Implementation of a care-pathway at the emergency department for older people presenting with nonspecific complaints; a protocol for a multicenter parallel cohort study.

BACKGROUND: Older adults frequently attend the Emergency Department (ED) with poorly defined symptoms, often called nonspecific complaints (NSC). NSC such as 'weakness' and 'not feeling well', often lead to an extensive differential diagnosis. Patients with NSC experience a prolonged length of stay at the ED and are prone to adverse outcomes. Currently, a care pathway for patients with NSC does not exist. A special structured care pathway for patients with NSC was designed to improve the efficiency and quality of care at the ED. METHOD: A multicenter parallel cohort study, organized in different hospitals in the Noord-Brabant area, the Netherlands, in which general practitioners (GP), elderly care physicians (ECP), Emergency Physicians (EP), geriatricians and internists will collaborate. Patients ≥ 70 years presenting with NSC and in need of ED admission as indicated by their own GP or ECP are eligible for inclusion. Before implementation each hospital will retrospectively include their own control-group. After implementation, patients will prospectively be included. The care-pathway exists of risk stratification by the APOP-screener, in-depth history taking, i.e. limited comprehensive geriatric assessment (CGA) and a standard set of diagnostics, and a dedicated ED-nurse (if possible) present to ensure the care-pathway is followed. The primary outcome is length of stay at the ED (LOS-ED) and perceived quality of care. Secondary outcomes are hospital length of stay, revisits, readmissions and mortality at 30- and 90-day follow-up. DISCUSSION: This study proposes a structured care pathway for older patients presenting at the ED with NSCs and considering effectiveness and perceived quality this may improve acute care for these patients. TRIAL REGISTRATION: Dutch Trial register, number NL8960.

The development of the Dutch "National model integrated care for childhood overweight and obesity".

BACKGROUND: Childhood obesity is a chronic disease with negative physical and psychosocial health consequences. To manage childhood overweight and obesity, integrated care as part of an integrated approach is needed. To realise implementation of this integrated care, practical guidance for policy and practice is needed. The aim of this study is to describe the development of a Dutch national model of integrated care for childhood overweight and obesity and accompanying materials for policy and practice. METHODS: The development of the national model was led by a university-based team in collaboration with eight selected Dutch municipalities who were responsible for the local realisation of the integrated care and with frequent input from other stakeholders. Learning communities were organised to exchange knowledge, experiences and tools between the participating municipalities. RESULTS: The developed national model describes the vision, process, partners and finance of the integrated care. It sets out a structure that provides a basis for local integrated care that should facilitate support and care for children with overweight or obesity and their families. The accompanying materials are divided into materials for policymakers to support local realisation of the integrated care and materials for healthcare professionals to support them in delivering the needed support and care. CONCLUSIONS: The developed national model and accompanying materials can contribute to improvement of support and care for children with overweight or obesity and their families, and thereby help improve the health, quality of life and societal participation of these children. Further implementation of the evidence- and practice-based integrated care while evaluating on the way is needed.

Scoping literature review and focus groups with healthcare professionals on psychosocial and lifestyle assessments for childhood obesity care.

BACKGROUND: Childhood obesity is a complex disease resulting from the interaction of multiple factors. The effective management of childhood obesity requires assessing the psychosocial and lifestyle factors that may play a role in the development and maintenance of obesity. This study centers on available scientific literature on psychosocial and lifestyle assessments for childhood obesity, and experiences and views of healthcare professionals with regard to assessing psychosocial and lifestyle factors within Dutch integrated care. METHODS: Two methods were used. First, a scoping review (in PubMed, Embase, PsycInfo, IBSS, Scopus and Web of Science) was performed by systematically searching for scientific literature on psychosocial and lifestyle assessments for childhood obesity. Data were analysed by extracting data in Microsoft Excel. Second, focus group discussions were held with healthcare professionals from a variety of disciplines and domains to explore their experiences and views about assessing psychosocial and lifestyle factors within Dutch integrated care. Data were analysed using template analysis, complemented with open coding in MAXQDA. RESULTS: The results provide an overview of relevant psychosocial and lifestyle factors that should be assessed and were classified as child, family, parental and lifestyle (e.g. nutrition, physical activity and sleep factors) and structured into psychological and social aspects. Insights into how to assess psychosocial and lifestyle factors were identified as well, including talking about psychosocial factors, lifestyle and weight; the professional-patient relationship; and attitudes of healthcare professionals. CONCLUSIONS: This study provides an overview of psychosocial and lifestyle factors that should be identified within the context of childhood obesity care, as they may contribute to the development and maintenance of obesity. The results highlight the importance of both what is assessed and how it is assessed. The results of this study can be used to develop practical tools for facilitating healthcare professionals in conducting a psychosocial and lifestyle assessment.

