Postpartum development of metabolic dysfunction-associated steatotic liver disease in a lean mouse model of gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is associated with increased postpartum risk for metabolic dysfunction-associated steatotic liver disease (MASLD). GDM-related MASLD predisposes to advanced liver disease, necessitating a better understanding of its development in GDM. This preclinical study evaluated the MASLD development in a lean GDM mouse model with impaired insulin secretion capacity. Lean GDM was induced by short-term 60% high-fat diet and low-dose streptozotocin injections (60 mg/kg for 3 days) before mating in C57BL/6N mice. The control dams received only high-fat diet or low-fat diet. Glucose homeostasis was assessed during pregnancy and postpartum, whereas MASLD was assessed on postpartum day 30 (PP30). GDM dams exhibited a transient hyperglycemic phenotype during pregnancy, with hyperglycaemia reappearing after lactation. Lower insulin levels and impaired glucose-induced insulin response were observed in GDM mice during pregnancy and postpartum. At PP30, GDM dams displayed higher hepatic triglyceride content compared controls, along with increased MAS (MASLD) activity scores, indicating lipid accumulation, inflammation, and cell turnover indices. Additionally, at PP30, GDM dams showed elevated plasma liver injury markers. Given the absence of obesity in this double-hit GDM model, the results clearly indicate that impaired insulin secretion driven pregnancy hyperglycaemia has a distinct contribution to the development of postpartum MASLD.

The effect of a locally tailored intervention on the uptake of preconception care in the Netherlands: a stepped-wedge cluster randomized trial (APROPOS-II study).

BACKGROUND: The preconception period provides a window of opportunity for interventions aiming to reduce unhealthy lifestyle behaviours and their negative effect on pregnancy outcomes. This study aimed to assess the effectiveness of a locally tailored preconception care (PCC) intervention in a hybrid-II effectiveness implementation design. METHODS: A stepped-wedge cluster randomized controlled trial was performed in four Dutch municipalities. The intervention contained a social marketing strategy aiming to improve the uptake (prospective parents) and the provision (healthcare providers) of PCC. Prospective parents participated by administering a questionnaire in early pregnancy recalling their preconceptional behaviours. Experiences of healthcare providers were also evaluated through questionnaires. The composite primary outcome was adherence to at least three out of four preconceptional lifestyle recommendations (early initiation of folic acid supplements, healthy nutrition, no smoking or alcohol use). Secondary outcomes were preconceptional lifestyle behaviour change, (online) reach of the intervention and improved knowledge among healthcare providers. RESULTS: A total of 850 women and 154 men participated in the control phase and 213 women and 39 men in the intervention phase. The composite primary outcome significantly improved among women participating in the municipality where the reach of the intervention was highest (Relative Risk (RR) 1.57 (95% Confidence Interval (CI) 1.11-2.22). Among women, vegetable intake had significantly improved in the intervention phase (RR 1.82 (95%CI 1.14-2.91)). The aimed online reach- and engagement rate of the intervention was achieved most of the time. Also, after the intervention, more healthcare providers were aware of PCC-risk factors (54.5% vs. 47.7%; p = 0.040) and more healthcare providers considered it easier to start a conversation about PCC (75.0% vs. 47.9%; p = 0.030). CONCLUSION: The intervention showed some tentative positive effects on lifestyle behaviours among prospective parents. Primarily on vegetable intake and the knowledge and competence of healthcare providers. The results of this study contribute to the evidence regarding successfully implementing PCC-interventions to optimize the health of prospective parents and future generations. TRIAL REGISTRATION: Dutch Trial Register: NL7784 (Registered 06/06/2019).

Continuous high-frequency pesticide monitoring to observe the unexpected and the overlooked.

