Stem cell therapy for neurological disorders.

Neurological disease encompasses a diverse group of disorders of the central and peripheral nervous systems, which collectively are the leading cause of disease burden globally. The scope of treatment options for neurological disease is limited, and drug approval rates for improved treatments remain poor when compared with other therapeutic areas. Stem cell therapy provides hope for many patients, but should be tempered with the realisation that the scientific and medical communities are still to fully unravel the complexities of stem cell biology, and to provide satisfactory data that support the rational, evidence-based application of these cells from a therapeutic perspective. We provide an overview of the application of stem cells in neurological disease, starting with basic principles, and extending these to describe the clinical trial landscape and progress made over the last decade. Many forms of stem cell therapy exist, including the use of neural, haematopoietic and mesenchymal stem cells. Cell therapies derived from differentiated embryonic stem cells and induced pluripotent stem cells are also starting to feature prominently. Over 200 clinical studies applying various stem cell approaches to treat neurological disease have been registered to date (Clinicaltrials.gov), the majority of which are for multiple sclerosis, stroke and spinal cord injuries. In total, we identified 17 neurological indications in clinical stage development. Few studies have progressed into large, pivotal investigations with randomised clinical trial designs. Results from such studies will be essential for approval and application as mainstream treatments in the future.

Stem cell therapy for neurological disorders

Neurological disease encompasses a diverse group of disorders of the central and peripheral nervous systems, which collectively are the leading cause of disease burden globally. The scope of treatment options for neurological disease is limited, and drug approval rates for improved treatments remain poor when compared with other therapeutic areas. Stem cell therapy provides hope for many patients, but should be tempered with the realisation that the scientific and medical communities are still to fully unravel the complexities of stem cell biology, and to provide satisfactory data that support the rational, evidence-based application of these cells from a therapeutic perspective. We provide an overview of the application of stem cells in neurological disease, starting with basic principles, and extending these to describe the clinical trial landscape and progress made over the last decade. Many forms of stem cell therapy exist, including the use of neural, haematopoietic and mesenchymal stem cells. Cell therapies derived from differentiated embryonic stem cells and induced pluripotent stem cells are also starting to feature prominently. Over 200 clinical studies applying various stem cell approaches to treat neurological disease have been registered to date (Clinicaltrials.gov), the majority of which are for multiple sclerosis, stroke and spinal cord injuries. In total, we identified 17 neurological indications in clinical stage development. Few studies have progressed into large, pivotal investigations with randomised clinical trial designs. Results from such studies will be essential for approval and application as mainstream treatments in the future

An automated approach to the classification of impact spatter and cast-off bloodstain patterns.

In the forensic discipline of bloodstain pattern analysis, it has been suggested that there is a blurred boundary between characterising the features of a bloodstain pattern and determining the mechanism(s) that led to its deposition. This study proposes that bloodstain pattern classification can become a distinct and logical process by implementing an automated approach. To do this, an automated bloodstain pattern recognition system was developed to enable the distinction of two types of spatter bloodstain patterns. First, global pattern features based on common bloodstain pattern properties were extracted from laboratory-generated impact spatter and cast-off bloodstain patterns. Following this, automated feature selection methods were used to identify the combination of features that best distinguished the two bloodstain pattern types. This eventually led to the training and testing of a Fisher quadratic discriminant classifier using separate subsets of the generated bloodstain patterns. When applied to the training dataset, a 100% classification precision resulted. An independent dataset comprising of bloodstain patterns generated on paint and wallpaper substrates were used to validate the performance of the classifier. An error rate of 2% was obtained when the classifier was applied to these bloodstain patterns. This automated bloodstain pattern recognition system offers considerable promise as an objective classification methodology which up to now, the discipline has lacked. With further refinement, including testing it over a wider range of bloodstain patterns, it could provide valuable quantitative data to support analysts in their task of classifying bloodstain patterns.

How do late terminations of pregnancy affect comparisons of stillbirth rates in Europe? Analyses of aggregated routine data from the Euro-Peristat Project.

