Ketonuria is not associated with hyperemesis gravidarum disease severity.

OBJECTIVE: To assess the association between ketonuria and hyperemesis gravidarum (HG) disease severity. STUDY DESIGN: We included pregnant women hospitalised for HG who participated in the Maternal and Offspring outcomes after Treatment of HyperEmesis by Refeeding (MOTHER) trial and women who were eligible, chose not to be randomised and agreed to participate in the observational cohort. Between October 2013 and March 2016, in 19 hospitals in the Netherlands, women hospitalised for HG were approached for study participation. The presence of ketonuria was not required for study entry. Ketonuria was measured at hospital admission with a dipstick, which distinguishes 5 categories: negative and 1+ through 4 + . The outcome measures were multiple measures of HG disease severity at different time points: 1) At hospital admission (study entry): severity of nausea and vomiting, quality of life and weight change compared to pre-pregnancy weight, 2) One week after hospital admission: severity of nausea and vomiting, quality of life and weight change compared to admission, 3) Duration of index hospital admission and readmission for HG at any time point RESULTS: 215 women where included. Ketonuria was not associated with severity of nausea and vomiting, quality of life or weight loss at hospital admission, nor was the degree of ketonuria at admission associated with any of the outcomes 1 week after hospital admission. The degree of ketonuria was also not associated with the number of readmissions. However, women with a higher degree of ketonuria had a statistically significant longer duration of hospital stay (per 1+ ketonuria, difference: 0.27 days, 95 % CI: 0.05 to 0.48). CONCLUSIONS: There was no association between the degree of ketonuria at admission and severity of symptoms, quality of life, maternal weight loss, or number of readmissions, suggesting that ketonuria provides no information about disease severity or disease course. Despite this, women with a higher degree of ketonuria at admission were hospitalised for longer. This could suggest that health care professionals base length of hospital stay on the degree of ketonuria. Based on the lack of association between ketonuria and disease severity, we suggest it has no additional value in the clinical management of HG.

[A postpartum woman with toxic shock syndrome: group A streptococcal infection, a much feared postpartum complication.] / Een kraamvrouw met toxische-shocksyndroom.

BACKGROUND: The development of toxic shock syndrome (TSS) after an invasive group A streptococcal (GAS) infection in the postpartum period is a much feared complication. The mortality rate of TSS with necrotizing fasciitis is 30 to 50%. CASE DESCRIPTION: We present the case of a woman with atypical pelvic pain which was the first symptom of toxic shock syndrome as a consequence of a GAS infection. Clinical deterioration necessitated a hysterectomy. Also a fasciotomy was performed as consequence of lower extremity compartment syndrome. After this, multiple debridement operations were necessary, followed by split skin grafts. CONCLUSION: This case illustrates the extremely serious complications of GAS infection. In some cases aggressive surgical intervention is necessary, in addition to an optimal antibiotic treatment regime. Ideally, the treatment of a GAS-induced TSS should be managed by a multidisciplinary medical team.

Increased maternal TSH and decreased maternal FT4 are associated with a higher operative delivery rate in low-risk pregnancies: A prospective cohort study.

BACKGROUND: The increasing number of operative deliveries is a topic of major concern in modern obstetrics. Maternal thyroid function is of known influence on many obstetric parameters. Our objective was to investigate a possible relation between maternal thyroid function, and operative deliveries. Secondary aim was to explore whether thyroid function was related to specific reasons for operative deliveries. METHODS: In this prospective cohort study, low-risk Caucasian women, pregnant of a single cephalic fetus were included. Women with known auto-immune disease, a pre-labour Caesarean section, induction of labour, breech presentation or preterm delivery were excluded. In all trimesters of pregnancy the thyroid function was assessed. Differences in mean TSH and FT4 were assessed using t-test. Mean TSH and FT4 levels for operative deliveries were determined by one way ANOVA. Repeated measurement analyses were performed (ANOVA), adjusting for BMI, partiy, maternal age and gestational age at delivery. RESULTS: In total 872 women were included, of which 699 (80.2%) had a spontaneous delivery. At 36 weeks gestation women who had an operative delivery had a significantly higher mean TSH (1.63 mIU/L versus 1.46 mIU/L, p = 0.025) and lower mean FT4 (12.9 pmol/L versus 13.3 pmol/L, p = 0.007)) compared to women who had a spontaneous delivery. Mean TSH was significantly higher (p = 0.026) and mean FT4 significantly lower (p = 0.030) throughout pregnancy for women with an operative delivery due to failure to progress in second stage of labour, compared to women with a spontaneous delivery or operative delivery for other reasons. CONCLUSIONS: Increased TSH and decreased FT4 seem to be associated with more operative vaginal deliveries and Caesarean sections. After adjusting for several confounders the association remained for operative deliveries due to failure to progress in second stage of labour, possibly to be explained by less efficient uterine action.