Synthetic Plant Protection Products (PPPs) are a key element for a large part of today's global food systems. However, the transport of PPPs and their transformation products (TPs) to water bodies has serious negative effects on aquatic ecosystems. Small streams in agricultural catchments may experience pronounced concentration peaks given the proximity to fields and poor dilution capacity. Traditional sampling approaches often prevent a comprehensive understanding of PPPs and TPs concentration patterns being limited by trade-offs between temporal resolution and duration of the observation period. These limitations result in a knowledge gap for accurate ecotoxicological risk assessment and the achievement of optimal monitoring strategies for risk mitigation. We present here high-frequency PPPs and TPs concentration time-series measured with the autonomous MS2Field platform that combines continuous sampling and on-site measurements with a high-resolution mass spectrometer, which allows for overcoming temporal trade-offs. In a small agricultural catchment, we continuously measured 60 compounds at 20 minutes resolution for 41 days during the growing season. This observation period included 8 large and 15 small rain events and provided 2560 concentration values per compound. To identify similarities and differences among the compound-specific concentration time-series, we analysed the entire dataset with positive matrix factorisation. Six factors sufficiently captured the overall complexity in concentration dynamics. While one factor reflected dilution during rainfall, five factors identified PPPs groups that seemed to share a common history of recent applications. The investigation per event of the concentration time-series revealed a surprising complexity of dynamic patterns; physico-chemical properties of the compounds did not influence the (dis)similarity of chemographs. Some PPPs concentration peaks led while others lagged by several hours the water level peaks during large events. During small events, water level peaks always preceded concentration peaks, which were generally only observed when the water levels had almost receded to pre-event levels. Thus, monitoring schemes relying on rainfall or water level as proxies for triggering sampling may lead to systematic biases. The high temporal resolution revealed that the Swiss national monitoring integrating over 3.5 days underestimated critical concentration peaks by a factor of eight to more than 32, captured 3 out of 11 exceedances of legal acute quality standards (the relevant values in the Swiss Water Protection Law) and recorded 1 out of 9 exceedances of regulatory acceptable concentrations (the relevant values for the PPPs registration process). MS2Field allowed for observing unexpected and overlooked pesticide dynamics with consequences for further research but also for monitoring. The large variability in timing of concentration peaks relative to water level calls for more in-depth analyses regarding the respective transport mechanisms. To perform these analyses, spatially distributed sampling and time-series of geo-referenced PPPs application data are needed.

First-trimester utero-placental (vascular) development and embryonic and fetal growth: The Rotterdam periconception cohort.

INTRODUCTION: Impaired placental development is a major cause of fetal growth restriction (FGR) and early detection will therefore improve antenatal care and birth outcomes. Here we aim to investigate serial first-trimester ultrasound markers of utero-placental (vascular) development in association with embryonic and fetal growth. METHODS: In a prospective cohort, we periconceptionally included 214 pregnant women. Three-dimensional power Doppler ultrasonography at 7, 9 and 11 weeks gestational age (GA) was used to measure placental volumes (PV) and basal plate surface area by Virtual Organ Computer-aided AnaLysis™, and utero-placental vascular volume (uPVV), crown-rump length (CRL) and embryonic volume (EV) by a V-scope volume rendering application. Estimated fetal weight (EFW) was measured by ultrasound at 22 and 32 weeks GA and birth weight percentile (BW) was recorded. Linear mixed models and regression analyses were applied and appropriately adjusted. All analyses were stratified for fetal sex. RESULTS: PV trajectories were positively associated with CRL (ßadj = 0.416, 95%CI:0.255; 0.576, p < 0.001), EV (ßadj = 0.220, 95%CI:0.058; 0.381, p = 0.008) and EFW (ßadj = 0.182, 95%CI:0.012; 0.352, p = 0.037). uPVV trajectories were positively associated with CRL (ßadj = 0.203, 95%CI 0.021; 0.384, p = 0.029). In girls, PV trajectories were positively associated with CRL (p < 0.001), EV (p = 0.018), EFW (p = 0.026), and uPVV trajectories were positively associated with BW (p = 0.040). In boys, positive associations were shown between PV trajectories and CRL (p = 0.002), and between uPVV trajectories and CRL (p = 0.046). DISCUSSION: First-trimester utero-placental (vascular) development is associated with embryonic and fetal growth, with fetal sex specific modifications. This underlines the opportunity to monitor first-trimester placental development and supports the associations with embryonic and fetal growth.

Immunoglobulin A vasculitis associated with inflammatory bowel disease: a retrospective cohort study.

Objective: To describe the baseline characteristics and outcome of a series of patients with inflammatory bowel disease (IBD) and immunoglobulin A vasculitis (IgAV). Method: Patients with biopsy-proven IgAV with IBD were identified retrospectively. Data were abstracted from direct medical chart review. Each IBD-IgAV case was matched to two controls with IgAV but without IBD. Results: Nine patients were identified (seven Crohn's disease, two ulcerative colitis). Mean length of time between IBD diagnosis and IgAV onset was 17.3 ± 19.9 years. For patients on biologic treatment for IBD, mean length of time between biologic initiation and IgAV onset was 3.3 ± 3.8 years. Active IBD at IgAV onset was present in 56%. Tumour necrosis factor inhibitors (TNFi) were used for IBD in 89%. At IgAV onset, six patients were on treatment with TNFi; one subsequently discontinued, two switched to another TNFi, and three continued. At the last follow-up, three of five patients who remained on TNFi had full resolution of IgAV despite ongoing TNFi use. No differences were seen between cases with IBD IgAV and matched non-IBD-IgAV controls regarding development of end-stage renal disease, resolution of haematuria or proteinuria, and time to complete IgAV response. Conclusion: Baseline characteristics and outcomes of patients with IBD-IgAV are similar to those with IgAV without IBD. Development of IgAV is not limited to patients with clinically active IBD. Whether TNFi use is related to the pathogenesis of IgAV in some patients with IBD remains unclear. Further research into pathophysiological connections between IBD and IgAV is needed.

