The Postoperative Morbidity Survey was validated and used to describe morbidity after major surgery.

OBJECTIVES: To describe the reliability and validity of the Postoperative Morbidity Survey (POMS). To describe the level and pattern of short-term postoperative morbidity after major elective surgery using the POMS. STUDY DESIGN AND SETTING: This was a prospective cohort study of 439 adults undergoing major elective surgery in a UK teaching hospital. The POMS, an 18-item survey that address nine domains of postoperative morbidity, was recorded on postoperative days 3, 5, 8, and 15. RESULTS: Inter-rater reliability was perfect for 11/18 items (Kappa=1.0), with Kappa=0.94 for 6/18 items. A priori hypotheses that the POMS would discriminate between patients with known measures of morbidity risk, and predict length of stay were generally supported through observation of data trends, and there was statistically significant evidence of construct validity for all but the wound and neurological domains. POMS-defined morbidity was present in 325 of 433 patients (75.1%) remaining in hospital on postoperative day 3 after surgery, 231 of 407 patients (56.8%) on day 5, 138 of 299 patients (46.2%) on day 8, and 70 of 111 patients (63.1%) on day 15. Gastrointestinal (47.4%), infectious (46.5%), pain-related (40.3%), pulmonary (39.4%), and renal problems (33.3%) were the most common forms of morbidity. CONCLUSION: The POMS is a reliable and valid survey of short-term postoperative morbidity in major elective surgery. Many patients remain in hospital without any morbidity as recorded by the POMS

Surgical Determinants of Patient-Reported Outcomes following Postmastectomy Reconstruction in Women with Breast Cancer.

This national prospective cohort study compared the patient-reported outcomes of breast cancer patients undergoing postmastectomy autologous reconstruction to those who had breast implants, in terms of aesthetic appearance; levels of psychological, physical, and sexual well-being; and overall satisfaction. Of 5063 women who underwent immediate reconstruction (n = 3349) or delayed reconstruction (n = 1714) between January 1, 2008, and March 31, 2009, in England, 2923 women who gave informed consent were sent validated, procedure-specific, 18-month follow-up questionnaires. Outcome scale scores ranged from 0 (poor) to 100 (excellent); multiple linear regression was used to adjust scores for patient and treatment characteristics. Two thousand two hundred eighty-nine women (78 percent) returned completed questionnaires (immediate reconstruction, n = 1528; delayed reconstruction, n = 761). For immediate reconstruction, mean overall satisfaction scores for the various techniques ranged from 67 to 85 (median, 67 to 93). For delayed reconstruction, mean overall satisfaction scores ranged from 70 to 85 (median, 75 to 100). For both groups, similar gradients were observed for the other outcome scales across techniques. Reconstruction using patients' own tissues tended to have higher mean adjusted scores compared with those techniques using implants alone (p < 0.0001 for aesthetic appearance, psychological well-being, sexual well-being, and satisfaction with outcomes for immediate and delayed reconstruction groups). Women who underwent autologous reconstruction tended to report greater satisfaction than those who underwent implant reconstruction. These results can inform patients of the anticipated outcomes of their selected surgery, but further research is required to confirm whether autologous reconstruction is superior in general. Therapeutic, II

Sharp upturn of life expectancy in the Netherlands: effect of more health care for the elderly?

During the 1980s and 1990s life expectancy at birth has risen only slowly in the Netherlands. In 2002, however, the rise in life expectancy suddenly accelerated. We studied the possible causes of this remarkable development. Mortality data by age, gender and cause of death were analyzed using life table methods and age-period-cohort modeling. Trends in determinants of mortality (including health care delivery) were compared with trends in mortality. Two-thirds of the increase in life expectancy at birth since 2002 were due to declines in mortality among those aged 65 and over. Declines in mortality reflected a period rather than a cohort effect, and were seen for a wide range of causes of death. Favorable changes in mortality determinants coinciding with the acceleration of mortality decline were mainly seen within the health care system. Health care expenditure rose rapidly after 2001, and was accompanied by a sharp rise of specialist visits, drug prescriptions, hospital admissions and surgical procedures among the elderly. A decline of deaths following non-treatment decisions suggests a change towards more active treatment of elderly patients. Our findings are consistent with the idea that the sharp upturn of life expectancy in the Netherlands was at least partly due to a sharp increase in health care for the elderly, and has been facilitated by a relaxation of budgetary constraints in the health care system

Development, Problem Behavior, and Quality of Life in a Population Based Sample of Eight-Year-Old Children with Down Syndrome