Maternal thyrotropin is independently related to small for gestational age neonates at term.

OBJECTIVE: Small for gestational age (SGA) newborns constitute still a major cause of perinatal morbidity and mortality. Overt thyroid disease is a known cause of preterm birth and low birthweight but in its untreated condition it is rare today. In this study, we investigated the possible relation between maternal thyroid function assessed in euthyroid women at each trimester and the incidence of term born SGA neonates. DESIGN: A prospective cohort study was performed. PATIENTS: Thyroid function was assessed at 12, 24 and 36 weeks gestation in 1051 healthy Caucasian women who delivered at ≥ 37 weeks gestation. MEASUREMENTS: One-way anova was used to compare mean TSH and FT4 levels between women with SGA neonates and controls. Multiple logistic regression analysis was performed to adjust for known risk factors of SGA. RESULTS: Seventy (6·7%) SGA neonates were identified and they were significantly more often born to women with a TSH ≥ 97·5th at first and third trimester. Multiple logistic regression analysis showed that smoking (OR: 4·4, 95% CI: 2·49-7·64), pre-eclampsia (OR: 2·8, 95% CI: 1·19-6·78) and TSH ≥ 97·5th percentile (OR 3·3, 95% CI 1·39-7·53) were significantly related to SGA. Maternal FT4 levels and TPO-Ab status were not associated with SGA offspring. CONCLUSIONS: Our data show that TSH levels in the upper range of the reference interval at different trimesters (3·0-3·29 mIU/l) are independently related to an increased risk of delivering SGA neonates at term.

The aetiology of meconium-stained amniotic fluid: pathologic hypoxia or physiologic foetal ripening? (Review).

INTRODUCTION: Despite the many efforts to study the (patho)physiology of meconium release before delivery, it still remains an indistinct subject. Some studies have reported a relationship between hypoxia and MSAF, whilst others have not. The most common association found however, is between MSAF and the term of gestation. METHODS: MEDLINE, EMBASE and the Cochrane library were electronically searched. Papers about the (patho)physiology of meconium-stained amniotic fluid in English were included. Papers about management strategies were excluded (see elsewhere this issue). RESULTS: Different theories have been proposed including acute or chronic hypoxia, physiologic foetal ripening and peripartum infection. CONCLUSION: We suggest that meconium-stained amniotic fluid should be regarded as a symptom rather than a syndrome becoming more prevalent with increasing term and which might be associated with higher levels of infection or asphyxia.

Maternal thyrotrophin in euthyroid women is related to meconium stained amniotic fluid in women who deliver at or over 41 weeks of gestation.

BACKGROUND: Maternal thyroid dysfunction is of known influence on pregnancies in the preterm period. However little is known about its effect on term and post term pregnancies. Meconium stained amniotic fluid (MSAF) is known to occur preferentially in (post)term pregnancies. AIMS: To assess a possible independent relation between maternal thyroid function and MSAF. STUDY DESIGN AND SUBJECTS: 1051 women, in whom thyroid function was assessed at each trimester, were followed prospectively (delivery ≥37weeks). We compared the difference in mean TSH and FT4 between women with (152) and without (899) MSAF using one way ANOVA. Thyroid function was assessed in subgroups regarding gestational age. Finally we performed multiple logistic regression analysis with MSAF as dependent variable and TSH as independent variable adjusting for various confounders. RESULTS: Maternal thyroid function was not associated with the incidence of MSAF when analysing all deliveries ≥37weeks. However, in the "at-risk" group for MSAF (>41weeks), multiple logistic regression showed an independent relation between MSAF and TSH (O.R.: 1.61, 95% CI: 1.10-2.43). CONCLUSIONS: The present study shows that in women delivering ≥41weeks of gestation, higher TSH is independently related to MSAF.