Incidence and predictors of thoracic aortic damage in biopsy-proven giant cell arteritis.

Objective: To describe the frequency and predisposing factors of aortic structural disease among patients with biopsy-proven giant cell arteritis (GCA).Method: A retrospective review identified all patients with biopsy-proven GCA from 1998 to 2013 with aortic imaging. Kaplan-Meier methods were used to estimate cumulative incidence and Cox models were used to examine potential predictors of development of aneurysm/dilatation of the thoracic aorta.Results: The cohort included 114 patients with aortic imaging performed within a median time of 1.8 months from GCA diagnosis. Fifty-seven patients (50%) had at least one additional follow-up imaging study. At the first imaging study, 8% had evidence of aneurysm/dilatation and 25% thickening of the thoracic aorta. Excluding prevalent cases, the cumulative incidence for aneurysm/dilatation of the thoracic aorta during follow-up was 0% at both 1 year and 2 years but increased to 10% at 5 years. The sole predictor for development of thoracic aortic aneurysm/dilatation was current smoking (hazard ratio 28.8, 95% confidence interval 1.62, 511.4; p = 0.02).Conclusion: Thoracic aortic aneurysm/dilatation was seen in 8% of patients at baseline. Among patients without aortic disease, the cumulative incidence of aortic disease was 10% at 5 years after diagnosis. Current smokers were at an increased risk for developing thoracic aortic damage. Surveillance for aortic damage should be pursued in patients with GCA, particularly those with a smoking history.

[COVID-19: recovering at home is not easy]. / Covid-19: thuis uitzieken valt niet mee.

OBJECTIVE: To gain insight into 1) the symptoms and the disease process of healthcare professionals (HCPs) who tested positive for COVID-19 and were not hospitalized because of mild symptoms, 2) the impact on their psychological well-being and 3) the experiences with (after) care and infection prevention measures. DESIGN: Explorative mixed-methods study. METHOD: The municipal public health services of Groningen and Fryslân invited all HCPs aged above 18 years who tested positive for COVID-19 between March 18th and April 3rd 2020 to fill out an online questionnaire (n = 109), on average one month after diagnosis. 18 HCPs participated in telephone interviews. RESULTS: Almost all HCPs mentioned fatigue as a long-term symptom, less frequently mentioned were, among other things, feeling physically weak and having a cold. Nearly half of them did not have a fever, two-thirds experienced stress. HCPs with comorbidity had more symptoms. The interviews showed that stress in particular occurred in families with children and because of uncertainty about the duration of infectiousness, with lack of good (after)care. Respondents experienced many negative reactions of people in their environment that felt stigmatizing. The isolation at home was considered bearable. CONCLUSION: A COVID-19 infection has a significant impact on physical and mental health, even in HCPs with mild symptoms. Persistent fatigue in particular hinders patients' functioning. The absence of fever in almost half of the respondents is remarkable, as well as the negative impact on psychological well-being. HCPs are also dissatisfied with after-care. Infection prevention measures were relatively well-adhered too.

The physiological effect of early pregnancy on a woman's response to a submaximal cardiopulmonary exercise test.

