Macrophage activation syndrome (MAS) is a severe, frequently fatal complication of systemic juvenile idiopathic arthritis (sJIA) with features of hemophagocytosis leading to coagulopathy, ...pancytopenia, and liver and central nervous system dysfunction. MAS is overt in 10% of children with sJIA but occurs subclinically in another 30-40%. It is difficult to distinguish sJIA disease flare from MAS. Development of criteria for establishing MAS as part of sJIA are under way and will hopefully prove sensitive and specific. Mutations in cytolytic pathway genes are increasingly being recognized in children who develop MAS as part of sJIA. Identification of these mutations may someday assist in MAS diagnosis. Defects in cytolytic genes have provided murine models of MAS to study pathophysiology and treatment. Recently, the first mouse model of MAS not requiring infection but rather dependent on repeated stimulation through Toll-like receptors was reported. This provides a model of MAS that may more accurately reflect MAS pathology in the setting of autoinflammation or autoimmunity. This model confirms the importance of a balance between pro- and anti-inflammatory cytokines. There has been remarkable progress in the use of anti-pro-inflammatory cytokine therapy, particularly against interleukin-1, in the treatment of secondary forms of MAS, such as in sJIA.
•Women with a VBAC have a higher rate of OASI.•Women with a vaginal birth after an emergency CS are the exception.•A mediolateral episiotomy reduces the OASI rate in VBAC deliveries.
Comparison of ...the rate of obstetric anal sphincter injury (OASI) between women having their first vaginal birth after caesarean section (CS) and true nulliparous women with a vaginal delivery. Assessment of risk indicators for OASI in women with vaginal birth after one CS (VBAC).
28 535 women with their first VBAC and a cohort of 275 439 nulliparous women with a vaginal delivery of a liveborn infant in a cephalic position from the Dutch perinatal registry were analyzed. We compared the OASI rate with univariate and multivariate analysis. In women with VBAC possible risk indicators for OASI were assessed using univariate and multivariate logistic regression analysis.
The rate of OASI was 5.2% in women with vaginal birth after CS and 4.0% in women with a first vaginal delivery. The adjusted OR (aOR) for vaginal birth after an elective CS was higher (aOR 1.34, 95% CI 1.23–1.47) compared to vaginal birth after an emergency CS (aOR 1.16, 95% CI 1.08–1.25). In women with vaginal birth after emergency CS, the aOR for the indication non-progressive labor was 1.18 (95% CI 1.08–1.29), whereas CS for suspected fetal distress was not significantly associated with obstetric anal sphincter injury in VBAC.
In the 28 535 women with a VBAC, mediolateral episiotomy (MLE), birth weight < 3000 g and maternal age < 25 years were associated with a significantly lower rate of OASI. A gestational age of 42 weeks, birth weight ≥ 3500 g, operative vaginal delivery and duration of the 2nd stage of labour of ≥ 60 min were associated with a significantly higher rate of OASI.
Women with a VBAC have a higher rate of OASI in comparison with women with a first vaginal delivery, with the exception of women with a vaginal birth after an emergency CS for suspected fetal distress. Factors associated with a significantly lower rate for OASI were MLE, maternal age < 25 and birth weight < 3000 g. A gestational age of 42 weeks, birth weight between 3500 and 4000 g and ≥ 4000 g, operative vaginal delivery and duration of the 2nd stage of delivery longer dan 60 min were associated with a significantly higher rate of OASI.
Objective To compare perinatal mortality and severe perinatal morbidity between planned home and planned hospital births, among low‐risk women who started their labour in primary care.
Design A ...nationwide cohort study.
Setting The entire Netherlands.
Population A total of 529 688 low‐risk women who were in primary midwife‐led care at the onset of labour. Of these, 321 307 (60.7%) intended to give birth at home, 163 261 (30.8%) planned to give birth in hospital and for 45 120 (8.5%), the intended place of birth was unknown.
Methods Analysis of national perinatal and neonatal registration data, over a period of 7 years. Logistic regression analysis was used to control for differences in baseline characteristics.
Main outcome measures Intrapartum death, intrapartum and neonatal death within 24 hours after birth, intrapartum and neonatal death within 7 days and neonatal admission to an intensive care unit.
Results No significant differences were found between planned home and planned hospital birth (adjusted relative risks and 95% confidence intervals: intrapartum death 0.97 (0.69 to 1.37), intrapartum death and neonatal death during the first 24 hours 1.02 (0.77 to 1.36), intrapartum death and neonatal death up to 7 days 1.00 (0.78 to 1.27), admission to neonatal intensive care unit 1.00 (0.86 to 1.16).
Conclusions This study shows that planning a home birth does not increase the risks of perinatal mortality and severe perinatal morbidity among low‐risk women, provided the maternity care system facilitates this choice through the availability of well‐trained midwives and through a good transportation and referral system.