Predicting successful intended vaginal delivery after previous caesarean section: external validation of two predictive models in a Dutch nationwide registration-based cohort with a high intended vaginal delivery rate.

OBJECTIVE: To externally validate two models from the USA (entry-to-care [ETC] and close-to-delivery [CTD]) that predict successful intended vaginal birth after caesarean (VBAC) for the Dutch population. DESIGN: A nationwide registration-based cohort study. SETTING: Seventeen hospitals in the Netherlands. POPULATION: Seven hundred and sixty-three pregnant women, each with one previous caesarean section and a viable singleton cephalic pregnancy without a contraindication for an intended VBAC. METHODS: The ETC model comprises the variables maternal age, prepregnancy body mass index (BMI), ethnicity, previous vaginal delivery, previous VBAC and previous nonprogressive labour. The CTD model replaces prepregnancy BMI with third-trimester BMI and adds estimated gestational age at delivery, hypertensive disease of pregnancy, cervical examination and induction of labour. We included consecutive medical records of eligible women who delivered in 2010. For validation, individual probabilities of women who had an intended VBAC were calculated. MAIN OUTCOME MEASURES: Discriminative performance was assessed with the area under the curve (AUC) of the receiver operating characteristic and predictive performance was assessed with calibration plots and the Hosmer-Lemeshow (H-L) statistic. RESULTS: Five hundred and fifteen (67%) of the 763 women had an intended VBAC; 72% of these (371) had an actual VBAC. The AUCs of the ETC and CTD models were 68% (95% CI 63-72%) and 72% (95% CI 67-76%), respectively. The H-L statistic showed a P-value of 0.167 for the ETC model and P = 0.356 for the CTD model, indicating no lack of fit. CONCLUSION: External validation of two predictive models developed in the USA revealed an adequate performance within the Dutch population.

Vaginal birth after a caesarean section: the development of a Western European population-based prediction model for deliveries at term.

OBJECTIVE: To develop and internally validate a model that predicts the outcome of an intended vaginal birth after caesarean (VBAC) for a Western European population that can be used to personalise counselling for deliveries at term. DESIGN: Registration-based retrospective cohort study. SETTING: Five university teaching hospitals, seven non-university teaching hospitals, and five non-university non-teaching hospitals in the Netherlands. POPULATION: A cohort of 515 women with a history of one caesarean section and a viable singleton pregnancy, without a contraindication for intended VBAC, who delivered at term. METHODS: Potential predictors for a vaginal delivery after caesarean section were chosen based on literature and expert opinions. We internally validated the prediction model using bootstrapping techniques. MAIN OUTCOME MEASURES: Predictors for VBAC. For model validation, the area under the receiver operating characteristic curve (AUC) for discriminative capacity and calibration-per-risk-quantile for accuracy were calculated. RESULTS: A total of 371 out of 515 women had a VBAC (72%). Variables included in the model were: estimated fetal weight greater than the 90(th) percentile in the third trimester; previous non-progressive labour; previous vaginal delivery; induction of labour; pre-pregnancy body mass index; and ethnicity. The AUC was 71% (95% confidence interval, 95% CI = 69-73%), indicating a good discriminative ability. The calibration plot shows that the predicted probabilities are well calibrated, especially from 65% up, which accounts for 77% of the total study population. CONCLUSION: We developed an appropriate Western European population-based prediction model that is aimed to personalise counselling for term deliveries.

A multilevel meta-analysis of single-case and small-n research on interventions for reducing challenging behavior in persons with intellectual disabilities.