Given all its systemic adaptive requirements, pregnancy shares several features with physical exercise. In this pilot study, we aimed to assess the physiological response to submaximal cardiopulmonary exercise testing (CPET) in early pregnancy. In 20 healthy, pregnant women (<13 weeks gestation) and 20 healthy, non-pregnant women, we performed a CPET with stationary cycling during a RAMP protocol until 70% of the estimated maximum heart rate (HR) of each participant. Hemodynamic and respiratory parameters were non-invasively monitored by impedance cardiography (PhysioFlow® ) and a breath-by-breath analyzer (OxyconTM ). To compare both groups, we used linear regression analysis, adjusted for age. We observed a similar response of stroke volume, cardiac output (CO) and HR to stationary cycling in pregnant and non-pregnant women, but a slightly lower 1-min recovery rate of CO (-3.9 [-5.5;-2.3] vs. -6.6 [-8.2;-5.1] L min-1  min-1 ; p = .058) and HR (-38 [-47; -28] vs. -53 [-62; -44] bpm/min; p = .065) in pregnant women. We also observed a larger increase in ventilation before the ventilatory threshold (+6.2 [5.4; 7.0] vs. +3.2 [2.4; 3.9] L min-1  min-1 ; p < .001), lower PET CO2 values at the ventilatory threshold (33 [31; 34] vs. 36 [34; 38] mmHg; p = .042) and a larger increase of breathing frequency after the ventilatory threshold (+4.6 [2.8; 6.4] vs. +0.6 [-1.1; 2.3] breaths min-1  min-1 ; p = .015) in pregnant women. In conclusion, we observed a slower hemodynamic recovery and an increased ventilatory response to exercise in early pregnancy.

Undetected anomalies in foetuses with a prenatal diagnosis of isolated cleft.

The aim of this study was to determine the rate of undetected additional anomalies following a prenatal diagnosis of isolated oral cleft. Data of all infants with a prenatal diagnosis of isolated oral cleft born between 2000 and 2015 were studied retrospectively. Additional anomalies detected after birth were categorized as minor or major and included structural and chromosomal anomalies. Isolated clefts of the lip (CL), lip and alveolus (CLA) and lip, alveolus, and palate (CLAP) were diagnosed prenatally in 176 live-born infants. The type of cleft was more extensive after birth in 34/176 (19.3%) and less extensive in 16/176 (9.1%) newborns. Additional anomalies were diagnosed in 24 infants (13.6%), of which 12 (6.8%) were categorized as major. The latter included two submicroscopic chromosome anomalies and two gene mutations. Postnatal additional anomalies occurred more frequently in CLA and CLAP than in CL, and more in bilateral than in unilateral clefts. Major anomalies are still found in infants with a prenatal diagnosis of an isolated oral cleft. The prevalence of additional anomalies seems to be related to the type and bilaterality of the cleft, and this should be considered during prenatal counselling.

Improving recognition of potential tissue donors: a quality improvement project by a hospitalist in training in The Hague, The Netherlands.

The number of tissue donations decreased in The Netherlands over recent years. The aim of this project was to determine the number of missed tissue donors in the Haaglanden Medical Centre and to develop a strategy to improve the number of tissue donors. We retrospectively analyzed patient files of all deceased patients in 2014 for their potential as tissue donors. Our objectives were to determine the number of missed tissue donors and the percentage of correctly identified tissue donors among all physicians and hospitalists in training. In addition, a clinical audit and three focus group interviews were used to determine the level of knowledge about and adherence to local and national protocols. The findings enabled us to suggest national and local improvements to reduce the percentage of missed tissue donors. The number of missed tissue donors was 94 (17.2%) of 548 deceased patients in 2014. The percentage of correctly identified tissue donors was 65.7% among all physicians (Cohen's Kappa coefficient 0.557, p ≤ 0.001) and 57.1% among hospitalists in training (Cohen's Kappa coefficient 0.492, p ≤ 0.001). In 31 patients (32.4%), the reported contra-indication by physicians was not a contra-indication for tissue donation in The Netherlands. There was no statistical difference in correct identification between physicians and hospitalists in training (p = 0.321, Mann-Whitney). The most effective actions to increase the number of tissue donations include to better inform physicians about contra-indications and help them in the recognition of a tissue donor.

A compromised maternal vitamin D status is associated with congenital heart defects in offspring.

BACKGROUND: Interactions between genetic and environmental factors, including modifiable maternal nutrition and lifestyle, play a significant role in the pathogenesis of most congenital heart defects (CHD). The aim of this study was to investigate associations between periconceptional maternal vitamin D status and the prevalence of CHD in offspring. METHODS: A case-control study was performed in 345 mothers of a child with CHD and 432 mothers of a child without CHD from four tertiary hospitals in the Netherlands between 2003 and 2005. Approximately 15months after pregnancy mothers filled out questionnaires regarding general characteristics and periconceptional lifestyle. Maternal blood was obtained to determine serum 25-hydroxyvitamin D and lipid concentrations. The 25-hydroxyvitamin D concentration was stratified into a deficient <50nmol/l, moderate 50-75nmol/l and adequate >75nmol/l status. Logistic regression was performed to study associations between vitamin D status and CHD risk, adjusted for maternal age, body mass index, ethnicity, smoking and total cholesterol concentration. RESULTS: Case mothers less often had an adequate vitamin D status compared with controls (27% vs. 38%; p=0.002). The use of multivitamin supplements, ethnicity, season and body mass index were associated with vitamin D concentrations. A moderate (odds ratio 1.58, [95%CI 1.08, 2.32]) and deficient (odds ratio 2.15, [95%CI 1.44-3.19]) vitamin D status were associated with CHD in offspring. CONCLUSION: A compromised maternal vitamin D status is associated with an approximately two-fold increased prevalence of CHD in offspring. Therefore, improvement of the periconceptional maternal vitamin D status is recommended.

