Difficult-to-heal wounds of mixed arterial/venous and venous etiology: A cost-effectiveness analysis of extracellular matrix

Importance: Difficult-to-heal wounds pose clinical and economic challenges, and cost-effective treatment options are needed. Objective: The aim of this study is to determine the cost-effectiveness of extracellular matrix (ECM) relative to standard of care (SC) on wound closure for the treatment of mixed arterial/venous (A/V) or venous leg ulcers (VLUs). Design, setting, and participants: A two-stage Markov model was used to predict the expected costs and outcomes of wound closure for ECM and SC. Outcome data used in the analysis were taken from an 8-week randomized clinical trial that directly compared ECM and SC. Patients were followed up for an additional 6 months to assess wound closure. Forty-eight patients completed the study; 25 for ECM and 23 for SC. SC was defined as a standard moist wound dressing. Transition probabilities for the Markov states were estimated from the clinical trial. Main outcomes and measures: The economic outcome of interest was direct cost per closed-wound week. Resource utilization was based on the treatment regimen used in the clinical trial. Costs were derived from standard cost references. The payer’s perspective was taken. Results: ECM-treated wounds closed, on average, after 5.4 weeks of treatment, compared with 8.3 weeks for SC wounds (P=0.02). Furthermore, complete wound closure was significantly higher in patients treated with ECM (P<0.05), with 20 wounds closed in the ECM group (80%) and 15 wounds closed in the SC group (65%). After 8 months, patients treated with ECM had substantially higher closed-wound weeks compared with SC (26.0 weeks versus 22.0 weeks, respectively). Expected direct costs per patient were $2, 527 for ECM and$2, 540 for SC (a cost savings of $13). Conclusion and relevance: ECM yielded better clinical outcomes at a slightly lower cost in patients with mixed A/V and VLUs. ECM is an effective treatment for wound healing and should be considered for use in the management of mixed A/V and VLUs

Oedema and fatty degeneration of the soleus and gastrocnemius muscles on MR images in patients with achilles tendon abnormalities

Objective: The purpose of this study was to evaluate the frequency of oedema and fatty degeneration of the soleus and gastrocnemius muscles in patients with Achilles tendon abnormalities. Methods: Forty-five consecutive patients (mean 51years; range 14-84years) with achillodynia were examined with magnetic resonance (MR) images of the calf. The frequency of oedema and fatty degeneration in the soleus and gastrocnemius muscles was determined in patients with normal tendons, tendinopathy and in patients with a partial tear or a complete tear of the Achilles tendon. Results: Oedema was encountered in 35% (7/20) of the patients with tendinopathy (n = 20; range 13-81years), and in 47% (9/19) of the patients with partial tears or complete tears (n = 19; 28-78years). Fatty degeneration was encountered in 10% (2/20) of the patients with tendinopathy, and in 32% (6/19) of the patients with tears. The prevalence of fatty degeneration was significantly more common in patients with a partial or complete tear compared with the patients with a normal Achilles tendon (p = 0.032 and p = 0.021, respectively). Conclusion: Oedema and fatty degeneration of the soleus and gastrocnemius muscles are common in patients with Achilles tendon abnormalitie

Genetically engineered minipigs model the major clinical features of human neurofibromatosis type 1.

Neurofibromatosis Type 1 (NF1) is a genetic disease caused by mutations in Neurofibromin 1 (NF1). NF1 patients present with a variety of clinical manifestations and are predisposed to cancer development. Many NF1 animal models have been developed, yet none display the spectrum of disease seen in patients and the translational impact of these models has been limited. We describe a minipig model that exhibits clinical hallmarks of NF1, including café au lait macules, neurofibromas, and optic pathway glioma. Spontaneous loss of heterozygosity is observed in this model, a phenomenon also described in NF1 patients. Oral administration of a mitogen-activated protein kinase/extracellular signal-regulated kinase inhibitor suppresses Ras signaling. To our knowledge, this model provides an unprecedented opportunity to study the complex biology and natural history of NF1 and could prove indispensable for development of imaging methods, biomarkers, and evaluation of safety and efficacy of NF1-targeted therapies

