Neurocognitive functioning was examined utilising the Wechsler Intelligence Scale for Children - Fifth Edition (WISC-V) indices and the Cognitive Task Application (COTAPP), a comprehensive computerised self-paced task designed in such a manner that 'g' (an overall tendency of children with MBID to execute tasks with a slower reaction time and a higher error rate) has been corrected for in the administration of the task (i.e. completely self-paced) and in the operationalisation of outcome measures. Behavioural problems were measured using the CBCL and TRF. One-sample t-tests and binomial tests were carried out to compare performance with normative data. Regression analyses were used to examine the relationship between neurocognitive parameters and mental health. RESULTS: Compared with normative data, very small to very large effect sizes were found, indicating clear heterogeneity amongst neurocognitive domains relevant for children with MBID. Two prominent neurocognitive weaknesses emerged: processing speed - characterised by slowness and unstableness combined with a high drift rate and delayed processing of the previous trial, particularly under higher cognitive demands - and working memory - in terms of a weaker central executive and 'slave' systems to temporarily store information. Both domains were not clearly predictive of internalising or externalising problems. CONCLUSION: Children with MBID and psychiatric disorders are hampered by a strongly diminished processing speed and working memory capacity, together resulting in an overall limited processing capacity that may underlie the general developmental delays on domains that depend on fast and parallel processing of information (i.e. language, reading, mathematics and more complex forms of social cognition). Neurocognitive vulnerabilities are neither necessary nor sufficient to explain internalising and externalising problems; rather, a mismatch between the support needs and adaptations these children need, arising from their diminished processing capacity, and the inadequacy of the environment to compensate for this vulnerability may be of relevance.

Working memory training in children with borderline intellectual functioning and neuropsychiatric disorders: a triple-blind randomised controlled trial.

BACKGROUND: Poor working memory, lower IQ and maladaptive behaviour form a triple disability known to have negative effects on the academic and social development of children with borderline intellectual functioning (BIF; IQ: 70 < IQ < 85) and neuropsychiatric disorders [attention-deficit hyperactivity disorder (ADHD) and/or autism spectrum disorder (ASD)]. Treatment possibilities for these children are scarce and hardly evidence based. This study primarily investigated whether adaptive computerised working memory training (WMT) may lead to significantly more improvement on a non-trained visuospatial WM task compared with a non-adaptive control WMT (placebo) in children with BIF and neuropsychiatric disorders. As secondary outcome measures, we used the scores on several non-trained neuropsychological near-transfer and far-transfer tasks as well as behavioural measures. METHOD: We conducted a triple-blind placebo-controlled randomised clinical trial in 72 children (aged 10;0-13;11 years, 53 boys, 19 girls) with BIF and comorbid neuropsychiatric disorders (ADHD = 37, ASD = 21, both = 14) that were referred to child and adolescent psychiatry care, between May 2012 and March 2019. Children completed the Dutch version of Cogmed WMT, either the adaptive training version or the non-adaptive placebo version, 25 sessions (30-45 min a day), for 5 weeks. The primary outcome measure was the score on a non-trained visuospatial working memory task. The primary outcome was measured before and directly after 5 weeks of WMT and again 6 months after training. RESULTS: A total of 375 children were screened for eligibility and 72 were randomised. No significantly higher levels of improvement over time were found on our primary outcome measure in the experimental WMT group compared with the placebo control WMT, nor in the secondary (near-transfer and far-transfer tasks) or tertiary (behavioural measures) outcome measures. However, this study did show changes over time for these measurements for both the experimental and placebo conditions. CONCLUSIONS: This study was unable to document superior training effects over time of an adaptive WMT in children with BIF and neuropsychiatric disorders, compared with a placebo (non-adaptive) WMT. The objectively documented changes over time in the non-adaptive WMT arm suggest that these children with persistent impairments in WM may benefit from a structured learning environment that is associated with improvement of neurocognitive functioning and coping strategies. Further research is needed to examine which elements of cognitive training may be useful for which specific patients and to study long-term effects of training.