To investigate trends in low Apgar scores in (near) term singletons using the Dutch Perinatal Registry.
In a cohort of 1,583,188 singletons liveborn ≥35 weeks of gestation in the period 2010-2019, we ...studied trends in low 5-min Apgar scores (<7 and <4) using Cochrane Armitage trend tests.
The proportion of infants with low Apgar scores <7 and <4 increased significantly between 2010-2019 (1.04-1.42% (p < 0.001), 0.17-0.19% (p = 0.009), respectively). Neonatal mortality remained unchanged. Induction of labour, epidural analgesia and planned caesarean section showed an increasing trend. Instrumental vaginal delivery and emergency caesarean section were performed less frequently over time, but these intervention subgroups showed the highest relative increase in infants with low Apgar scores.
In the Netherlands, the risk of a low 5-min Apgar score increased over the last decade. The highest relative increase was observed in subgroups of instrumental vaginal delivery and emergency caesarean section.
Please cite this paper as: Ravelli A, Jager K, de Groot M, Erwich J, Rijninks‐van Driel G, Tromp M, Eskes M, Abu‐Hanna A, Mol B. Travel time from home to hospital and adverse perinatal outcomes in ...women at term in the Netherlands. BJOG 2011;118:457–465.
Objective To study the effect of travel time, at the start or during labour, from home to hospital on mortality and adverse outcomes in pregnant women at term in primary and secondary care.
Design Population‐based cohort study from 2000 up to and including 2006.
Setting The Netherlands Perinatal Registry.
Population A total of 751 926 singleton term hospital births.
Methods We assessed the impact of travel time by car, calculated from the postal code of the woman’s residence to the 99 maternity units, on neonatal outcome. Logistic regression modelling with adjustments for gestational age, maternal age, parity, ethnicity, socio‐economic status, urbanisation, tertiary care centres and volume of the hospital was used.
Main outcome measures Mortality (intrapartum, and early and late neonatal mortality) and adverse neonatal outcomes (mortality, Apgar <4 and/or admission to a neonatal intensive care unit).
Results The mortality was 1.5 per 1000 births, and adverse outcomes occurred in 6.0 per 1000 births. There was a positive relationship between longer travel time (≥20 minutes) and total mortality (OR 1.17, 95% CI 1.002–1.36), neonatal mortality within 24 hours (OR 1.51, 95% CI 1.13–2.02) and with adverse outcomes (OR 1.27, 95% CI 1.17–1.38). In addition to travel time, both delivery at 37 weeks of gestation (OR 2.23, 95% CI 1.81–2.73) or 41 weeks of gestation (OR 1.52, 95% CI 1.29–1.80) increased the risk of mortality.
Conclusions A travel time from home to hospital of 20 minutes or more by car is associated with an increased risk of mortality and adverse outcomes in women at term in the Netherlands. These findings should be considered in plans for the centralisation of obstetric care.
Poly(ADP-ribose) polymerase (PARP) inhibitors represent a promising strategy toward the treatment of triple-negative breast cancer (TNBC), which is often associated to genomic instability and/or BRCA ...mutations. However, clinical outcome is controversial and no benefits have been demonstrated in wild type BRCA cancers, possibly due to poor drug bioavailability and low nuclear delivery. In the attempt to overcome these limitations, we have developed H-Ferritin nanoformulated olaparib (HOla) and assessed its anticancer efficacy on both BRCA-mutated and non-mutated TNBC cells. We exploited the natural tumor targeting of H-Ferritin, which is mediated by the transferrin receptor-1 (TfR1), and its physiological tropism toward cell nucleus. TNBC cell lines over-expressing TfR-1 were successfully recognized by H-Ferritin, displaying a fast internalization into the cells. HOla induced remarkable cytotoxic effect in cancer cells, exhibiting 1000-fold higher anticancer activity compared to free olaparib (Ola). Accordingly, HOla treatment enhanced PARP-1 cleavage, DNA double strand breaks and Ola delivery into the nuclear compartment. Our findings suggest that H-Ferritin nanoformulation strongly enhances cytotoxic efficacy of Ola as a stand-alone therapy in both BRCA-mutated and wild type TNBC cells, by promoting targeted nuclear delivery.
Please cite this paper as: de Graaf J, Ravelli A, Visser G, Hukkelhoven C, Tong W, Bonsel G, Steegers E. Increased adverse perinatal outcome of hospital delivery at night. BJOG 2010;117:1098–1107.
...Objective To determine whether delivery in the evening or at night and some organisational features of maternity units are related to perinatal adverse outcome.
Design A 7‐year national registry‐based cohort study.
Setting All 99 Dutch hospitals.