OBJECTIVE: To describe how terminations of pregnancy at gestational ages at or above the limit for stillbirth registration are recorded in routine statistics and to assess their impact on comparability of stillbirth rates in Europe. DESIGN: Analysis of aggregated data from the Euro-Peristat project. SETTING: Twenty-nine European countries. POPULATION: Births and late terminations in 2010. METHODS: Assessment of terminations as a proportion of stillbirths and derivation of stillbirth rates including and excluding terminations. MAIN OUTCOME MEASURES: Stillbirth rates overall and excluding terminations. RESULTS: In 23 countries, it is possible to assess the contribution of terminations to stillbirth rates either because terminations are rare occurrences or because they can be distinguished from spontaneous stillbirths. Where terminations were reported, they accounted for less than 1.5% of stillbirths at 22+ weeks in Denmark, between 13 and 22% in Germany, Italy, Hungary, Finland and Switzerland, and 39% in France. Proportions were much lower at 24+ weeks, with the exception of Switzerland (7.4%) and France (39.2%). CONCLUSIONS: Terminations represent a substantial proportion of stillbirths at 22+ weeks of gestation in some countries. Countries where terminations occur at 22+ weeks should publish rates with and without terminations in order to improve international comparisons and the policy relevance of stillbirth statistics. TWEETABLE ABSTRACT: For valid comparisons of stillbirth rates, data about late terminations of pregnancy are needed.

An eye tracking study of bloodstain pattern analysts during pattern classification.

Bloodstain pattern analysis (BPA) is the forensic discipline concerned with the classification and interpretation of bloodstains and bloodstain patterns at the crime scene. At present, it is unclear exactly which stain or pattern properties and their associated values are most relevant to analysts when classifying a bloodstain pattern. Eye tracking technology has been widely used to investigate human perception and cognition. Its application to forensics, however, is limited. This is the first study to use eye tracking as a tool for gaining access to the mindset of the bloodstain pattern expert. An eye tracking method was used to follow the gaze of 24 bloodstain pattern analysts during an assigned task of classifying a laboratory-generated test bloodstain pattern. With the aid of an automated image-processing methodology, the properties of selected features of the pattern were quantified leading to the delineation of areas of interest (AOIs). Eye tracking data were collected for each AOI and combined with verbal statements made by analysts after the classification task to determine the critical range of values for relevant diagnostic features. Eye-tracking data indicated that there were four main regions of the pattern that analysts were most interested in. Within each region, individual elements or groups of elements that exhibited features associated with directionality, size, colour and shape appeared to capture the most interest of analysts during the classification task. The study showed that the eye movements of trained bloodstain pattern experts and their verbal descriptions of a pattern were well correlated.

Effect of Wetting on Drop Splashing of Newtonian Fluids and Blood.

We investigate the impact velocity beyond which the ejection of smaller droplets from the main droplet (splashing) occurs for droplets of different liquids impacting different smooth surfaces. We examine its dependence on the surface wetting properties and droplet surface tension. We show that the splashing velocity is independent of the wetting properties of the surface but increases roughly linearly with increasing surface tension of the liquid. A preexisting splashing model and simplification are considered that predict the splashing velocity by incorporating the air viscosity. Both the splashing model and simplification give a good prediction of the splashing velocity for each surface and liquid, demonstrating the robustness of the splashing model. We also show that the splashing model can also predict the splashing velocity of blood, a shear-thinning fluid.

Defining and describing birth centres in the Netherlands - a component study of the Dutch Birth Centre Study.