New imaging markers for preconceptional and first-trimester utero-placental vascularization.

INTRODUCTION: The availability of imaging makers of early placental circulation development is limited. This study aims to develop a feasible and reliable method to assess preconceptional and early first-trimester utero-placental vascular volumes using three-dimensional power Doppler (3D PD) ultrasound on two different Virtual Reality (VR) systems. METHODS: 3D PD ultrasound images of the uterine and placental vasculature were obtained in 35 women, either preconceptionally (n = 5), or during pregnancy at 7 (n = 10), 9 (n = 10) or 11 (n = 10) weeks of gestation. Preconceptional uterine vascular volume (UVV), first-trimester placental vascular volume (PVV) and embryonic vascular volume (EVV) were measured by two observers on two VR systems, i.e., a Barco I-Space and VR desktop. Intra- and inter-observer agreement and intersystem agreement were assessed by intra-class correlation coefficients (ICC) and absolute and relative differences. RESULTS: Uterine-, embryonic- and placental vascular volume measurements showed good to excellent intra- and inter-observer agreement and inter-system reproducibility with most ICC above 0.80 and relative differences of less than 20% preconceptionally and almost throughout the entire gestational age range. Inter-observer agreement of PVV at 11 weeks gestation was suboptimal (ICC 0.69, relative difference 50.1%). DISCUSSION: Preconceptional and first-trimester 3D PD ultrasound utero-placental and embryonic vascular volume measurements using VR are feasible and reliable. Longitudinal cohort studies with repeated measurements are needed to further validate this and assess their value as new imaging markers for placental vascular development and ultimately for the prediction of placenta-related pregnancy complications.

Parental perspectives on the awareness and delivery of preconception care.

BACKGROUND: The attention for Preconception Care (PCC) has grown substantially in recent years, yet the implementation of PCC appears challenging as uptake rates remain low. The objective of this study was to assess parental perspectives on how PCC should be provided. METHODS: Recruitment of participants took place among couples who received antenatal care at a Dutch community midwifery practice. Between June and September 2014, five focus group sessions were held with 29 women and one focus group session with 5 men. Thematic analysis was conducted using NVivo 10 software. RESULTS: Participants were generally unfamiliar with the concept of PCC. It was proposed to raise awareness by means of a promotional campaign, stipulating that PCC is suited for every couple with a (future) child wish. Suggestions were made to display marketing materials in both formal and informal (local community) settings. Addressing existing social networks and raising social dialogue was expected to be most efficient. It was recommended to make PCC more accessible by offering multiple forms and to involve male partners. Opportunistic offering PCC by healthcare providers was considered more acceptable when the subject was deliberately raised, for example while discussing contraceptives, lifestyle risks or drug prescriptions. GP's or midwifes were regarded the most suitable PCC providers, however provider characteristics such as experience, empathy and communication skills were considered more important. CONCLUSIONS: This study showed that from the parental perspective it is recommended to address every couple with a (future) child wish by means of enlarging the awareness and accessibility of PCC. In order to enlarge the awareness, it is recommended to address social networks, to raise the social dialogue and to conduct promotional campaigns regarding PCC. In order to improve the accessibility of PCC, it was suggested to simultaneously offer multiple forms: group sessions, individual consultations, walk-in-hours and online sessions, and to involve male partners.

Recombinant human adenovirus-5 expressing capsid proteins of Indian vaccine strains of foot-and-mouth disease virus elicits effective antibody response in cattle.