[Towards personalized child and adolescent psychiatry care by using routinely registered data from everyday clinical practice]. / Naar een gepersonaliseerde kinder- en jeugdpsychiatrie met registratiegegevens uit de dagelijkse zorgpraktijk.

BACKGROUND: Studying differences in the course and treatment effects of psychiatric disorders between subgroups of patients can provide suggestions to improve everyday clinical practice.
AIM: To illustrate how routinely registered data from child and adolescent psychiatry can be used to gain insight into differences in the development of patient groups.
METHOD: Multilevel analyses in four subgroups of youths with an autism spectrum disorder (asd; n = 1681; boys/girls, with/without comorbid psychiatric disorder) to investigate differences in the development of quality of life during the first six months of treatment.
RESULTS: Subgroups of youths with asd showed differences in development of quality of life, which can provide suggestions to establish personalized care.
CONCLUSION: Multicenter research in large samples is needed to investigate the robustness of our findings. The 'Research Data Infrastructure', containing routine outcome monitoring and electronic medical record data from more than 117.000 youths in child and adolescent psychiatry, offers a unique opportunity to perform large scale practice based research.

Longitudinal study of religiosity and mental health of adolescents with psychiatric problems. The TRAILS study.

PURPOSE: This study used longitudinal data to examine the influence of the religiosity of pre-adolescents with psychiatric problems on the course of mental health during adolescence. METHODS: In the TRAILS clinical cohort of 543 pre-adolescents (10-12 years), mental health problems were assessed using self-report at baseline, T2 (12-14 years), T3 (14-17 years), and T4 (17-21 years). The Youth Self Report (YSR) was used at baseline, T2, and T3, and the Adult Self Report (ASR) was used at T4. Religiosity was assessed at baseline using self-report and information from mothers and fathers, resulting in three categorical religiosity variables and six SOCON (Social Cultural Developments Questionnaire) religiosity scales that assess religiosity in greater detail. Repeated measure ANOVA analyses were performed for each independent religiosity variable with internalizing and externalizing problem behavior as dependent variables, gender as a factor and time (T1, T2, T3 and T4) as within factor. Results were adjusted for marital status of parents and socioeconomic status and corrected for multiple testing. RESULTS: There were main effects of the self-report SOCON scale "Humanistic beliefs" and gender and gender "by Humanistic beliefs" interaction effect on internalizing problems. Follow-up tests revealed that among females "high" scores on "Humanistic beliefs" were associated with increased internalizing problems. CONCLUSIONS: There were hardly any associations between religiosity and mental health in a clinical cohort of pre-adolescents up to adolescence. The exception being that among females strong humanistic beliefs were associated with internalizing problems. Implications of these findings are discussed.

The Effect of Pivotal Response Treatment in Children with Autism Spectrum Disorders: A Non-randomized Study with a Blinded Outcome Measure.

Purpose of this quasi-experimental trial was to investigate the effect of Pivotal response treatment (PRT) versus treatment as usual (TAU) on autism symptoms. Children with autism spectrum disorder (ASD), aged 3-8 years, received either PRT (n = 11) or TAU (n = 13). Primary outcome measure was the total score on the Autism Diagnostic Observation Schedule at pre- and posttreatment. Additionally, general problem behavior and parental stress levels were measured. Children in the PRT condition improved on the primary outcome measure compared to the TAU group with a small effect size [partial η2 = 0.22 (95 % CI 0.00-0.46)]. Neither group demonstrated significant changes in the secondary outcomes. This study suggests that PRT may improve autism symptoms in children with ASD over TAU.

Discovery of new methylation markers to improve screening for cervical intraepithelial neoplasia grade 2/3.