The effectiveness of different interventions for challenging behavior (CB) in persons with intellectual disabilities (ID) was reviewed by means of a two-phase study. First, a systematic review of 137 meta-analyses and reviews on group-study interventions for CB in persons with ID was conducted. Based on this review, hypotheses concerning the effectiveness of divergent interventions for CB and concerning the impact of variables moderating treatment effectiveness were systematically generated. Second, these hypotheses were tested by means of a multilevel meta-analysis of single-case and small-n research. Two hundred and eighty-five studies reporting on 598 individuals were examined. The average treatment effect was large and statistically significant. However, this effect varied significantly over the included studies and participants. Compared to the meta-analyses and reviews focusing on group-studies in this research domain, the results of the present multilevel meta-analysis of single-case and small-n intervention research provided more detailed knowledge on which specific CB and intervention components moderate the interventions' effectiveness.

Neonatal thyroid screening results are related to gestational maternal thyroid function.

OBJECTIVE: To study the relationship between maternal thyroid function at each pregnancy trimester and neonatal screening results. BACKGROUND: Overt maternal thyroid dysfunction during gestation is associated with poor neonatal thyroid function. However, research on the relationship between suboptimal maternal thyroid function (assessed at three trimesters) and neonatal thyroid screening outcome is scarce. DESIGN/PATIENTS: Prospective follow-up study during three trimesters of gestation in 886 Dutch Caucasian healthy pregnant women followed from 12-week gestation until term delivery (>37 weeks) and their neonates. MEASUREMENTS: The relation between neonatal data from the Congenital Hypothyroidism (CH) screening and maternal thyroid determinants [TSH, FT4 and thyroid peroxidase (TPO)-Ab] assessed at 12-, 24- and 36-week gestation. RESULTS: Boys have lower screening TT4 levels and their mothers have higher TSH levels at 24- and 36-week gestation. Higher maternal TSH levels (>97·5th percentile, as defined in 810 women without TPO-Ab at 12 weeks) at one or more times during pregnancy (O.R: 2·26, 95% CI: 1·20-4·29) and lower gestational age (O.R: 1·22, 95% CI: 1·05-1·41) are independently related to lower screening TT4 levels. CONCLUSIONS: Maternal thyroid function during gestation is related to neonatal TT4 at screening. The finding of both lower neonatal TT4 levels in boys and higher TSH levels in mothers carrying boys is worthy of further investigation, as both observations may be meaningfully related.

High thyrotrophin levels at end term increase the risk of breech presentation.

OBJECTIVE: To study the relationship between maternal thyrotrophin (TSH) and breech presentation at term. DESIGN: Combined data sets of two prospective studies to obtain adequate epidemiological power. PATIENTS: One thousand and fifty-eight healthy pregnant women (58 breech, 1000 cephalic) and 131 women who presented in breech at an obstetrical outpatient clinic. MEASUREMENTS: Maternal thyroid parameters [TSH, free thyroid hormone (FT4), thyroid peroxidase antibody (TPO-Ab)] and foetal presentation were assessed in both groups between 35 and 38 weeks gestation. Power calculations suggested that at least 148 breech cases were required. RESULTS: The characteristics of the women in breech in both samples were similar. Women in breech (n = 58 + 131) had significantly higher TSH (but not FT4) than those (n = 1000) with cephalic presentation (Mann-Whitney U-test, P = 0·003). Different cut-offs were used to define high TSH in the 916 TPO-Ab-negative women with cephalic presentation: the 90th, 95th and 97·5th percentiles were 2·4 mIU/l (n = 149), 2·7 mIU/l (n = 77) and 3·2 mIU/l (n = 37). The prevalence rates of breech presentation in these women were all higher compared to the prevalence of breech in women below these cut-offs (df = 1, P < 0·01). The relative risk of the 149 women with a TSH >90th percentile (>2·4 mIU/l) to present in breech was 1·82 (95% CI: 1·30-2·56). CONCLUSIONS: Women with high TSH at end term are at risk for breech presentation. Substantial evidence for a relation between breech presentation and neurodevelopmental delay exists. As high TSH during gestation has also been linked to poor neurodevelopment, the relation between breech presentation and poor neurodevelopment might be thyroid-related.

Maternal thyroid function during gestation is related to breech presentation at term.