BACKGROUND: During the last decade, a rapid increase of birth locations for low-risk births, other than conventional obstetric units, has been seen in the Netherlands. Internationally some of such locations are called birth centres. The varying international definitions for birth centres are not directly applicable for use within the Dutch obstetric system. A standard definition for a birth centre in the Netherlands is lacking. This study aimed to develop a definition of birth centres for use in the Netherlands, to identify these centres and to describe their characteristics. METHODS: International definitions of birth centres were analysed to find common descriptions. In July 2013 the Dutch Birth Centre Questionnaire was sent to 46 selected Dutch birth locations that might qualify as birth centre. Questions included: location, reason for establishment, women served, philosophies, facilities that support physiological birth, hotel-facilities, management, environment and transfer procedures in case of referral. Birth centres were visited to confirm the findings from the Dutch Birth Centre Questionnaire and to measure distance and time in case of referral to obstetric care. RESULTS: From all 46 birth locations the questionnaires were received. Based on this information a Dutch definition of a birth centre was constructed. This definition reads: "Birth centres are midwifery-managed locations that offer care to low risk women during labour and birth. They have a homelike environment and provide facilities to support physiological birth. Community midwives take primary professional responsibility for care. In case of referral the obstetric caregiver takes over the professional responsibility of care." Of the 46 selected birth locations 23 fulfilled this definition. Three types of birth centres were distinguished based on their location in relation to the nearest obstetric unit: freestanding (n = 3), alongside (n = 14) and on-site (n = 6). Transfer in case of referral was necessary for all freestanding and alongside birth centres. Birth centres varied in their reason for establishment and their characteristics. CONCLUSIONS: Twenty-three Dutch birth centres were identified and divided into three different types based on location according to the situation in September 2013. Birth centres differed in their reason for establishment, facilities, philosophies, staffing and service delivery.

Profiling the preterm or VLBW born adolescent; implications of the Dutch POPS cohort follow-up studies.

In 1983, data of a unique nationwide cohort of 1338 very preterm (<32 weeks of gestation) or VLBW (birth weight<1500g) infants in the Netherlands was collected and followed at several ages until they reached the age of 19 years. At 19 years of age a more extensive follow-up study was done, including questionnaires, tests on a computer and a full physical exam. These studies provide insight into how Dutch adolescents at 19 years of age, who were born very preterm or with a very low birth weight (VLBW), reach adulthood. At 19 years, 705 POPS participants participated (74% of 959 still alive). Outcome measures at 19 years included: physical outcomes (e.g. blood pressure), cognition, behavior, quality of life, and impact of handicaps. The POPS participants showed more impairments on most outcome measures at various ages, compared to norm data. Major handicaps remained stable as the children grew older, but minor handicaps and disabilities increased. At 19 years of age, only half (47.1%) of the survivors had no disabilities and no minor or major handicaps. Especially those born small for gestational age (SGA) seem most vulnerable. These long-term results help to support preterm and SGA born children and adolescents in reaching independent adulthood, and stress the need for long term follow-up studies and to promote prevention of disabilities and of preterm birth itself.

Reproductive outcomes of women and men born very preterm and/or with a very low birth weight in 1983: a longitudinal cohort study in the Netherlands.

UNLABELLED: The aims of this study were to analyze reproductive outcomes of women and men born very preterm (gestational age <32 weeks) or with a very low birth weight (<1500 g) in 1983 in the Netherlands and to compare their reproductive outcomes with the total population at a similar age of 28 years. Young adults who were born after a pregnancy complicated by very preterm (VP) delivery or with a very low birth weight (VLBW) in the Netherlands in 1983 (Project on Preterm and Small for Gestational Age Infants (POPS) cohort) were invited to complete an online questionnaire at the age of 28. In total, 293 POPS-28 participants (31.6%) completed the questionnaire including 185 female and 108 male participants. Female and male participants who were born VP or with a VLBW had significant reduced reproductive rates compared to the total Dutch population at 28 years of age (female 23.2 vs 31.9% and male 7.4 vs 22.2%). Pregnancies of the female participants were in 14% complicated by preterm delivery in at least one pregnancy. CONCLUSION: This study indicates that women and men born VP or with a VLBW have reduced reproductive rates at the age of 28 compared to the total Dutch population at a similar age.

Prenatal famine, birthweight, reproductive performance and age at menopause: the Dutch hunger winter families study.