BACKGROUND: Assessment of DNA promoter methylation markers in cervical scrapings for the detection of cervical intraepithelial neoplasia (CIN) and cervical cancer is feasible, but finding methylation markers with both high sensitivity as well as high specificity remains a challenge. In this study, we aimed to identify new methylation markers for the detection of high-grade CIN (CIN2/3 or worse, CIN2+) by using innovative genome-wide methylation analysis (MethylCap-seq). We focused on diagnostic performance of methylation markers with high sensitivity and high specificity considering any methylation level as positive. RESULTS: MethylCap-seq of normal cervices and CIN2/3 revealed 176 differentially methylated regions (DMRs) comprising 164 genes. After verification and validation of the 15 best discriminating genes with methylation-specific PCR (MSP), 9 genes showed significant differential methylation in an independent cohort of normal cervices versus CIN2/3 lesions (p < 0.05). For further diagnostic evaluation, these 9 markers were tested with quantitative MSP (QMSP) in cervical scrapings from 2 cohorts: (1) cervical carcinoma versus healthy controls and (2) patients referred from population-based screening with an abnormal Pap smear in whom also HPV status was determined. Methylation levels of 8/9 genes were significantly higher in carcinoma compared to normal scrapings. For all 8 genes, methylation levels increased with the severity of the underlying histological lesion in scrapings from patients referred with an abnormal Pap smear. In addition, the diagnostic performance was investigated, using these 8 new genes and 4 genes (previously identified by our group: C13ORF18, JAM3, EPB41L3, and TERT). In a triage setting (after a positive Pap smear), sensitivity for CIN2+ of the best combination of genes (C13ORF18/JAM3/ANKRD18CP) (74 %) was comparable to hrHPV testing (79 %), while specificity was significantly higher (76 % versus 42 %, p ≤ 0.05). In addition, in hrHPV-positive scrapings, sensitivity and specificity for CIN2+ of this best-performing combination was comparable to the population referred with abnormal Pap smear. CONCLUSIONS: We identified new CIN2/3-specific methylation markers using genome-wide DNA methylation analysis. The diagnostic performance of our new methylation panel shows higher specificity, which should result in prevention of unnecessary colposcopies for women referred with abnormal cytology. In addition, these newly found markers might be applied as a triage test in hrHPV-positive women from population-based screening. The next step before implementation in primary screening programs will be validation in population-based cohorts.

Religiosity and mental health of pre-adolescents with psychiatric problems and their parents: the TRAILS study.

BACKGROUND: This study investigated the association between the religiosity of parents and pre-adolescents, and pre-adolescents' psychiatric problems. METHOD: In a clinic-referred cohort of 543 pre-adolescents at least once referred to a mental health outpatient clinic mental health problems were assessed using self-reports (Youth Self-Report; YSR), parent reports (Child Behavior Checklist; CBCL), and teacher reports (Teacher's Report Form; TRF) of child behavioral and emotional problems. Paternal, maternal, and pre-adolescent religiosity were assessed by self-report. MANCOVAs were performed for internalizing and externalizing problems as dependent variables, with maternal religiosity, paternal religiosity, pre-adolescent religiosity, parental religious harmony, and gender as independent variables, and socioeconomic status and divorce as covariates. RESULTS: Internalizing problems. Pre-adolescents of actively religious mothers had more internalizing symptoms than pre-adolescents of nonreligious mothers. Harmony and gender did not significantly affect the association between maternal religiosity and internalizing problems. Externalizing problems. No associations between religiosity of pre-adolescents, religiosity of mothers, religiosity of fathers and/or harmony of parents and externalizing problem behavior have been found. DISCUSSION AND CONCLUSIONS: Overall, associations between mental health and religiosity were modest to absent. Results are discussed in the context of a clinic-referred cohort, the quest phase of internalizing religious beliefs and role modeling of parents.

A four-gene methylation marker panel as triage test in high-risk human papillomavirus positive patients.