Recombinant adenovirus-5 vectored foot-and-mouth disease constructs (Ad5- FMD) were made for three Indian vaccine virus serotypes O, A and Asia 1. Constructs co-expressing foot-and- mouth disease virus (FMDV) capsid and viral 3C protease sequences, were evaluated for their ability to induce a neutralizing antibody response in indigenous cattle (Bos indicus). Purified Ad5-FMD viruses were inoculated in cattle as monovalent (5×109 pfu/animal) or trivalent (5×109 pfu/animal per serotype) vaccines. Animals vaccinated with monovalent Ad5-FMD vaccines were boosted 63days later with the same dose. After primary immunization, virus neutralization tests (VNT) showed seroconversion in 83, 67 and 33% of animals vaccinated with Ad5-FMD O, A and Asia 1, respectively. Booster immunization elicited seroconversion in all of the animals (100%) in the monovalent groups. When used in a trivalent form, the Ad5-FMD vaccine induced neutralizing antibodies in only 33, 50 and 16% of animals against serotypes O, A and Asia 1, respectively on primo-vaccination, and titers were significantly lower than when the same vectors were used in monovalent form. Neutralizing antibody titers differed by serotype for both Ad5-FMD monovalent and trivalent vaccines, with Asia 1 serotype inducing the lowest titers. Antibody response to Ad5 vector in immunized cattle was also assessed by VNT. It appeared that the vector immunity did not impact the recall responses to expressed FMDV antigens on booster immunization. In summary, the study suggested that the recombinant Ad5-FMD vaccine has a potential use in monovalent form, while its application in multivalent form is not currently encouraging.

Healthcare providers' views on the delivery of preconception care in a local community setting in the Netherlands.

BACKGROUND: The attention for preconception care (PCC) has grown substantially in recent years, yet PCC is far from routine in daily practice. One of the major challenges for the implementation of PCC is to identify how it can best be organized and provided within the primary care setting. The aim of this study was to identify bottlenecks and solutions for the delivery of PCC from a healthcare providers' perspective in a local community setting in the Netherlands. METHODS: Health professionals within the region of Zeist, the Netherlands, were invited for a meeting on the local implementation of PCC. Five parallel group sessions were held with 30 participants from different disciplines. The sessions were moderated based on the Nominal Group Technique, in which bottlenecks (step 1) and solutions (step 2) for the delivery of PCC were gathered, categorized and prioritized by the participants. RESULTS: Participants expressed that the provision of PCC is challenging due to lack of awareness, the absence of a costing structure and unclear allocation of responsibilities. The most pragmatic approach considered was to make interdisciplinary arrangements within the local primary care setting. Participants recommended to 1) settle a costing structure by means of third party reimbursement, 2) improve collaboration by means of a local cooperation network and an adequate referral system, 3) invest in education, tools and logistics and 4) increase uptake rates by the routine opportunistic offer of PCC and promotional campaigns. CONCLUSIONS: From a provider's perspective a tailored approach is advocated in which interdisciplinary arrangements for collaboration and referral are set up within the local primary care setting.

Cumulative changes in weight but not fluid volume balances reflect fluid accumulation in ICU patients.

BACKGROUND: The cumulative fluid balance of critically ill patients seems to be an outcome-relevant variable. However, there are no validated data for their reliability calculated for longer (> 5 days) periods of time. METHODS: All ICU patients ≥ 18 years, with an ICU stay ≥ 5 days and a body weight ≤ 195 kg were evaluated from 1 January 2013 to 31 December 2013. Daily standardized weighing was performed using bed-integrated scales simultaneously with the daily 24-h fluid balance. Simultaneously, a fluid balance without and with insensible perspiration (10 ml/kg/day) was calculated for each 24 h. Primary endpoint: difference between cumulative fluid balance and body weight changes at the day of transfer to the normal ward or the day of death in the ICU, respectively, in each patient. All data are presented as medians with interquartile ranges (IQR) with 25 and 75 percentiles (IQR/25/75) unless otherwise noted. RESULTS: One hundred and six critically ill patients were evaluated; 82 survivors and 24 nonsurvivors. Cumulative 24-h fluid balances rose continuously while body weight decreased over time. Correction of cumulative fluid balances for insensible perspiration (10 ml/kg/day) also did not match with body weight changes. Only survivors had a significant loss in body weight -1.8 (27.5/-6.1/1.0) kg. CONCLUSIONS: Assuming that changes in body weight reflect changes in whole body water content cumulative daily fluid volume balances without or with correction for insensible water loss are not useful for estimating cumulative fluid balance of ICU patients. Survivors but not nonsurvivors had a significant loss of weight over time.

Effect of signal acquisition method on the fetal heart rate analysis with phase rectified signal averaging.