STUDY QUESTION: Is there an association between acute prenatal famine exposure or birthweight and subsequent reproductive performance and age at menopause? SUMMARY ANSWER: No association was found between intrauterine famine exposure and reproductive performance, but survival analysis showed that women exposed in utero were 24% more likely to experience menopause at any age. WHAT IS KNOWN ALREADY: Associations between prenatal famine and subsequent reproductive performance have been examined previously with inconsistent results. Evidence for the effects of famine exposure on age at natural menopause is limited to one study of post-natal exposure. STUDY DESIGN, SIZE, DURATION: This cohort study included men and women born around the time of the Dutch famine of 1944-1945. The study participants (n = 1070) underwent standardized interviews on reproductive parameters at a mean age of 59 years. PARTICIPANTS/MATERIALS, SETTING, METHODS: The participants were grouped as men and women with prenatal famine exposure (n = 407), their same-sex siblings (family controls, n = 319) or other men and women born before or after the famine period (time controls, n = 344). Associations of famine exposure with reproductive performance and menopause were analysed using logistic regression and survival analysis with competing risk, after controlling for family clustering. MAIN RESULTS AND THE ROLE OF CHANCE: Gestational famine exposure was not associated with nulliparity, age at birth of first child, difficulties conceiving or pregnancy outcome (all P> 0.05) in men or women. At any given age, women were more likely to experience menopause after gestational exposure to famine (hazard ratio 1.24; 95% CI 1.03, 1.51). The association was not attenuated with an additional control for a woman's birthweight. In this study, there was no association between birthweight and age at menopause after adjustment for gestational famine exposure. LIMITATIONS, REASON FOR CAUTION: Age at menopause was self-reported and assessed retrospectively. The study power to examine associations with specific gestational periods of famine exposure and reproductive function was limited. WIDER IMPLICATIONS OF THE FINDINGS: Our findings support previous results that prenatal famine exposure is not related to reproductive performance in adult life. However, natural menopause occurs earlier after prenatal famine exposure, suggesting that early life events can affect organ function even at the ovarian level. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the NHLBI/NIH (R01 HL-067914). TRIAL REGISTRATION NUMBER: Not applicable.

High fat/carbohydrate ratio but not total energy intake induces lower striatal dopamine D2/3 receptor availability in diet-induced obesity.

High-energy diets that induce obesity decrease striatal dopamine D2/3 receptor (DRD2/3) availability. It is however poorly understood which components of these diets are underlying this decrease. This study assessed the role of saturated fat intake on striatal DRD2/3 availability. Forty rats were randomized to a free-choice high-fat high-sugar diet (HFHS) or a standard chow diet for 28 days. Striatal DRD2/3 availability was measured using (123)I-IBZM storage phosphor imaging at day 29. The HFHS group was split in a HFHS-high-fat (HFHS-hf) and HFHS-low-fat (HFHS-lf) group based on the percentage energy intake from fat. Rats of both HFHS subgroups had increased energy intake, abdominal fat stores and plasma leptin levels compared with controls. DRD2/3 availability in the nucleus accumbens (NAcc) was significantly lower in HFHS-hf than in HFHS-lf rats, whereas it was similar for HFHS-lf and control rats. Furthermore, DRD2/3 availability in the NAcc was positively correlated with the percentage energy intake from sugar. Total energy intake was lower for HFHS-hf than for HFHS-lf rats. Together these results suggest that a diet with a high fat/carbohydrate ratio, but not total energy intake or the level of adiposity, is the best explanation for the decrease in striatal DRD2/3 availability observed in diet-induced obesity.

Long-term results of Dutch Childhood Oncology Group studies for children with acute lymphoblastic leukemia from 1984 to 2004.

The Dutch Childhood Oncology Group (DCOG) has used two treatment strategies for children with acute lymphoblastic leukemia (ALL) based on Pinkel's St Jude Total Therapy or the Berlin-Frankfurt-Münster (BFM) backbone. In four successive protocols, 1734 children were treated. Studies ALL-6 and ALL-9 followed the Total Therapy approach; cranial irradiation was replaced by medium-dose methotrexate infusions and prolonged triple intrathecal therapy; dexamethasone was used instead of prednisone. Studies ALL-7 and ALL-8 had a BFM backbone, including more intensive remission induction, early reinduction and maintenance therapy without vincristine and prednisone pulses. The 5-year event-free survival and overall survival increased from 65.4 to 80.6% (P<0.001) and from 78.7 to 86.4% (P=0.07) in ALL-7 and ALL-9, respectively. In ALL-7 and ALL-8 National Cancer Institute (NCI) high-risk criteria, male gender, T-lineage ALL and high white blood cells (WBCs) predict poor outcome. In ALL-9 NCI criteria, gender, WBC >100 x 109/l, and T-lineage ALL have prognostic impact. We conclude that the chemotherapy-only approach in children with ALL in Total Therapy-based strategies and BFM-backbone treatment does not jeopardize survival and preserves cognitive functioning. This experience is implemented in the current DCOG-ALL-10 study using a BFM backbone and minimal residual disease-based stratification.