Cervical neoplasia-specific biomarkers, e.g. DNA methylation markers, with high sensitivity and specificity are urgently needed to improve current population-based screening on (pre)malignant cervical neoplasia. We aimed to identify new cervical neoplasia-specific DNA methylation markers and to design and validate a methylation marker panel for triage of high-risk human papillomavirus (hr-HPV) positive patients. First, high-throughput quantitative methylation-specific PCRs (QMSP) on a novel OpenArray™ platform, representing 424 primers of 213 cancer specific methylated genes, were performed on frozen tissue samples from 84 cervical cancer patients and 106 normal cervices. Second, the top 20 discriminating methylation markers were validated by LightCycler® MSP on frozen tissue from 27 cervical cancer patients and 20 normal cervices and ROCs and test characteristics were assessed. Three new methylation markers were identified (JAM3, EPB41L3 and TERT), which were subsequently combined with C13ORF18 in our four-gene methylation panel. In a third step, our methylation panel detected in cervical scrapings 94% (70/74) of cervical cancers, while in a fourth step 82% (32/39) cervical intraepithelial neoplasia grade 3 or higher (CIN3+) and 65% (44/68) CIN2+ were detected, with 21% positive cases for ≤CIN1 (16/75). Finally, hypothetical scenario analysis showed that primary hr-HPV testing combined with our four-gene methylation panel as a triage test resulted in a higher identification of CIN3 and cervical cancers and a higher percentage of correct referrals compared to hr-HPV testing in combination with conventional cytology. In conclusion, our four-gene methylation panel might provide an alternative triage test after primary hr-HPV testing.

Risk of borderline and invasive ovarian tumours after ovarian stimulation for in vitro fertilization in a large Dutch cohort.

BACKGROUND: Long-term effects of ovarian stimulation for IVF on the risk of ovarian malignancies are unknown. METHODS: We identified a nationwide historic cohort of 19,146 women who received IVF treatment in the Netherlands between 1983 and 1995, and a comparison group of 6006 subfertile women not treated with IVF. In 1997-1999, data on reproductive risk factors were obtained from 65% of women and data on subfertility (treatment) were obtained from the medical records. The incidence of ovarian malignancies (including borderline ovarian tumours) through 2007 was assessed through linkage with disease registries. The risk of ovarian malignancies in the IVF group was compared with risks in the general population and the subfertile comparison group. RESULTS: After a median follow-up of 14.7 years, the risk of borderline ovarian tumours was increased in the IVF group compared with the general population [standardized incidence ratio (SIR) = 1.76; 95% confidence interval (CI) = 1.16-2.56]. The overall SIR for invasive ovarian cancer was not significantly elevated, but increased with longer follow-up after first IVF (P = 0.02); the SIR was 3.54 (95% CI = 1.62-6.72) after 15 years. The risks of borderline ovarian tumours and of all ovarian malignancies combined in the IVF group were significantly increased compared with risks in the subfertile comparison group (hazard ratios = 4.23; 95% CI = 1.25-14.33 and 2.14; 95% CI = 1.07-4.25, respectively, adjusted for age, parity and subfertility cause). CONCLUSIONS: Ovarian stimulation for IVF may increase the risk of ovarian malignancies, especially borderline ovarian tumours. More large cohort studies are needed to confirm these findings and to examine the effect of IVF treatment characteristics.

The addition of GnRH antagonists in intrauterine insemination cycles with mild ovarian hyperstimulation does not increase live birth rates--a randomized, double-blinded, placebo-controlled trial.

BACKGROUND: This multicenter, double-blinded RCT investigated the efficacy of GnRH antagonists in cycles with mild ovarian hyperstimulation (MOH) followed by IUI in subfertile women. METHODS: Couples diagnosed with unexplained, male factor subfertility or associated with the presence of minimal or mild endometriosis were randomized with a computer-generated list of numbers by a third party in a double-blinded setting to receive either a GnRH antagonists or a placebo in 12 institutional or academic hospitals. All women were treated with recombinant FSH in a low-dose step-up regimen starting on Day 2-4 of the cycle. A GnRH antagonist was added when one or more follicles of 14 mm diameter or more were visualized. When at least one follicle reached a size of ≥18 mm, ovulation was induced by hCG injection. A single IUI was performed 38-40 h later. Couples were offered a maximum of three consecutive cycles. The primary outcome of the trial was live births. Secondary outcomes were pregnancy rates, multiple pregnancy rates, miscarriages and ovarian hyperstimulation syndrome rate. RESULTS: A total of 233 couples were included from January 2006 to February 2009, starting 572 treatment cycles. Live birth rates were not significantly different between the group treated with GnRH antagonist (8.4%; 23/275) and the placebo group (12%; 36/297) (P = 0.30). Three twin pregnancies occurred in the GnRH antagonist group and two twin pregnancies in the placebo group. CONCLUSIONS: Adding a GnRH antagonist in cycles with MOH in an IUI program does not increase live birth rates. Dutch Trial Register no: NTR497.