Phase rectified signal averaging (PRSA) is increasingly used for fetal heart rate (FHR) monitoring, both with traces acquired with external Doppler cardiotocography (D-FHR), and with transabdominal fetal electrocardiography (ta-FHR). However, it is unclear to what extend the acquisition method influences the PRSA analysis, whether results from using one acquisition method are comparable to those based on FHR acquired by the other method, and if not, which should be the preferred method. To address these questions, we applied PRSA analysis to 28 antepartum synchronous recordings of the FHR using simultaneously D-FHR and ta-FHR. The data included late-onset intrauterine growth restricted (IUGR) fetuses (n = 20) and non-IUGR fetuses (n = 8), all of them at gestation ⩾34 weeks. PRSA analysis depends on two parameters intrinsic to the algorithm, T and S. We analyzed the data using parameters that included all values adopted by other researchers previously (derived from a literature search in PubMed and Google Scholar). T and S were adjusted for the difference in acquisition techniques. We found that the correlation between PRSA analysis based on D-FHR and ta-FHR decreased with decreasing values of the PRSA parameters T and S. Therefore, the acquisition technique affects PRSA values for high resolution PRSA (low values of T and S). In conclusion, for low resolution PRSA, the results from both acquisition methods are comparable. Because ta-FHR signals provide beat to beat data and thus capture more subtle differences in the heart rate variation than D-FHR signals (pre-processed by commercial monitors), we assumed that ta-FHR may provide potentially valuable extra information compared to D-FHR. However, no parameter settings or acquisition method seemed to have a diagnostic value for identifying the late-onset IUGR babies in our dataset.

[An Analysis of contributions to the main German chat forum for cancer patients regarding palliative care]. / Analyse von Beiträgen im größten deutschen Chatforum für Tumorpatienten zum Thema Palliativmedizin.

INTRODUCTION: Patients are looking for information regarding palliative care in different sources. Goal of this study is the analysis of the most important online forum for cancer patients, Cancer Compass, concerning palliative care. METHODOLOGY: On the chosen date, 3.02.2012, all threads on the various topics (cancer types, cancer treatment, specific user groups, general topics, advice and addresses, countries and regions, Über den Krebs-Kompass & Vermischtes) were systematically analyzed. All entries relating to palliative care were recorded and subsequently analyzed and summarized. RESULTS: From 231 threads relating to palliative care, 163 were relevant.The general practitioner is the main source of information, but the internet is gaining importance. The forum users often offer good explanations of cancer and palliative care and also refer to web pages with exact definitions. Reliability of web pages is a one issue discussed in the forum.Patients are afraid of pain and dying. Relatives fear for the patient, are overwhelmed and experience existential problems. Both groups use the Cancer Compass to share experiences and get psychological support. Thus Cancer Compass offers a possibility to discuss options for improving quality of life.Especially in the initial phase of care, many users are uncertain what palliative care means. The treatment of pain represents the main concern of patients and their families. Whereas dedicated palliative care wards are rated positively, users speak less positively about pain treatment in general wards in home care.In general, inpatient palliative care was rated positively. However information regarding outpatient care is lacking. Family care is mostly not possible on account of geographical distance. One point of criticism is the discrepancy between urban and rural areas. Patients place more trust in their general practitioner than in hospital doctors. CONCLUSION: Cancer Compass is an important medium for patients and their families to share information, i. a. on palliative care. In order to improve the reliability of information from the internet, a certification of websites would be helpful. In web forums moderators may improve the quality of information.

Androgen levels in women with various forms of ovarian dysfunction: associations with cardiometabolic features.