Dynamics of magnetic lipoplexes studied by single particle tracking in living cells.

Magnetofection, gene delivery under the influence of a magnetic field, is a technique to increase transfection efficiency by enforcing gene vector contact with a target cell. Mechanisms of magnetic lipoplex internalization and intracellular details of magnetofection are still unknown. In this study, cellular dynamics of magnetic lipoplexes were examined in real time by means of highly sensitive dual-color fluorescence microscopy. Single particle tracking of magnetic lipoplexes provided trajectories representing the movement of the lipoplexes during internalization and subsequent intracellular processes. Magnetic lipoplexes show a three-phase behavior similar to polyplexes. During phase I lipoplexes are attached to the cell surface and show slow cooperative transport behavior. Phase II takes place inside the cell and was characterized by anomalous and confined diffusion. Phase III represented active transport along microtubules inside the cell. The majority of lipoplexes were internalized via endocytosis during phase I. On later time scales the formation of a perinuclear ring was observed. Persisting colocalization of fluid phase marker and lipoplexes after 24 h indicated slow endosomal release. In short, the internalization characteristics of magnetic lipoplexes are very similar to that of polyplexes. Furthermore our results suggest that the magnetic field induces an increased concentration of magnetic complexes on the cell surface resulting in higher transfection efficiency.

[Ethnic differences in preference for home delivery and in pregnancy care received by pregnant women]. / Etnische verschillen in de voorkeur voor thuisbevallingen en het zorgtraject dat zwangeren doorlopen.

OBJECTIVE: To investigate differences among pregnant women from various ethnic groups in terms of pregnancy care and the place of delivery. DESIGN: Descriptive, retrospective study. METHOD: Data from the Dutch Perinatal Registries during the period 1995-2002, representing a total of 1,401,892 pregnancies, were linked and analysed for perinatal care, the place of the delivery and the ethnic group of the mother. The ethnic categories defined in the registries were: Dutch, Mediterranean, other European, African, Hindu, Asian and unknown. RESULTS: Other European women and Asian women often started pregnancy care with a midwife and were not often referred to secondary care with an obstetrician. These two groups most often completed the delivery under the care of a midwife (45.3% of other European women and 44.6% of Asian women). As Hindu and African women often started pregnancy care directly with an obstetrician due to medical reasons and were often referred to secondary care during pregnancy or birth, these two groups were least likely to complete their births under the primary care of a midwife (33.1% and 28.0%, respectively). 39% of the Dutch women completed delivery with a midwife. Of those women who started the delivery under the care of a midwife, 3 out of 4 Dutch women, 1 out of 3 Mediterranean women and only 1 out of 5 Hindu women ultimately elected for a home birth. CONCLUSION: Large ethnic differences exist in both pregnancy care and preference for place of delivery and, ultimately, place of birth. This should be taken into account in policy-making and in the provision of information regarding the Dutch midwifery system.

Dynamics of photoinduced endosomal release of polyplexes.