OBJECTIVE: To study the relationship between suboptimal maternal thyroid function during gestation and breech presentation at term. DESIGN: Prospective follow-up study during three trimesters of gestation. PATIENTS: A total of 1058 Dutch Caucasian healthy pregnant women were prospectively followed from 12 weeks gestation until term (>or=37 weeks) delivery. MEASUREMENTS: Maternal thyroid parameters [TSH, free T4 (FT4) and auto-antibodies to thyroid peroxidase] were assessed at 12, 24 and 36 weeks gestation as well as foetal presentation at term. RESULTS: At term, 58 women (5.5%) presented in breech. Compared with women with foetuses in the cephalic position, those women who presented in breech at term had significantly higher TSH concentrations, but only at 36 weeks gestation (P = 0.007). No between group differences were obtained for FT4 level at any assessment. The prevalence of breech presentation in the subgroup of women with TSH >or= 2.5 mIU/l (90th percentile) at 36 weeks gestation was 11%, compared with 4.8% in the women with TSH < 2.50 mIU/l (P = 0.006). Women with TSH below the 5th percentile had no breech presentations. Breech position was significantly and independently related to high maternal TSH concentration (>or=2.5 mIU/l) at 36 weeks gestation (O.R.: 2.23, 95% CI: 1.14-4.39), but not at 12 and 24 weeks gestation. CONCLUSIONS: Women with TSH levels above 2.5 mIU/l during end gestation are at risk for breech presentation, and as such for obstetric complications.

Usefulness of the Supports Intensity Scale (SIS) for persons with other than intellectual disabilities.

In response to the shift from a system-centred care model to a person-centred support model, the Supports Intensity Scale (SIS) has been developed as an instrument to assess the support needs of persons with intellectual disabilities. The instrument is used as a tool for constructing individual support plans, as well as a tool for resource allocation. The aim of the present study was to evaluate the usefulness of the SIS for persons with other than intellectual disabilities. Therefore, the psychometric properties of the SIS were investigated in a sample of 1303 persons with other than intellectual disabilities. Confirmatory factor analysis failed to support the originally proposed six-factor model within this sample. However, an explorative examination of the underlying structure resulted in a shortened version of the SIS, including four subscales and 22 items. Further analyses revealed satisfying results for reliability, construct validity, and criterion validity of the shortened assessment tool (SIS-NID).

Staff variables associated with the challenging behaviour of clients with severe or profound intellectual disabilities.

BACKGROUND: Previous research has identified that staff-client interactions play an important role in the origin and maintenance of challenging behaviour. Particularly, the reciprocity between staff behaviour and client behaviour has been considered a key issue. Furthermore, severe challenging behaviour has been found to elicit negative emotional reactions from staff which in turn may influence staff's behaviour. Another variable that has been associated with staff behaviour are staff's attributions regarding clients' challenging behaviour. The present study tested several hypotheses about associations between staff variables and challenging behaviour. METHOD: Questionnaires were used to investigate associations between the attributions, emotional reactions and behavioural reactions of 51 staff members towards challenging behaviour of clients with severe or profound intellectual disabilities who displayed self-injurious behaviour, stereotyped behaviour and/or aggressive/destructive behaviour. RESULTS: Staff members reported that reactions to challenging behaviour differed according to the type of challenging behaviour. Negative emotional reactions were positively associated with challenging behaviour. Associations between emotional reactions, staff beliefs and staff reactions were inconsistent. CONCLUSIONS: The findings suggest that there is a need to look for a better conceptualization and assessment of the variables under investigation.

Individual and classroom variables associated with relational aggression in elementary-school aged children: a multilevel analysis.

Relational aggression was studied within classroom environments by examining individual and classroom correlates among 2731 children (3rd-5th graders) during two successive measurement years. Multilevel analyses yielded small gender differences for relational aggression, indicating that such aggressive behavior was more associated with girls as compared to boys. Findings further demonstrated that relational aggression was positively associated with perceived popularity and peer rejection. Relational aggression was also found to be highly stable over time. Additionally, higher classroom aggression norms, reflected by the classroom level for relational aggression, were associated with increased relational aggression in children. Although variation in relational aggression was situated both at class- and individual-level, differences between individuals were considerably larger than differences between classes. Limitations and further research suggestions are provided and practical implications are discussed.