OBJECTIVE: Children with Down syndrome (DS) have delayed psychomotor development. We investigated levels of development, problem behavior, and Health-Related Quality of Life (HRQoL) in a population sample of Dutch eight-year-old children with DS. Developmental outcomes were compared with normative data of eight-year-old children from the general population. METHOD: Over a three-year-period all parents with an eight-year-old child with DS were approached by the national parent organization. Developmental skills were assessed by means of the McCarthy Scales of Children's Ability. To measure emotional and behavioral problems we used the Child Behavior Checklist. HRQoL was assessed with the TNO-AZL Children's Quality of Life questionnaire. Analyses of variance were applied to compare groups. RESULTS: A total of 337 children participated. Mean developmental age was substantially lower than mean calendar age (3.9 years, SD 0.87 and 8.1 years, SD 0.15 respectively). Mean developmental age was significantly lower among boys than girls (3.6 (SD 0.85) and 4.2 years (SD 0.82) respectively; p<0.001). Compared with the general population, children with DS had more emotional and behavioral problems (p<0.001). However on the anxious/depressed scale, they scored significantly more favorably (p<0.001). Significantly lower HRQoL scores for the scales gross motor skills, autonomy, social functioning and cognitive functioning were found (p-values<0.001). Hardly any differences were observed for the scales physical complaints, positive and negative emotions. CONCLUSION: Eight-year-old children with DS have an average developmental delay of four years, more often have emotional and behavioral problems, and have a less favorable HRQoL compared with children from the general population

Establishing Zebrafish as a Novel Exercise Model: Swimming Economy, Swimming-Enhanced Growth and Muscle Growth Marker Gene Expression

Zebrafish has been largely accepted as a vertebrate multidisciplinary model but its usefulness as a model for exercise physiology has been hampered by the scarce knowledge on its swimming economy, optimal swimming speeds and cost of transport. Therefore, we have performed individual and group-wise swimming experiments to quantify swimming economy and to demonstrate the exercise effects on growth in adult zebrafish

Early transcriptional response in the jejunum of germ-free piglets after oral infection with virulent rotavirus

Germ-free piglets were orally infected with virulent rotavirus to collect jejunal mucosal scrapings at 12 and 18 hours post infection (two piglets per time point). IFN-gamma mRNA expression was stimulated in the mucosa of all four infected piglets, indicating that they all responded to the rotavirus infection. RNA pools prepared from two infected piglets were used to compare whole mucosal gene expression at 12 and 18 hpi to expression in uninfected germ-free piglets (n = 3) using a porcine intestinal cDNA microarray. Microarray analysis identified 13 down-regulated and 17 up-regulated genes. Northern blot analysis of a selected group of genes confirmed the data of the microarray. Genes were functionally clustered in interferon-regulated genes, proliferation/differentiation genes, apoptosis genes, cytoskeleton genes, signal transduction genes, and enterocyte digestive, absorptive, and transport genes. Down-regulation of the transport gene cluster reflected in part the loss of rotavirus-infected enterocytes from the villous tips. Data mining suggested that several genes were regulated in lower- or mid-villus immature enterocytes and goblet cells, probably to support repair of the damaged epithelial cell layer at the villous tips. Furthermore, up-regulation was observed for IFN-γ induced guanylate binding protein 2, a protein that effectively inhibited VSV and EMCV replication in vitro (Arch Virol 150:1213–1220, 2005). This protein may play a role in the small intestine’s innate defense against enteric viruses like rotavirus

Structural basis for delta cell paracrine regulation in pancreatic islets

International audienceLittle is known about the role of islet delta cells in regulating blood glucose homeostasis in vivo. Delta cells are important paracrine regulators of beta cell and alpha cell secretory activity, however the structural basis underlying this regulation has yet to be determined. Most delta cells are elongated and have a well-defined cell soma and a filopodia-like structure. Using in vivo optogenetics and high-speed Ca2+ imaging, we show that these filopodia are dynamic structures that contain a secretory machinery, enabling the delta cell to reach a large number of beta cells within the islet. This provides for efficient regulation of beta cell activity and is modulated by endogenous IGF-1/VEGF-A signaling. In pre-diabetes, delta cells undergo morphological changes that may be a compensation to maintain paracrine regulation of the beta cell. Our data provides an integrated picture of how delta cells can modulate beta cell activity under physiological conditions

Viral epidemics in a cell culture: novel high resolution data and their interpretation by a percolation theory based model