Endosomal escape is a well-known bottleneck for successful delivery of macromolecular drugs and genes. Photochemical disruption of endosomal membranes is an approach to overcome this bottleneck. In this study, we used the photosensitizer disulphonated meso-tetraphenylporphine with sulfonate groups on adjacent phenyl rings (TPPS(2a)) to investigate photoinduced endosomal release in living cells with high resolution fluorescence wide-field microscopy in real time. We studied the release dynamics of 10 kDa dextran and polyplexes consisting of DNA condensed with the cationic polymers linear polyethyleneimine (LPEI), poly-(L)-lysine (PLL) or poly-(D)-lysine (PDL). By means of dual-color microscopy and the use of double-labeled polyplexes DNA and polymer were imaged simultaneously. We show that the characteristics of the cationic polymer significantly influence the release behavior of the polyplexes. The release of dextran occurred within 100 ms. For LPEI/DNA particles, LPEI quickly spread throughout the cytosol similar to dextran, whereas DNA was released slowly (within 4 s) and remained immobile thereafter. In case of PLL particles, both DNA and polymer showed quick release. PDL particles remained condensed upon photosensitizer activation. In addition, we demonstrate that TPPS(2a) has biological side effects. Besides stop of microtubule dynamics in the dark, the movement of endosomes ceased after photosensitizer activation.

Women's motives for not participating in preconception counseling: qualitative study.

AIMS: Information about risk factors and preventive measures given before conception is estimated to prevent 15-35% of adverse pregnancy outcomes. We aimed to identify women's motives for not responding to an invitation for preconception counseling (PCC) from their general practitioner. METHODS: A purposive sample of 11 women who did not respond to an invitation for PCC and who became pregnant within 1 year was interviewed. RESULTS: Three key themes influencing nonresponse emerged from the data: perceived knowledge, perceived lack of risk and a misunderstanding of the aim of PCC. CONCLUSION: For successful future implementation of PCC, a more tailored approach may be necessary for certain (groups of) women, addressing the reasons why women do not consider themselves part of the target group for PCC.

No significant effects of single intravenous, single oral and subchronic oral administration of acetylcholinesterase inhibitors on striatal [123I]FP-CIT binding in rats.

PURPOSE: [(123)I]FP-CIT SPECT is a valuable diagnostic tool to discriminate Lewy body dementia from Alzheimer's dementia. To date, however, it is uncertain whether the frequently used acetylcholinesterase inhibitors (AChEIs) by demented patients, have an effect on [(123)I]FP-CIT binding to dopamine transporters (DATs). Earlier animal studies showed a decline of DAT availability after acute intravenous injection of AChEIs. The aim of this study was to investigate effects of single intravenous, single oral and subchronic oral administration of AChEIs on DAT availability in the rat brain as measured by [(123)I]FP-CIT. METHODS: Biodistribution studies were performed in Wistar rats (n = 5-16 per group). Before [(123)I]FP-CIT injection, rats were injected intravenously with a single dose of the AChEI rivastigmine (2.5 mg/kg body weight) or donepezil (0.5 mg/kg), the DAT-blocker methylphenidate (10 mg/kg) or saline. A second group was orally treated with a single dose of rivastigmine or donepezil (2.5 mg/kg), methylphenidate (10 mg/kg) or saline before injection of [(123)I]FP-CIT. Studies were also performed in rats that were orally treated during 14 consecutive days with either rivastigmine (1 mg/kg daily), donepezil (1.5 mg/kg daily), methylphenidate (2.5 mg/kg) or saline. Brain parts were assayed in a gamma counter, and specific striatum/cerebellum ratios were calculated for the [(123)I]FP-CIT binding to DATs. RESULTS: No significant effects of either single intravenous, single oral or subchronic oral administration of AChEIs on striatal FP-CIT binding could be detected. Single pretreatment with methylphenidate resulted in an expected significantly lower striatal FP-CIT binding. CONCLUSION: We conclude that in rats, single intravenous and single or subchronic oral administration of the tested AChEIs does not lead to an important alteration of [(123)I]FP-CIT binding to striatal DATs. Therefore, it is unlikely that these drugs will induce large effects on the interpretation of [(123)I]FP-CIT SPECT scans in routine clinical studies.

[Unexplained deaths in minors in the Amsterdam-Zaandam region in 1990-2004 and the estimated number that will be considered for further investigation into the cause of death (the NODO procedure)]. / Onverklaard overlijden bij minderjarigen in de regio Amsterdam-Zaandam, 1990-2004, en schatting van het aantal dat voor nader onderzoek naar de doodsoorzaak (NODO-procedure) in aanmerking zal komen.