Performance of the MARS-crop yield forecasting system for the European Union: Assessing accuracy, in-season, and year-to-year improvements from 1993 to 2015.

19,980 crop yield forecasts have been published for the European Union (EU) Member States (MS) during 1993-2015 using the MARS-Crop Yield Forecasting System (MCYFS). We assess the performance of these forecasts for soft wheat, durum wheat, grain maize, rapeseed, sunflower, potato and sugar beet, and sought to answer three questions. First, how good has the system performed? This was investigated by calculating several accuracy indicators (e.g. the mean absolute percentage error, MAPE) for the first forecasts during a season, forecasts one month pre-harvest, and the end-of-campaign (EOC) forecasts during 2006-2015 using reported yields. Second, do forecasts improve during the season? This was evaluated by comparing the accuracy of the first, the pre-harvest, and the EOC forecasts. Third, have forecasts systematically improved year-to-year? This was quantified by testing whether linear models fitted to the median of the national level absolute relative forecast errors for each crop at EU-12 (EU-27) level from 1993 to 2015 (2006-2015) were characterized by significant negative slopes. Encouragingly, the lowest median MAPE across all crops is obtained for Europe's largest producer, France, equalling 3.73%. Similarly, the highest median MAPE is obtained for Portugal, at 14.37%. Forecasts generally underestimated reported yields, with a systematic underestimation across all MS for soft wheat, rapeseed and sugar beet forecasts. Forecasts generally improve during the growing season; both the forecast error and its variability tend to progressively decrease. This is the case for the cereals, and to a lesser extent for the tuber crops, while seasonal forecast improvements are lower for the oilseed crops. The median EU-12 yield forecasts for rapeseed, potato and sugar beet have significantly (p-value < 0.05) improved from 1993 to 2015. No evidence was found for improvements for the other crops, neither was there any significant improvement in any of the crop forecasts from 2006 to 2015, evaluated at EU-27 level. In the early years of the MCYFS, most of the yield time series were characterized by strong trends; nowadays yield growth has slowed or even plateaued in several MS. In addition, an increased volatility in yield statistics is observed, and while crop yield forecasts tend to improve in a given year, in recent years, there is no evidence of structural improvements that carry-over from year-to-year. This underlines that renewed efforts to improve operational crop yield forecasting are needed, especially in the light of the increasingly variable and occasionally unprecedented climatic conditions impacting the EU's crop production systems.

In-season performance of European Union wheat forecasts during extreme impacts.

Here we assess the quality and in-season development of European wheat (Triticum spp.) yield forecasts during low, medium, and high-yielding years. 440 forecasts were evaluated for 75 wheat forecast years from 1993-2013 for 25 European Union (EU) Member States. By July, years with median yields were accurately forecast with errors below ~2%. Yield forecasts in years with low yields were overestimated by ~10%, while yield forecasts in high-yielding years were underestimated by ~8%. Four-fifths of the lowest yields had a drought or hot driver, a third a wet driver, while a quarter had both. Forecast accuracy of high-yielding years improved gradually during the season, and drought-driven yield reductions were anticipated with lead times of ~2 months. Single, contrasting successive in-season, as well as spatially distant dry and wet extreme synoptic weather systems affected multiple-countries in 2003, '06, '07, '11 and 12', leading to wheat losses up to 8.1 Mt (>40% of total EU loss). In these years, June forecasts (~ 1-month lead-time) underestimated these impacts by 10.4 to 78.4%. To cope with increasingly unprecedented impacts, near-real-time information fusion needs to underpin operational crop yield forecasting to benefit from improved crop modelling, more detailed and frequent earth observations, and faster computation.