EIN ALTKROATISCHES GRABERFELD AUF DEM BERGE SPAS BEI KNIN

Autor objavljuje rezultate istraživanja starohrvatske nekropole na brdu Spasu kod Knina (otkriveno ukupno 228 grobova). Na temelju prikupljenih podataka tijekom višegodišnjih arheoloških istraživanja i sprovedene analize grobne arhitekture, pogrebnih običaja i grobnih nalaza utvrđeno je vrijeme ukopavanja na toj nekropoli i uputilo na mogući prostorni smještaj naselja kojemu je to groblje pripadalo. Završna razmatranja objelodanjenih grobnih nalaza otkrivaju niz novih spoznaja o gospoda.stvenim mogućnostima stanovništva, njihov kulturni i duhovni život u 9, 10. i 11. stoljeću. Osim starohrvatskih grobova na Spasu su otkopani i temeljni ostaci arhitekture, za koje se utvrdilo da pripadaju rimskom naselju, vjerojatno ostacima stare Ninie, odnosno Curcuma. Sve to popraćeno je obilnom dokumentacijskom građom i katalogom grobova.Westlich der Stadt Knin erstreckt sich der Berg Spas. Auf seinem siidlichen Teil erhebt sich die mittelalterliche Festung Knin, und an den nord lichen Teil schlieBt sich das Hochplateau des Berges Spas an, das im horizontalen Querschnitt cinE\u27 birnentormige Form hat. Spas ist anfangs des 18. lahrhunderts durch einen kiinstlichen Durchstich von der Festung getrennt worden. Im nordlichen, breitesten Teil des Plateaus wurde ein altkroatisches Graberfeld entdeckt, mit insgesamt 228 Grabern. Das erforsci1te Gebiet umfaBt etwa 1200 m2 Oberflache. Es wurden neben Grabern auch Fundamente von Bauwerken aus vorktoatischer Zeit gefunden, was bezeugt, daB es sich hier um eine komplexe archaologische Fundstatte handelt. Im ersten Teil seiner Abhandlung beschreibt. der Verfasser die Lage des Fundortes, seine strategische Bedeutung, und den geschichtlichen Ablauf der Forschungen an diesem Ort. AuBerdem erwahnt er unter anderen bedeutenden Funden auch die Entdeckung von Fundamenten von Bauwerken , fUr die er aufgrund von Fragmenten steinernen Skulpturen, Ziegeln und Fragmenten von KeramikgefaBen festelIen konnte, daB sie einer romisehen Ansiedlung angehorten. Durch Suchgrabung wurde festgestelIt, daB die Reste dieser Bauwerke sich auch auf den iibrigen Teil des Plateaus erstrecken, der bis jetzt nicht erforscht worden ist. Diese Entdeckungen, zusammen mit einem groBen, schon friiher untersuchten Graberfeld am ostlichen FuBe dieses Berges, genannt »Greblje«, sind ein starkes Argumentfi.ir die Annahme jener Forscher, die der Meinung sind, daB die alte, antike Stadtsiedlung Ninia, die von der Schriftstellern der Antike erwahnt wird , sich an der SteIle der heutigen Stadt Knin befunden hatte, beziehungsweise an der Stelle ihrer Festung und der Wallburg Spas. Im siidostlichen Teil des ausgegrabenen Graberfeldes hat man ziemlich groBe Schuttablagerungen gefunden, unter denen sich auch Stiicke von Mortel mit Farbresten befanden. An dieser Stelle und in ihrer unmittelbaren Nahe wurden einige steinerne Fragmente mit vorromanischer F1echtwerkplastik gefunden , die zu Kircheneinrichtungsgegenstanden aus dem 9. oder 10. lh. gehorten. Die erwahnten Funde weisen mjt Sicherheit darauf hin, daB sich an eben dieser Stelle, wo man den Schutt gefunden hat, eine altkroatische Kirche befunden hatte, der die gefundenen Fragmente angehorten. Da sich von diesem Kirchenbau auch nicht der