OBJECTIVE: To determine how often deceased minors are examined by a forensic physician and the rate of unexplained deaths, and to estimate how often further investigation into the cause of death (the so-called NODO procedure) would be initiated. DESIGN: Descriptive, retrospective study. METHOD: Statistics Netherlands (CBS) provided the number of deceased minors and the manner as well as cause of death for the Amsterdam-Zaandam region in the period 1990-2004. Data regarding residence, age, year of death, manner of death and cause of death were collected for all post-mortem examinations performed on minors during the same period using the registration system of the Department of Forensic Medicine of the Amsterdam Municipal Health Services. RESULTS: A total of 2134 minors living in the Amsterdam-Zaandam region died in the period 1990-2004, according to the CBS. In this 15-year period the CBS registered 140 deaths (7%) that remained unexplained after post-mortem examination: 91 were registered as natural deaths due to unknown or unclear causes and 49 were registered as sudden infant death syndrome. In 306 cases (14%) the post-mortem examination was performed by municipal forensic physicians. Of these cases, 61 (20%) remained unexplained after post-mortem examination. In the remaining cases, post-mortem examination was performed by the treating physician. CONCLUSION: The estimated annual number of cases that will be referred for the NODO procedure in the Amsterdam-Zaandam region is at least 10: 4 based on unexplained deaths after examination by a municipal forensic physician and 6 based on natural deaths with no known cause of death according to the treating physician. Nationwide, at least 125 of the expected 1800 childhood deaths will be referred annually.

Increased blood loss in upright birthing positions originates from perineal damage.

OBJECTIVE: To assess whether the risk of severe blood loss is increased in semi-sitting and sitting position, and if so, to which extent blood loss from perineal damage is responsible for this finding. DESIGN: Secondary analysis of data from a large trial. SETTING: Primary care midwifery practices in the Netherlands. POPULATION: About 1646 low-risk women who had a spontaneous vaginal delivery. METHODS: Blood loss was measured using a weighing scale and measuring jug. Logistic regression analysis was used to examine the net effects of birthing position and perineal damage on blood loss greater than 500 ml. MAIN OUTCOME MEASURES: Mean total blood loss and incidence of blood loss greater than 500 ml and 1000 ml. RESULTS: Mean total blood loss and the incidence of blood loss greater than 500 ml and 1000 ml were increased in semi-sitting and sitting position. In logistic regression analysis, the interaction between birthing position and perineal damage was almost significantly associated with an increased risk of blood loss greater than 500 ml. Semi-sitting and sitting position were only significant risk factors among women with perineal damage (OR 1.30, 95% CI 1.00-1.69 and OR 2.25, 95% CI 1.37-3.71, respectively). Among women with intact perineum, no association was found. CONCLUSIONS: Semi-sitting and sitting birthing positions only lead to increased blood loss among women with perineal damage.

GP-initiated preconception counselling in a randomised controlled trial does not induce anxiety.

BACKGROUND: Preconception counselling (PCC) can reduce adverse pregnancy outcome by addressing risk factors prior to pregnancy. This study explores whether anxiety is induced in women either by the offer of PCC or by participation with GP-initiated PCC. METHODS: Randomised trial of usual care versus GP-initiated PCC for women aged 18-40, in 54 GP practices in the Netherlands. Women completed the six-item Spielberger State Trait Anxiety Inventory (STAI) before PCC (STAI-1) and after (STAI-2). After pregnancy women completed a STAI focusing on the first trimester of pregnancy (STAI-3). RESULTS: The mean STAI-1-score (n = 466) was 36.4 (95% CI 35.4-37.3). Following PCC there was an average decrease of 3.6 points in anxiety-levels (95% CI, 2.4-4.8). Mean scores of the STAI-3 were 38.5 (95% CI 37.7-39.3) in the control group (n = 1090) and 38.7 (95% CI 37.9-39.5) in the intervention group (n = 1186). CONCLUSION: PCC from one's own GP reduced anxiety after participation, without leading to an increase in anxiety among the intervention group during pregnancy. We therefore conclude that GPs can offer PCC to the general population without fear of causing anxiety.