Detection of cervical neoplasia by DNA methylation analysis in cervico-vaginal lavages, a feasibility study.

OBJECTIVE: To explore the feasibility of DNA methylation analysis for the detection of cervical neoplasia in self-obtained cervico-vaginal lavages. METHODS: Lavages collected by a self-sampling device and paired cervical scrapings were obtained from 20 cervical cancer patients and 23 patients referred with an abnormal cervical smear (15 with high-grade cervical intraepithelial neoplasia (CIN2+) and 8 without CIN). All lavages and scrapings were analyzed by liquid based cytology (LBC), Hybrid Capture II (HC-II) for hr-HPV DNA detection and by DNA methylation analysis (JAM3, TERT, EPB41L3 and C13ORF18). Concordance between lavages and scrapings was measured by Cohen's Kappa (k). RESULTS: In lavages and scrapings from cervical cancer patients (n=20), methylation analysis was positive in 19 (95%) and 19 (95%), HC-II in 16 (80%) and 15 (75%) and LBC in 15 (75%) and 19 (95%), respectively. In lavages and scrapings from CIN2+ patients (n=15), methylation analysis was positive in 10 (67%) and 12 (80%), HC-II in 15 (100%) and 15 (100%) and LBC in 11 (73%) and 12 (80%), respectively. Concordance between cervical scrapings and lavages (n=43) was for LBC k=0.522 (p<0.001), hr-HPV testing k=0.551 (p<0.001) and DNA methylation analysis k=0.653 (p<0.001). CONCLUSIONS: DNA methylation analysis in cervico-vaginal lavages obtained by a self-sampling device is feasible and its diagnostic performance appears to be at least comparable to the detection of cervical neoplasia by cytomorphology and hr-HPV. Our pilot study suggests that detection of cervical neoplasia by DNA methylation analysis in cervico-vaginal lavages warrants exploration of its use in large prospective studies.

Feasibility and reliability of PRISMA-medical for specialty-based incident analysis.

AIMS AND OBJECTIVES: In this study, the feasibility and reliability of the Prevention Recovery Information System for Monitoring and Analysis (PRISMA)-Medical method for systematic, specialty-based analysis and classification of incidents in the neonatal intensive care unit (NICU) were determined. METHODS: After the introduction of a Neonatology System for Analysis and Feedback on Medical Events (NEOSAFE) in eight tertiary care NICUs and one paediatric surgical ICU, PRISMA-Medical was started to be used to identify root causes of voluntary reported incidents by multidisciplinary unit patient safety committees. Committee members were PRISMA-trained and familiar with the department and its processes. In this study, the results of PRISMA-analysis of incidents reported during the first year are described. At t = 3 months and t = 12 months after introduction, test cases were performed to measure agreement at three levels of root cause classification using PRISMA-Medical. Inter-rater reliability was determined by calculating generalised kappa values for each level of classification. RESULTS: During the study period, 981 out of 1786 eligible incidents (55%) were analysed for underlying root causes. In total, 2313 root causes were identified and classified, giving an average of 2.4 root causes for every incident. Although substantial agreement (kappa 0.70-0.81) was reached at the main level of root cause classification of the test cases (discrimination between technical, organisational and human failure) and agreement among the committees at the second level (discrimination between skill-based, rule-based and knowledge-based errors) was acceptable (kappa 0.53-0.59), discrimination between rule-based errors (the third level of classification) was more difficult to assess (kappa 0.40-0.47). CONCLUSION: With some restraints, PRISMA-Medical proves to be both feasible and acceptably reliable to identify and classify multiple causes of medical events in the NICU.