Because of its relevance to everyday life, the spreading of viral infections has been of central interest in a variety of scientific communities involved in fighting, preventing and theoretically interpreting epidemic processes. Recent large scale observations have resulted in major discoveries concerning the overall features of the spreading process in systems with highly mobile susceptible units, but virtually no data are available about observations of infection spreading for a very large number of immobile units. Here we present the first detailed quantitative documentation of percolation-type viral epidemics in a highly reproducible in vitro system consisting of tens of thousands of virtually motionless cells. We use a confluent astroglial monolayer in a Petri dish and induce productive infection in a limited number of cells with a genetically modified herpesvirus strain. This approach allows extreme high resolution tracking of the spatio-temporal development of the epidemic. We show that a simple model is capable of reproducing the basic features of our observations, i.e., the observed behaviour is likely to be applicable to many different kinds of systems. Statistical physics inspired approaches to our data, such as fractal dimension of the infected clusters as well as their size distribution, seem to fit into a percolation theory based interpretation. We suggest that our observations may be used to model epidemics in more complex systems, which are difficult to study in isolation.Comment: To appear in PLoS ONE. Supporting material can be downloaded from http://amur.elte.hu/BDGVirus

Heterozygous Mutations of FREM1 Are Associated with an Increased Risk of Isolated Metopic Craniosynostosis in Humans and Mice

The premature fusion of the paired frontal bones results in metopic craniosynostosis (MC) and gives rise to the clinical phenotype of trigonocephaly. Deletions of chromosome 9p22.3 are well described as a cause of MC with variably penetrant midface hypoplasia. In order to identify the gene responsible for the trigonocephaly component of the 9p22.3 syndrome, a cohort of 109 patients were assessed by high-resolution arrays and MLPA for copy number variations (CNVs) involving 9p22. Five CNVs involving FREM1, all of which were de novo variants, were identified by array-based analyses. The remaining 104 patients with MC were then subjected to targeted FREM1 gene re-sequencing, which identified 3 further mutant alleles, one of which was de novo. Consistent with a pathogenic role, mouse Frem1 mRNA and protein expression was demonstrated in the metopic suture as well as in the pericranium and dura mater. Micro-computed tomography based analyses of the mouse posterior frontal (PF) suture, the human metopic suture equivalent, revealed advanced fusion in all mice homozygous for either of two different Frem1 mutant alleles, while heterozygotes exhibited variably penetrant PF suture anomalies. Gene dosage-related penetrance of midfacial hypoplasia was also evident in the Frem1 mutants. These data suggest that CNVs and mutations involving FREM1 can be identified in a significant percentage of people with MC with or without midface hypoplasia. Furthermore, we present Frem1 mutant mice as the first bona fide mouse model of human metopic craniosynostosis and a new model for midfacial hypoplasia

Utilising a systematic review-based approach to create a database of individual participant data for meta- and network meta-analyses: the RELEASE database of aphasia after stroke

Background: Collation of aphasia research data across settings, countries and study designs using big data principles will support analyses across different language modalities, levels of impairment, and therapy interventions in this heterogeneous population. Big data approaches in aphasia research may support vital analyses, which are unachievable within individual trial datasets. However, we lack insight into the requirements for a systematically created database, the feasibility and challenges and potential utility of the type of data collated. Aim: To report the development, preparation and establishment of an internationally agreed aphasia after stroke research database of individual participant data (IPD) to facilitate planned aphasia research analyses. Methods: Data were collated by systematically identifying existing, eligible studies in any language (≥10 IPD, data on time since stroke, and language performance) and included sourcing from relevant aphasia research networks. We invited electronic contributions and also extracted IPD from the public domain. Data were assessed for completeness, validity of value-ranges within variables, and described according to pre-defined categories of demographic data, therapy descriptions, and language domain measurements. We cleaned, clarified, imputed and standardised relevant data in collaboration with the original study investigators. We presented participant, language, stroke, and therapy data characteristics of the final database using summary statistics. Results: From 5256 screened records, 698 datasets were potentially eligible for inclusion; 174 datasets (5928 IPD) from 28 countries were included, 47/174 RCT datasets (1778 IPD) and 91/174 (2834 IPD) included a speech and language therapy (SLT) intervention. Participants’ median age was 63 years (interquartile range [53, 72]), 3407 (61.4%) were male and median recruitment time was 321 days (IQR 30, 1156) after stroke. IPD were available for aphasia severity or ability overall (n = 2699; 80 datasets), naming (n = 2886; 75 datasets), auditory comprehension (n = 2750; 71 datasets), functional communication (n = 1591; 29 datasets), reading (n = 770; 12 datasets) and writing (n = 724; 13 datasets). Information on SLT interventions were described by theoretical approach, therapy target, mode of delivery, setting and provider. Therapy regimen was described according to intensity (1882 IPD; 60 datasets), frequency (2057 IPD; 66 datasets), duration (1960 IPD; 64 datasets) and dosage (1978 IPD; 62 datasets). Discussion: Our international IPD archive demonstrates the application of big data principles in the context of aphasia research; our rigorous methodology for data acquisition and cleaning can serve as a template for the establishment of similar databases in other research areas