Word catheter and marsupialisation in women with a cyst or abscess of the Bartholin gland (WoMan-trial): a randomised clinical trial.

OBJECTIVE: To compare recurrence of a cyst or abscess of the Bartholin gland after surgical treatment using a Word catheter or marsupialisation. DESIGN: Multicentre, open-label, randomised controlled trial. SETTING: Eighteen hospitals in the Netherlands and one hospital in England. POPULATION: Women with a symptomatic cyst or abscess of the Bartholin gland. METHODS: Women were randomised to treatment with Word catheter or marsupialisation. MAIN OUTCOME MEASURES: The primary outcome was recurrence of the cyst or abscess within 1 year of treatment. The secondary outcomes included pain during and after treatment (measured on a 10-point scale), use of analgesics, and time from diagnosis to treatment. Analysis was by intention-to-treat. To assess whether marsupialisation would reduce the recurrence rate by 5% (from 20 to 15%) we needed to include 160 women (alpha error 0.05, beta error 0.2). RESULTS: One hundred and sixty-one women were randomly allocated to treatment by Word catheter (n = 82) or marsupialisation (n = 79) between August 2010 and May 2014. Baseline characteristics were comparable. Recurrence occurred in 10 women (12%) allocated to Word catheter versus eight women (10%) allocated to marsupialisation: relative risk (RR) 1.1, 95% confidence interval (CI) 0.64-1.91; P = 0.70. Pain scores after treatment were also comparable. In the first 24 hours after treatment, 33% used analgesics in the Word catheter group versus 74% in the marsupialisation group (P < 0.001). Time from diagnosis to treatment was 1 hour for placement of Word catheter versus 4 hours for marsupialisation (P = 0.001). CONCLUSIONS: In women with an abscess or cyst of the Bartholin gland, treatment with Word catheter and marsupialisation results in comparable recurrence rates. TWEETABLE ABSTRACT: Comparable recurrence rates for treatment of Bartholinic abscess/cyst with Word catheter and marsupialisation.

Polymorphic microsatellite DNA markers in the penduline tit, Remiz pendulinus.

To describe the exceptional mating system of the penduline tit, Remiz pendulinus, we aim to combine field observation records with DNA analysis based on polymorphic microsatellite DNA markers. Here we describe features of nine loci and their corresponding polymerase chain reaction primers. The observed number of alleles varied from four to seven and the observed heterozygosity ranged from 0.419 to 0.802. Neither of the loci is sex-linked and as linkage disequilibrium analysis showed they assort independently. Seven of the nine loci were polymorphic in the Cape penduline tit, Anthoscopus minutus.

Ghrelin and unacylated ghrelin stimulate human osteoblast growth via mitogen-activated protein kinase (MAPK)/phosphoinositide 3-kinase (PI3K) pathways in the absence of GHS-R1a.