Early discharge with tube feeding at home for preterm infants is associated with longer duration of breast feeding.

OBJECTIVE: Mothers of preterm infants are more likely to discontinue breast feeding early than mothers of term infants. We evaluated the effect of early discharge with tube feeding of preterm infants under close supervision by paediatric nurse specialists on the duration of breast feeding. DESIGN: Case-control study. SETTING: Medium/high-care neonatal unit of a large district general hospital. SUBJECTS: Preterm infants (<37 weeks' gestational age). INTERVENTIONS: Early discharge with tube feeding under close supervision by paediatric nurse specialists or regular follow-up of preterm infants discharged with oral feeding. MAIN OUTCOME MEASURE: Duration of breast feeding assessed by telephone interview 6 months after birth. RESULTS: There were 50 preterm infants in the early discharge group and 78 in the control group. Mothers in the early discharge group continued to breast feed longer than mothers in the control group (log rank test, p = 0.028). Four months after discharge, 63% of preterm infants in the control group were fed formula compared to 36% in the early discharge group (95% CI for difference 9% to 43%, p = 0.04). The relative risk of breast feeding cessation 6 months after birth in the early discharge group compared to the control group was 0.63 (95% CI 0.41 to 0.96). After adjustment for smoking, gestational age and birth weight, this relative risk was 0.67 (95% CI 0.43 to 1.05). CONCLUSIONS: Close supervision and follow-up by paediatric nurse specialists of preterm infants discharged early with tube feeding appears to increase duration of breast feeding. A randomised controlled trial to confirm these findings is warranted.

Specialty-based, voluntary incident reporting in neonatal intensive care: description of 4846 incident reports.

OBJECTIVES: To examine the characteristics of incidents reported after introduction of a voluntary, non-punitive incident reporting system for neonatal intensive care units (NICUs) in the Netherlands; and to investigate which types of reported incident pose the highest risk to patients in the NICU. DESIGN: Prospective multicentre survey. METHODS: Voluntary, non-punitive incident reporting was introduced in eight level III NICUs and one paediatric surgical ICU. An incident was defined as any unintended event which (could have) reduced the safety margin for the patient. Multidisciplinary, unit-based patient safety committees systematically collected and analysed incident reports, and assigned risk scores to each reported incident. Data were centrally collected for specialty-based analysis. This paper describes the characteristics of incidents reported during the first year. Bivariate logistic regression analysis was conducted to identify high-risk incident categories. RESULTS: There were 5225 incident reports on 3859 admissions, of which 4846 were eligible for analysis. Incidents with medication were most frequently reported (27%), followed by laboratory (10%) and enteral nutrition (8%). Severe harm was described in seven incident reports, and moderate harm in 63 incident reports. Incidents involving mechanical ventilation and blood products were most likely to be assigned high-risk scores, followed by those involving parenteral nutrition, intravascular lines and medication dosing errors. CONCLUSIONS: Incidents occur much more frequently in Dutch NICUs than has been previously observed, and their impact on patient morbidity is considerable. Reported incidents concerning mechanical ventilation, blood products, intravascular lines, parenteral nutrition and medication dosing errors pose the highest risk to patients in the NICU.

The ErbB signalling pathway: protein expression and prognostic value in epithelial ovarian cancer.

Ovarian cancer is the most frequent cause of death from gynaecological cancer in the Western world. Current prognostic factors do not allow reliable prediction of response to chemotherapy and survival for individual ovarian cancer patients. Epidermal growth factor receptor (EGFR) and HER-2/neu are frequently expressed in ovarian cancer but their prognostic value remains unclear. In this study, we investigated the expression and prognostic value of EGFR, EGFR variant III (EGFRvIII), HER-2/neu and important downstream signalling components in a large series of epithelial ovarian cancer patients. Immunohistochemical staining of EGFR, pEGFR, EGFRvIII, Her-2/neu, PTEN (phosphatase and tensin homologue deleted on chromosome 10), total and phosphorylated AKT (pAKT) and phosphorylated ERK (pERK) was performed in 232 primary tumours using the tissue microarray platform and related to clinicopathological characteristics and survival. In addition, EGFRvIII expression was determined in 45 tumours by RT-PCR. Our results show that negative PTEN immunostaining was associated with stage I/II disease (P=0.006), non-serous tumour type (P=0.042) and in multivariate analysis with a longer progression-free survival (P=0.015). Negative PTEN staining also predicted improved progression-free survival in patients with grade III or undifferentiated serous carcinomas (P=0.011). Positive pAKT staining was associated with advanced-stage disease (P=0.006). Other proteins were expressed only at low levels, and were not associated with any clinicopathological parameter or survival. None of the tumours were positive for EGFRvIII. In conclusion, our results indicate that tumours showing negative PTEN staining could represent a subgroup of ovarian carcinomas with a relatively favourable prognosis.