STUDY QUESTION: Are differences in androgen levels among women with various forms of ovarian dysfunction associated with cardiometabolic abnormalities? SUMMARY ANSWER: Androgen levels differed substantially between women with and without ovarian dysfunction, and increased androgen levels were associated with impaired cardiometabolic features in all women irrespective of their clinical condition. WHAT IS KNOWN ALREADY: Sex steroid hormones play important roles in the development of cardiovascular diseases (CVD). Extremes of low as well as high androgen levels have been associated with increased CVD risk in both men and women. STUDY DESIGN, SIZE, DURATION: This cross-sectional study included 680 women with polycystic ovary syndrome (PCOS), premature ovarian insufficiency (POI), natural post-menopausal women (NM), or regular menstrual cycles (RC) (170 women per group). PARTICIPANTS/MATERIALS, SETTING, METHODS: Measurements of serum testosterone, androstenedione and dehydroepiandrosterone sulfate were performed using liquid chromatography-tandem mass spectrometry. Assessments were taken of body mass index (BMI), blood pressure, lipid profiles, glucose, insulin and SHBG, and the bioactive fraction of circulating testosterone was calculated using the free androgen index (FAI). MAIN RESULTS AND THE ROLE OF CHANCE: PCOS women were hyperandrogenic [median FAI = 4.9 (IQR 3.6-7.4)], and POI women were hypoandrogenic [FAI = 1.2 (0.8-1.7)], compared with RC women [FAI = 1.7 (1.1-2.8)], after adjustment for age, ethnicity, smoking and BMI (P < 0.001). After adjustment for age, there were no significant differences in androgens between POI and NM (P = 0.15) women and between NM and RC (P = 0.27) women, the latter indicating that chronological aging rather than ovarian aging influences the differences between pre- and post-menopausal women. A high FAI was associated with elevated triglycerides (ß log FAI for PCOS: 0.45, P < 0.001, POI: 0.25, P < 0.001, NM: 0.20, P = 0.002), insulin (ß log FAI for PCOS: 0.77, POI: 0.44, NM: 0.40, all P < 0.001), HOMA-IR (ß log FAI for PCOS: 0.82, POI: 0.46, NM: 0.47, all P < 0.001) and mean arterial pressure (ß log FAI for PCOS: 0.05, P = 0.002, POI: 0.07, P < 0.001, NM: 0.04, P = 0.04) in all women; with increased glucose (ß log FAI for PCOS: 0.05, P = 0.003, NM: 0.07, P < 0.001) and decreased high-density lipoprotein (ß log FAI for PCOS: -0.23, P < 0.001, NM: -0.09, P = 0.03) in PCOS and NM women; and with increased low-density lipoprotein (ß log FAI for POI: 0.083, P = 0.041) in POI women. Adjustment for BMI attenuated the observed associations. Associations between FAI and cardiometabolic features were the strongest in PCOS women, even after adjustment for BMI. LIMITATIONS, REASONS FOR CAUTION: Associations between androgen levels and cardiometabolic features were assessed in PCOS, POI and NM women only, due to a lack of available data in RC women. Due to the cross-sectional design of the current study, the potential associations between androgen levels and actual future cardiovascular events could not be assessed. WIDER IMPLICATIONS OF THE FINDINGS: This study affirms the potent effect of androgens on cardiometabolic features, indicating that androgens should indeed be regarded as important denominators of women's health. Future research regarding the role of androgens in the development of CVD and potential modulatory effects of BMI is required. STUDY FUNDING/COMPETING INTERESTS: N.M.P.D. is supported by the Dutch Heart Foundation (grant number 2013T083). L.J. and O.H.F. work in ErasmusAGE, a center for aging research across the life course, funded by Nestlé Nutrition (Nestec Ltd), Metagenics Inc. and AXA. M.K. is supported by the AXA Research Fund. Nestlé Nutrition (Nestec Ltd), Metagenics Inc. and AXA had no role in the design and conduct of the study; the collection, management, analysis and interpretation of the data; or the preparation, review or approval of the manuscript. J.S.E.L. has received fees and grant support from the following companies (in alphabetical order): Ferring, Merck-Serono, Merck Sharpe & Dome, Organon, Schering Plough and Serono. In the last 5 years, B.C.J.M.F. has received fees and grant support from the following companies (in alphabetic order); Actavis, COGI, Euroscreen, Ferring, Finox, Genovum, Gedeon-Richter, Merck-Serono, OvaScience, Pantharei Bioscience, PregLem, Roche, Uteron and Watson laboratories. With regard to potential conflicts of interest, there is nothing further to disclose.

Biopsy techniques to study the human placental bed.

BACKGROUND: The physiologic transformation of uterine spiral arteries in the human placental bed is essential for a healthy pregnancy. Failure of this transformation due to deficient trophoblast invasion is widely believed to underlie pregnancy complications such as preeclampsia, foetal growth restriction, miscarriage and preterm labour. Understanding of invasive behaviour and remodelling properties of trophoblasts in the uterine wall is essential in elucidating the aetiology of these pregnancy complications. However, there is a lack of satisfactory specimens of the placental bed to enhance our knowledge on the mechanisms that control trophoblast invasion. Several techniques can be used to obtain biopsies from the placental bed and sample handling can be executed differently depending on the research question. METHODS: This systematic review provides an overview of all studies investigating the placental bed and sampling techniques used. Papers that described surgical techniques, specimen handling, complications and/or success rate of the placental bed biopsy procedures were included. Placental bed biopsies are an essential and feasible technique to study abnormalities in the placental bed associated with pregnancy complications. RESULTS: Depending on the technique used the likelihood of sampling a spiral artery and trophoblast from the placental bed is 51%-78% per case, without significant complications. CONCLUSIONS: Caution is needed when interpreting data if the placental bed is subjected to labour. We propose a uniform sampling technique and conservation protocol for the study of the placental bed and provide tools for selection of the appropriate technique for future placental bed collections.