Recent studies demonstrate widespread expression of ghrelin among tissues and have uncovered its pleiotropic nature. We have examined gene expression of ghrelin and its two receptor splice variants, growth hormone secretagogue receptors (GHS-R) 1a and 1b, in human bone biopsies and in the human pre-osteoblastic SV-HFO cell line during differentiation. Additionally, we examined proliferative effects of ghrelin and unacylated ghrelin (UAG) in differentiating and non-differentiating cells. We detected GHS-R1b mRNA in human bone and osteoblasts but not ghrelin's cognate receptor GHS-R1a, using two different real-time PCR assays and both total RNA and mRNA. In osteoblasts GHS-R1b mRNA expression remained low during the first 14 days of culture, but increased 300% in differentiating cells by day 21. Both human bone biopsies and osteoblasts expressed ghrelin mRNA, and osteoblasts were found to secrete ghrelin. Overall, ghrelin gene expression was greater in differentiating than non-differentiating osteoblasts, but was not increased during culture in either group. Ghrelin and UAG induced thymidine uptake dose-dependently, peaking at 1 and 10 nM respectively, at day 6 of culture in both non-differentiating and differentiating osteoblasts. The proliferative response to ghrelin and UAG declined with culture time and state of differentiation. The proliferative effects of ghrelin and UAG were suppressed by inhibitors of extracellular-signal-regulated kinase (ERK) and phosphoinositide-3 kinase, and both peptides rapidly induced ERK phosphorylation. Overall, our data suggest new roles for ghrelin and UAG in modulating human osteoblast proliferation via a novel signal transduction pathway.

Past and current gene flow in the selfing, wind-dispersed species Mycelis muralis in western Europe.

The distribution of genetic diversity in Mycelis muralis, or wall lettuce, was investigated at a European scale using 12 microsatellite markers to infer historical and contemporary forces from genetic patterns. Mycelis muralis has the potential for long-distance seed dispersal by wind, is mainly self-pollinated, and has patchily distributed populations, some of which may show metapopulation dynamics. A total of 359 individuals were sampled from 17 populations located in three regions, designated southern Europe (Spain and France), the Netherlands, and Sweden. At this within-region scale, contemporary evolutionary forces (selfing and metapopulation dynamics) are responsible for high differentiation between populations (0.34 < F(ST) < 0.60) but, contrary to expectation, levels of within-population diversity, estimated by Nei's unbiased expected heterozygosity (H(E)) (0.24 < H(E) < 0.68) or analyses of molecular variance (50% of the variation found within-populations), were not low. We suggest that the latter results, which are unusual in selfing species, arise from efficient seed dispersal that counteracts population turnover and thus maintains genetic diversity within populations. At the European scale, northern regions showed lower allelic richness (A = 2.38) than populations from southern Europe (A = 3.34). In light of postglacial colonization hypotheses, these results suggest that rare alleles may have been lost during recolonization northwards. Our results further suggest that mutation has contributed to genetic differentiation between southern and northern Europe, and that Sweden may have been colonized by dispersers originating from at least two different refugia.

Hybridization and asymmetric reproductive isolation between the closely related bryophyte taxa Polytrichum commune and P. uliginosum.

Based on genetic differentiation, the haploid dioecious bryophyte taxa Polytrichum commune and P. uliginosum have been inferred to be completely reproductively isolated. However, analysing diploid sporophytes from a sympatric population for three diagnostic microsatellite markers, we show here that reproductive isolation between these taxa is far more complex and highly asymmetric. Isolation between female-P. communex male-P. uliginosum seems to be complete and prezygotic (or early postzygotic) as no hybrid sporophytes were observed on P. commune females. In the other direction ( female-P. uliginosumx male-P. commune) isolation was clearly postzygotic as high frequencies of hybrid sporophytes were found on P. uliginosum females. However, during maturation these sporophytes showed irregular development, indicating that hybrid sporophytes are unlikely to produce ripe spores. Mechanisms possibly underlying this asymmetric reproductive isolation pattern are discussed. Notwithstanding hybrid offspring being unlikely, the high frequency of hybrid sporophytes observed suggests that viable spores may be formed occasionally through such rare processes as chromosome nondisjunction, possibly giving rise to allodiploids. Allodiploids have been reported in Polytrichum (and other bryophyte genera). Studies such as the one presented here will therefore help to elucidate the evolutionary importance of interspecific hybridization and allodiploidization in bryophyte speciation.

The reproductive biology of Polytrichum formosum: clonal structure and paternity revealed by microsatellites.