[Fewer caesarean sections for breech presentation following external cephalic version according to a protocol in a special office visit]. / Minder keizersneden wegens stuitligging dankzij geprotocolleerde uitwendige versie in een speciaal spreekuur.

OBJECTIVE: Identification of determinants affecting the outcome of external cephalic version (ECV) in breech presentation, and investigation of the impact of ECV--performed according to a standardized protocol in an outpatient clinic--on the mode of delivery. DESIGN: Retrospective analysis. METHOD: In 2003 a standardized protocol of ECV was developed in the outpatient clinic for obstetrics of the Catharina Hospital in Eindhoven, the Netherlands; it was tested in 'version office visits'. Obstetric characteristics of all pregnant women who underwent attempts of ECV in the clinic from January 2004 until June 2006 during these sessions, and the subsequent births, were analysed. 85% of all ECVs were performed by the same hospital midwife and gynaecologist, in accordance with the protocol. RESULTS: ECV was successful in 96 of 209 pregnant women (46%). In 1 pregnant woman an emergency caesarean section was performed after ECV because of partial abruptio placentae. Nulliparity, incomplete breech presentation and low birth weight of the baby were associated with a lower success rate of ECV in this study. In the group with a successful ECV the percentage of caesarean deliveries was substantially lower (9 versus 83%; odds ratio: 0.21; 95% CI: 0.09-0.51). CONCLUSION: A regular team consisting of a hospital midwife and a gynaecologist working according to a standardized protocol for ECV in a case of breech presentation proved successful: the number of term breech presentations substantially diminished and therefore the percentage of caesarean sections was lower in the group in which ECV had been successful. This could have considerable impact on health care in the Netherlands in terms of reduced maternal morbidity and cost savings.

Acute epiglottitis as a cause of airway obstruction in an adult patient.

Epiglottitis in adults is a dangerous infectious disease with a rising incidence and potential fatal complications as illustrated in this case report. Like in children, skilled and aggressive airway protection with appropriate antibiotic therapy have been effective in reducing mortality.

Role of the switch II region in the conformational transition of activation of Ha-ras-p21.

The role of the switch II region in the conformational transition of activation of Ha-ras-p21 has been investigated by mutating residues predicted to act as hinges for the conformational transition of this loop (Ala59, Gly60, and Gly75) (Díaz JF, Wroblowski B, Schlitter J, Engelborghs Y, 1997, Proteins 28:434-451), as well as mutating the catalytic residue Gln61. The proposed mutations of the hinge residues decrease the rate of the conformational transition of activation as measured by the binding of BeF3- to the GDP-p21 complex. Also, the thermodynamic parameters of the binding reaction are altered by a factor between three and five, depending on the temperature. (Due to changes in activation and reaction enthalpies, partially compensated by entropy changes.) The control mutation Q61H in which only the catalytic residue is changed has only a limited effect on the kinetic rate constants of the conformational transition and on the thermodynamic parameters of the reaction. The fact that mutations of the hinge residues of the switch II region affect both the binding of the phosphate analog and the conformational transition of activation indicates that the switch II is implicated both in the early and the late states of the transition.

Characterization of the hinges of the effector loop in the reaction pathway of the activation of ras-proteins. Kinetics of binding of beryllium trifluoride to V29G and I36G mutants of Ha-ras-p21.

This work experimentally confirms the pathway of activation of Ha-ras-p21, which was calculated by the method of Targeted Molecular Dynamics (TMD) (Díaz JF, Wroblowski B, Schlitter J, Engelborghs Y, 1997a, Proteins Struct Funct Genet 28:434-451). The process can be studied experimentally by analyzing the binding of BeF3- to the GDP complex of the active fluorescent mutant Y32W (Díaz JF, Sillen A, Engelborghs Y, 1997b, J Biol Chem 227:23138-23143). Two mutants, V29G and 136G, have been constructed at both sides of the effector loop of the active fluorescent mutant. This was done to check the proposed reaction pathway and to provide further insight into the mechanism of the activation of ras proteins. Both mutations accelerate the conformational isomerization with two orders of magnitude, demonstrating convincingly the role of these residues as hinges of the effector loop in one or more of the transitions of the conformational change. These results provide experimental support to the pathway calculated by TMD analysis.