Population From nontertiary hospitals (n = 88), 655 961 singleton deliveries from 32 gestational weeks onwards, and, from tertiary centres (n = 10), 108 445 singleton deliveries from 22 gestational weeks onwards.
Methods Multiple logistic regression analysis of national perinatal registration data over the period 2000–2006. In addition, multilevel analysis was applied to investigate whether the effects of time of delivery and other variables systematically vary across different hospitals.
Main outcome measures Delivery‐related perinatal mortality (intrapartum or early neonatal mortality) and combined delivery‐related perinatal adverse outcome (any of the following: intrapartum or early neonatal mortality, 5‐minute Apgar score below 7, or admission to neonatal intensive care).
Results After case mix adjustment, relative to daytime, increased perinatal mortality was found in nontertiary hospitals during the evening (OR, 1.32; 95% CI, 1.15–1.52) and at night (OR, 1.47; 95% CI, 1.28–1.69) and, in tertiary centres, at night only (OR, 1.20; 95% CI, 1.06–1.37). Similar significant effects were observed using the combined perinatal adverse outcome measure. Multilevel analysis was unsuccessful; extending the initial analysis with nominal hospital effects and hospital–delivery time interaction effects confirmed the significant effect of night in nontertiary hospitals, whereas other organisational effects (nontertiary, tertiary) were taken up by the hospital terms.
Conclusion Hospital deliveries at night are associated with increased perinatal mortality and adverse perinatal outcome. The time of delivery and other organisational features representing experience (seniority of staff, volume) explain hospital‐to‐hospital variation.
Background: There has been a lack of appropriate classification criteria for vasculitis in children. Objective: To develop a widely accepted general classification for the vasculitides observed in ...children and specific and realistic classification criteria for common childhood vasculitides (Henoch-Schönlein purpura (HSP), Kawasaki disease (KD), childhood polyarteritis nodosa (PAN), Wegener’s granulomatosis (WG), and Takayasu arteritis (TA)). Methods: The project was divided into two phases: (1) the Delphi technique was used to gather opinions from a wide spectrum of paediatric rheumatologists and nephrologists; (2) a consensus conference using nominal group technique was held. Ten international experts, all paediatricians, met for the consensus conference. Agreement of at least 80% of the participants was defined as consensus. Results: Consensus was reached to base the general working classification for childhood vasculitides on vessel size. The small vessel disease was further subcategorised into “granulomatous” and “non-granulomatous.” Final criteria were developed to classify a child as HSP, KD, childhood PAN, WG, or TA, with changes introduced based on paediatric experience. Mandatory criteria were suggested for all diseases except WG. Conclusions: It is hoped that the suggested criteria will be widely accepted around the world because of the reliable techniques used and the international and multispecialist composition of the expert group involved.
OBJECTIVE This paper examines whether equal utilisation of health care services for first generation immigrant groups has been achieved in the Netherlands. DESIGN Survey data were linked to an ...insurance register concerning people aged 16–64. Ethnic differences in the use of a broad range of health care services were examined in this group, with and without adjustment for health status and socioeconomic status, using logistic regression. SETTING Publicly insured population in Amsterdam, the Netherlands. PARTICIPANTS 1422 people from the indigenous population, and 378 people from the four largest immigrant groups in the Netherlands—that is, the Surinamese, the Netherlands Antilleans, and the Turkish and Moroccan. MAIN OUTCOME MEASURES General practitioner service use (past two months), prescription drug use (past three months), outpatient specialist contact (past two months), hospital admission (past year), physiotherapist contact (past two months) and contact with other paramedics (past year). MAIN RESULTS Ethnicity was found to be associated with the use of health care after controlling for health status as an indicator for need. The use of general practitioner care and the use of prescribed drugs was increased among people from Surinam, Turkey and Morocco as compared with the indigenous population. Compared with the indigenous group with corresponding health status, the use of all other more specialised services was relatively low among Turkish and Moroccan people. Among the Surinamese population, the use of more specialised care was highly similar to that found in the Dutch population after differences in need were controlled for. Among people from the Netherlands Antilles, we observed a relatively high use of hospital services in combination with underuse of general practitioner services. The lower socioeconomic status of immigrant groups explained most of the increased use of the general practitioner and prescribed drugs, but could not account for the lower use of the more specialised services. CONCLUSIONS The results indicate that the utilisation of more specialised health care is lower for immigrant groups in the Netherlands, particularly for Turkish and Moroccan people and to a lesser extent, people from the Netherlands Antilles. Although underuse of more specialised services is also present among the lower socioeconomic groups in the Netherlands, the analyses indicate that this only partly explains the lower utilisation of these services among immigrant groups. This suggests that ethnic background in itself may account for patterns of consumption, potentially because of limited access.
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