allergeringste Rest einer Mauer erhalten hat, kann man nur schlieBen, daB die Kirche bis zu den Grundmauern zerstort worden war, und daB ihre Steine als Baurnaterial fUr die Mauern der nahegelegenen Festung verwendet wurden. Der zwei te Teil dieser Abhandlung enthalt den Katalog der Grabarchitektur und ihres lnventars. Hier findet man kurz gefaBt die wichtigsten Angaben i.iber jedes cinzeIne Grab und die osteologischen Funde, sowie eine genaue Beschreibung der Grabbeigaben. Der dritte Teil behandelt die allgemeinen Merkmale des Graberfeldes. Wegen der ungi.instigen Bodenstruktur, sowie der Fundamente der Bauwerke, besitzt das Graberfeld nicht die Merkmale von Reihengrabern, Die Graber sind sehr verschiedenartig orientiert, und liegen in allen Richtungen; der groBte Teil der Graber war trotzdem richtjg orientiert, in der Richtung Osten-Westen (103 Graber) . In den meisten Grabern befand sich nur ein Verstorbener, manchmal jedoch auch mehrere. Die gefundenen osteologischen Reste bestatigen, daB das Graberfeld einer Siedlung zugehorig; mit einer gleich groBen Anzahl von bestatteten Mannern , Frauern und Kindern. Die Graber waren meistens aus behauener Rauhwacke , aus unregelmaBigen Steinplatten oder aus Bruchsteinen gebaut. Die behauene Rauhwacke ftir die Graber stammte wahrscheinlich von den eingesttirzten Bauwerken in der nahen Umgebung. Weiterhin analysiert der Verfasser die Grabfunde, meistens Schmuck, und zwar Ohrringe und Ringe. Indem er die typologischen Besonderheiten der einzelnen Gegenstande genau beurteilt, und sie mit analogem Material aus den tibrigen altkroatischen und anderen Graberfeldern vergleicht, kommt er zu Schltissen ber die Herkunft und\u27 Datierung der Funde. Mehr Aufmerksamkeit schenkt der Verfasser den Ohrringen vom Typ mit drei Beeren und zwar deshalb, weil in letzter Zeit versucht wurde, fast alle entwickelteren Varianten dieses Typs, die in Grabern auf dem Gebiet des altkroatisches Staates gefunden worden waren, von allen tibrigen Ohrringen die ebenfalls auf diesem Gebiet gefunden wurden, zu trennen. [ndem er auf das Problem der Datierung und Herkunft der Ohrringe mit drei Beeren eingeht, versuchte der Verfasser aufgrund einer Reihe sicherer Tatsachen und Hinweise darauf hinzuweisen, daB dieser Typ von Ohrringen, beziehungsweise die starker entwickelten Varianten , nicht von den tibrigen Typenvarianten altkroatischer Ohrringe isoliert werden dtirfen, die auf dem Gebiet des dalmatinischen Kroatiens gefunden worden waren , und die meistens in die Zeit vom Beginn des 9. bis zum Ende des 11. lahrhunderts datiert werden. Er machte ebenfalls darauf aufmerksam, daB samtliche Typen von altkroatischen Ohrringen, und so auch die entwickelteren Varianten von Ohrringen mit drei Beeren, die aus Grabern des Mutterlandes stammen, aus einheimischen Goldschmiedewerkstatten stammen , und daB sie als Ganzes eine altkroatische Kulturgruppe bilden. AuBer seinen Vermutungen tiber die Lage und GroBe der Ansiedlung, zu der das Graberfeld auf dem Berge Spas gehorte, ist der Verfasser im Ganzen der Meinun~, daB das Graberfeld auf Spas dem Zeitraum des frtihfeudalen kroatischen Staates angehorte, d. h., daB das Graberfeld sei t dem Anfang des 9. Jahrhunderts bestanden hatte und kontinuierlich bis zum Ende des ll. Jahrhunderts fortdauerte

Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque

Carotid intima media thickness (cIMT) and plaque determined by ultrasonography are established measures of subclinical atherosclerosis that each predicts future cardiovascular disease events. We conducted a meta-analysis of genome-wide association data in 31,211 participants of European ancestry from nine large studies in the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. We then sought additional evidence to support our findings among 11,273 individuals using data from seven additional studies. In the combined meta-analysis, we identified three genomic regions associated with common carotid intima media thickness and two different regions associated with the presence of carotid plaque (P < 5 × 10 -8). The associated SNPs mapped in or near genes related to cellular signaling, lipid metabolism and blood pressure homeostasis, and two of the regions were associated with coronary artery disease (P < 0.006) in the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis (CARDIoGRAM) consortium. Our findings may provide new insight into pathways leading to subclinical atherosclerosis and subsequent cardiovascular events

Support for UNRWA's survival

The United Nations Relief and Works Agency for Palestine Refugees in the Near East (UNRWA) provides life-saving humanitarian aid for 5·4 million Palestine refugees now entering their eighth decade of statelessness and conflict. About a third of Palestine refugees still live in 58 recognised camps. UNRWA operates 702 schools and 144 health centres, some of which are affected by the ongoing humanitarian disasters in Syria and the Gaza Strip. It has dramatically reduced the prevalence of infectious diseases, mortality, and illiteracy. Its social services include rebuilding infrastructure and homes that have been destroyed by conflict and providing cash assistance and micro-finance loans for Palestinians whose rights are curtailed and who are denied the right of return to their homeland

Problem and Pathological Gambling in a Sample of Casino Patrons

Relatively few studies have examined gambling problems among individuals in a casino setting. The current study sought to examine the prevalence of gambling problems among a sample of casino patrons and examine alcohol and tobacco use, health status, and quality of life by gambling problem status. To these ends, 176 casino patrons were recruited by going to a Southern California casino and requesting that they complete an anonymous survey. Results indicated the following lifetime rates for at-risk, problem, and pathological gambling: 29.2, 10.7, and 29.8%. Differences were found with regards to gambling behavior, and results indicated higher rates of smoking among individuals with gambling problems, but not higher rates of alcohol use. Self-rated quality of life was lower among pathological gamblers relative to non-problem gamblers, but did not differ from at-risk or problem gamblers. Although subject to some limitations, our data support the notion of higher frequency of gambling problems among casino patrons and may suggest the need for increased interventions for gambling problems on-site at casinos

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Large-scale gene-centric analysis identifies novel variants for coronary artery disease

Coronary artery disease (CAD) has a significant genetic contribution that is incompletely characterized. To complement genome-wide association (GWA) studies, we conducted a large and systematic candidate gene study of CAD susceptibility, including analysis of many uncommon and functional variants. We examined 49,094 genetic variants in ~2,100 genes of cardiovascular relevance, using a customised gene array in 15,596 CAD cases and 34,992 controls (11,202 cases and 30,733 controls of European descent; 4,394 cases and 4,259 controls of South Asian origin). We attempted to replicate putative novel associations in an additional 17,121 CAD cases and 40,473 controls. Potential mechanisms through which the novel variants could affect CAD risk were explored through association tests with vascular risk factors and gene expression. We confirmed associations of several previously known CAD susceptibility loci (eg, 9p21.3:p&lt;10-33; LPA:p&lt;10-19; 1p13.3:p&lt;10-17) as well as three recently discovered loci (COL4A1/COL4A2, ZC3HC1, CYP17A1:p&lt;5×10-7). However, we found essentially null results for most previously suggested CAD candidate genes. In our replication study of 24 promising common variants, we identified novel associations of variants in or near LIPA, IL5, TRIB1, and ABCG5/ABCG8, with per-allele odds ratios for CAD risk with each of the novel variants ranging from 1.06-1.09. Associations with variants at LIPA, TRIB1, and ABCG5/ABCG8 were supported by gene expression data or effects on lipid levels. Apart from the previously reported variants in LPA, none of the other ~4,500 low frequency and functional variants showed a strong effect. Associations in South Asians did not differ appreciably from those in Europeans, except for 9p21.3 (per-allele odds ratio: 1.14 versus 1.27 respectively; P for heterogeneity = 0.003). This large-scale gene-centric analysis has identified several novel genes for CAD that relate to diverse biochemical and cellular functions and clarified the literature with regard to many previously suggested genes.</p