Calcitonin therapy in central giant cell granuloma of the jaw: a randomized double-blind placebo-controlled study.

The successful therapeutic use of calcitonin in patients with a central giant cell granuloma has been shown in several case reports. In a prospective, randomized, double-blinded, placebo-controlled clinical trial, 14 patients with a histologically confirmed central giant cell granuloma and normal calcium and parathyroid hormone serum levels were studied over 2 years. Patients were treated with intranasally administered salmon calcitonin (200 IU/day) or a placebo once a day. The placebo-controlled period was 3 months, after which all patients were treated with calcitonin for 1 year. Treatment response was assessed at the end of the placebo-controlled study phase (3 months), at the end of therapy (15 months' timepoint with patients being on calcitonin treatment for either 12 or 15 months) and at 6 months' follow-up. The chi(2)-test was used to compare the proportion of patients with a tumour reduction >/=10% of the pretreatment measurement between the 2 populations at the 3 timepoints: no differences were observed between the placebo group and the calcitonin group. At the 6-month follow-up timepoint, tumour volume had decreased by >/=10% in a total of 7 patients with a 37.9% (95% CI 31.3-44.5%) mean volume reduction in this subgroup. Complete remission was not observed.

Risk of benign gynaecological diseases and hormonal disorders according to responsiveness to ovarian stimulation in IVF: a follow-up study of 8714 women.

BACKGROUND: Over the past decade, attention has been focused increasingly on the long-term health effects of IVF in women. Assuming that hormonal changes due to stimulation regimens for IVF are strongest among 'high' responders, we evaluated whether responsiveness to ovarian stimulation in IVF is predictive of the risk of benign gynaecological disorders >12 months after the last IVF cycle. METHODS: A nationwide historical cohort study of women who underwent IVF treatment was conducted. After a median time of 4.6 years following the last IVF treatment cycle, 8714 cohort members completed a health survey questionnaire that inquired about reproductive variables and the occurrence and age at onset of specific medical conditions including uterine leiomyoma, surgically removed ovarian cysts and thyroid disorders. Detailed data on cause of subfertility and IVF treatment were collected from the medical records. Women were included in the 'high responders' group when on average >/=14 oocytes were retrieved per IVF cycle (n = 1562), in the 'normal responders' group when they had a mean number of 4-13 retrieved oocytes (n = 6033), and in the 'low responders' group when they had a mean number of 0-3 retrieved oocytes per cycle (n = 1119). RESULTS: Among women with a high response to ovarian stimulation, we found a borderline significantly decreased risk of uterine leiomyoma [relative risk (RR) = 0.6; 95% confidence interval (CI) 0.4-1.0] and surgically removed ovarian cysts (RR = 0.6; 95% CI 0.3-1.0) in comparison with 'normal responders'. After OHSS, the age-adjusted RRs were 1.8 (95% CI 0.9-3.8) for having surgically removed ovarian cysts and 1.0 (95% CI 0.4-2.2) for uterine leiomyoma (both not significant). CONCLUSIONS: Despite the small number of events observed, highly elevated risks of gynaecological disorders and hormonal diseases in women undergoing IVF treatment can be excluded based on the present data and this follow-up period. Women with a low response to ovarian stimulation tended to have higher risks of benign gynaecological diseases than high responders.