Using highly polymorphic microsatellite markers, we assessed clonal structure and paternity in a population of the bryophyte species Polytrichum formosum. Identical multilocus genotypes of individual shoots were almost never observed in spatially separated cushions, but were found to be highly clustered within moss cushions. Therefore, asexual reproduction through dispersal of gametophyte fragments is not very important in P. formosum. However, asexual reproduction on a very localized scale through vegetative growth of genets (branching of gametophytes via clonal growth of rhizomes) is very extensive. The patchy spatial distribution of genets and the absence of intermingling among genets suggest that this species follows a 'phalanx' clonal growth strategy. Vegetative proliferation of genets will increase their size, and, consequently, will have considerable fitness consequences for individuals in terms of increased genet longevity and reproductive output. Although paternity analysis of sporophytes confirmed male genet size, i.e. gamete production, to be an important determinant of male reproductive fitness, it also showed that the spatial distance to female genets is the predominant factor that governs male reproductive success. Moreover, we showed that male gamete dispersal distances in P. formosum are much further than generally assumed, and are in the order of metres rather than centimetres. Combining the findings, we conclude that the high genotypic diversity observed for this facultatively clonal species is most likely explained by a preponderance of sexual reproduction over clonal reproduction.

Amount and structure of intra- and interspecific genetic variation in the moss genus Polytrichum.

Allozyme electrophoresis was used to determine amount and structure of genetic variation within and between five congeneric haploid moss species: Polytrichum formosum, P. commune, P. uliginosum, P. piliferum and P. juniperinum. For the different species, gene diversity within populations (HS) ranged from very low (0.025) to moderate values (0.127), being, on average, lower than those observed for vascular plants and many other moss species. Polytrichum piliferum and P. juniperinum showed significantly higher levels of HS than the other species examined, which possibly might be explained by sexual reproduction being more prevalent in these two species, that often live in more dynamic habitats, where turnover of individuals is more frequent. Genetic variability was observed to be structured in contrasting ways at different levels. At the intraspecific level genetic differentiation among populations of most Polytrichum species was low, FST

Fetal cardiac dextroposition in the absence of an intrathoracic mass: sign of significant right lung hypoplasia.

We reviewed our experience of fetal cardiac dextroposition in the absence of an intrathoracic mass. Ten cases were found by fetal echocardiography to have a normal cardiac axis, but the heart was shifted into the right chest and the amount of right lung tissue was reduced. At birth seven of the infants had confirmed structural heart disease (70%), including three with scimitar syndrome. Two infants had additional extracardiac anomalies (20%). Seven infants born at term had clinical pulmonary hypertension with a diagnosis of right lung hypoplasia in all of them. Two neonates died owing to significant heart disease (one with scimitar syndrome and the other with hypoplastic left heart syndrome). Of the three pregnancies that were terminated, the two fetuses with autopsies had severe right lung hypoplasia. Fetal cardiac dextroposition and right pulmonary artery hypoplasia in the absence of an intrathoracic mass are important signs of right lung hypoplasia, which can be associated with significant pathologic cardiac and extracardiac conditions.

Echocardiographic assessment of interrupted aortic arch.

BACKGROUND: In patients with interrupted aortic arch echocardiography provides detailed information about the anatomy of the aortic arch and the associated cardiac anomalies. Only a few reports have evaluated the reliability of this non-invasive diagnostic procedure by correlation with angiographic and surgical findings. METHODS: From 1988 through 1993, 45 infants with interrupted arch underwent surgical repair (mean age 13.02 days). Of the patients, 33 had interruption of the arch between the left common carotid and subclavian arteries; 25 patients had a ventricular septal defect, and the remaining 20 had coexisting complex congenital heart defects. Preoperative diagnosis was made exclusively by echocardiography in 25 of the patients. Accuracy of echocardiographic diagnosis was evaluated retrospectively by comparing preoperative studies with angiography and surgical reports. We then investigated whether the morphologic features of the interrupted arch might influence surgical procedure or outcome. RESULTS: Intracardiac anatomy was accurately diagnosed by echocardiography in all cases; in 2 patients angiography provided additional information concerning the morphology of the aortic arch. Operative notes described differences in morphology of the arch in 7 patients, but these did not influence the surgical procedure. Direct anastomosis of the interrupted segments was possible in 38 patients, and 36 patients underwent primary intracardiac repair. Echocardiographic measurements revealed that the diameter of the ascending aorta was related to the number of vessels originating from the proximal aortic arch. The distance between the interrupted segments was significantly different according to the site of interruption, but not between cases with an isolated ventricular septal defect versus those with complex heart disease. It did not influence the method of arch repair, nor was it related to recurrent or residual obstruction. CONCLUSION: Preoperative echocardiography offers accurate and complete diagnosis in the critically ill neonate with interrupted aortic arch and associated intracardiac abnormalities.

Echocardiographic identification of thymic hypoplasia in tetralogy of fallot/tetralogy pulmonary atresia.

The use of transthoracic echocardiography to detect the presence of thymic tissue has been reported in patients at risk for graft versus host disease. We confirmed the accuracy of this method in patients with tetralogy of Fallot and tetralogy of Fallot/pulmonary atresia, and suggest using a threshold distance of 6.1 cm/m2 (5.5 to 6.3 cm/m2).

Prenatal features of ductus arteriosus constriction and restrictive foramen ovale in d-transposition of the great arteries.

BACKGROUND: Although most neonates with d-transposition of the great arteries (TGA) have an uncomplicated preoperative course, some with a restrictive foramen ovale (FO), ductus arteriosus (DA) constriction, or pulmonary hypertension may be severely hypoxemic and even die shortly after birth. Our goal was to determine whether prenatal echocardiography can identify these high-risk fetuses with TGA. METHODS AND RESULTS: We reviewed the prenatal and postnatal echocardiograms and outcomes of 16 fetuses with TGA/intact ventricular septum or small ventricular septal defect. Of the 16 fetuses, 6 prenatally had an abnormal FO (fixed position, flat, and/or redundant septum primum). Five of the 6 had restrictive FO at birth. Five fetuses had DA narrowing at the pulmonary artery end in utero, and 6 had a small DA (diameter z score of <-2.0). Of 4 fetuses with the most diminutive DA, 2 also had an abnormal appearance of the FO, and both died immediately after birth. One other fetus had persistent pulmonary hypertension. Eight fetuses had abnormal Doppler flow pattern in the DA (continuous high-velocity flow, n=1; retrograde diastolic flow, n=7). CONCLUSIONS: Abnormal features of the FO, DA, or both are present in fetuses with TGA at high risk for postnatal hypoxemia. These features may result from the abnormal intrauterine hemodynamics in TGA. A combination of restrictive FO and DA constriction in TGA may be associated with early neonatal death.

Mitral and aortic atresia associated with hypoplastic right lung, crossover segment of right lower lobe, and anomalous scimitar-like right pulmonary venous connection with inferior vena cava: clinical, angiocardiographic, and autopsy findings in a rare case.

A newborn female infant was found to have a unique and previously unreported group of anomalies: (1) mitral and aortic atresia with a highly obstructive atrial septum; (2) hypoplasia of the right lung with a crossover segment involving the right lower lobe; (3) normally connected pulmonary veins, two from the left lung and one from the right; and (4) a large anomalous branch of the right pulmonary vein of scimitar configuration that anastomosed with the normally connected right pulmonary vein and with the inferior vena cava (IVC). The scimitar vein appeared obstructed at its junction with the right pulmonary vein and at its junction with the inferior vena cava within the hepatic parenchyma. To our knowledge, this is the first report of a scimitar-like vein coexisting with mitral and aortic atresia and connecting both with the right pulmonary vein and with the inferior vena cava. The highly obstructed left atrium was partially decompressed by retrograde blood flow via the normally connected right pulmonary vein to the anomalous scimitar venous pathway and thence to the inferior vena cava via a pulmonary-to-IVC collateral vein.