Bleeding-related hospitalization in patients with von Willebrand disease and the impact of prophylaxis: Results from national registers in Sweden compared with normal controls and participants in the von Willebrand Disease Prophylaxis Network.

INTRODUCTION: Patients suffering from von Willebrand disease (VWD) have a variety of bleeding symptoms and require both outpatient care for treatment and, in more severe cases, hospitalization. AIM: To investigate the impact of having VWD on frequency of hospitalization compared to a control group and to evaluate whether regular replacement therapy (prophylaxis) is associated with reduction in the number of hospitalizations. METHODS: Linkage of national population-based registries was used in the Congenital Bleeding Disorders study in Sweden (CBDS). Data were from the von Willebrand Disease Prophylaxis Network (VWD PN). RESULTS: The national registries contained 2790 subjects with a diagnosis of VWD between 1987 and 2009. A total of 13 920 age- and gender-matched controls were identified. There were 2.0 times (range 1.5-2.5) as many inpatient hospitalizations among subjects with VWD compared to controls. The most common causes of hospitalization were gastrointestinal (GI) bleeding (n = 232 as primary diagnosis), menorrhagia (n = 198) and epistaxis (n = 192). Outpatient visits per year were also twice as common among those with VWD. From the VWD PN, 105 subjects were included (VWD type 3, 52.4%; type2A, 22.9%; type 1, 12.4% and other types, 3.9%). A total of 122 hospitalizations due to bleeding episodes, dominated by GI bleeds, were analysed. Significantly fewer hospitalizations occurred after initiation of prophylaxis (75 prior to and 45 after, P = .006). CONCLUSION: Our study indicates that subjects with VWD have a considerably higher consumption of healthcare resources compared to controls and that initiation of prophylaxis may reduce the number of hospitalizations due to bleeding.

Efficacy of the Danish epilepsy surgery programme.

OBJECTIVE: Despite optimal medical treatment, approximately one-third of patients with epilepsy continue to have seizures. Epilepsy surgery is widely accepted as a therapeutic option in the selected subset of patients with drug-resistant focal epilepsy. Here, we report the results of the Danish epilepsy surgery programme from 2009 to 2014. MATERIAL AND METHODS: A total of 169 consecutive patients, operated at Rigshospitalet, were included. Information was gathered from digital patient records. Before 1-year follow-up, two patients were lost to follow-up and three were referred to new surgery. RESULTS: The median years of drug resistance before operation were 11 years. At 1-year follow-up (n = 164), seizure outcomes were as follows: 65% Engel I (free from disabling seizures), 51% Engel IA (completely seizure free) and 9% Engel IV (no worthwhile improvement), and for patients operated in the medial temporal lobe (n = 114): 70% Engel I, 56% Engel IA, 5% Engel IV. The outcomes of the 53 patients needing intracranial EEG recording (ICR) were not significantly different from the patients only evaluated with surface EEG. None of the eight MRI-negative patients operated outside the medial temporal lobe after ICR were free of disabling seizures. 12% of MTLE patients developed de novo depression after epilepsy surgery despite good surgical outcome. Three patients required rehabilitation due to post-operative hemiplegia. CONCLUSION: The outcomes of the Danish epilepsy surgery programme align with international results found in recent meta-analyses. Serious complications to epilepsy surgery are seldom. In accordance with international recommendations, Danish drug-resistant patients should be referred to epilepsy surgery evaluation at an earlier stage of the disease.

Place-based social contact and mixing: a typology of generic meeting places of relevance for infectious disease transmission.

This study aims to develop a typology of generic meeting places based on social contact and mixing of relevance for infectious disease transmission. Data were collected by means of a contact diary survey conducted on a representative sample of the Swedish population. The typology is derived from a cluster analysis accounting for four dimensions associated with transmission risk: visit propensity and its characteristics in terms of duration, number of other persons present and likelihood of physical contact. In the analysis, we also study demographic, socio-economic and geographical differences in the propensity of visiting meeting places. The typology identifies the family venue, the fixed activity site, the family vehicle, the trading plaza and the social network hub as generic meeting places. The meeting place typology represents a spatially explicit account of social contact and mixing relevant to infectious disease modelling, where the social context of the outbreak can be highlighted in light of the actual infectious disease.

Relevance of workplace social mixing during influenza pandemics: an experimental modelling study of workplace cultures.

Workplaces are one of the most important regular meeting places in society. The aim of this study was to use simulation experiments to examine the impact of different workplace cultures on influenza dissemination during pandemics. The impact is investigated by experiments with defined social-mixing patterns at workplaces using semi-virtual models based on authentic sociodemographic and geographical data from a North European community (population 136 000). A simulated pandemic outbreak was found to affect 33% of the total population in the community with the reference academic-creative workplace culture; virus transmission at the workplace accounted for 10·6% of the cases. A model with a prevailing industrial-administrative workplace culture generated 11% lower incidence than the reference model, while the model with a self-employed workplace culture (also corresponding to a hypothetical scenario with all workplaces closed) produced 20% fewer cases. The model representing an academic-creative workplace culture with restricted workplace interaction generated 12% lower cumulative incidence compared to the reference model. The results display important theoretical associations between workplace social-mixing cultures and community-level incidence rates during influenza pandemics. Social interaction patterns at workplaces should be taken into consideration when analysing virus transmission patterns during influenza pandemics.

Nationwide time trends and risk factors for in-hospital falls-related major injuries.

BACKGROUND: Accidental falls during hospitalisation have a range of complications and more information is needed to improve prevention. We investigated patterns of in-hospital fall-related major injuries in the period 2000-2012 and the association between chronic conditions and in-hospital fall-related major injuries. METHODS: Using administrative databases, patients aged 65+ years with in-hospital falls causing fractures or head injuries with need for surgery or intensive observation were identified as cases and were individually matched with five controls. Joinpoint regression was used to examine time trends and conditional logistic regression was used to analyse odds ratio (OR) for in-hospital falls-related major injuries according to a range of comorbidities. RESULTS: Four thousand seven hundred and fifty-four cases were identified from 2000 to 2012 and the most common injury was femur fracture (61.55%). For individuals aged 65-74 and 75+ years, the incidence of in-hospital falls-related major injuries per 100,000 hospital days increased significantly in 2000-2012 (average annual change: 3.2%, CI: 0.6-5.8) and 2007-2012 (average annual change: 11.4%, CI: 5.7-17.5), respectively. Significantly increased OR for in-hospital fall-related major injuries were found for individuals with dementia (OR = 2.34, CI: 1.87-2.92), osteoporosis (OR = 1.68, CI: 1.43-1.99), stroke (OR = 1.63, CI: 1.41-1.88), depression (OR = 1.24, CI: 1.09-1.41), chronic obstructive pulmonary disease (OR = 1.18, CI: 1.01-1.39) and Parkinson disease (OR = 1.17, CI: 1.01-1.34). CONCLUSIONS: In-hospital falls-related major injuries increased significantly during the study period. Elderly with dementia, osteoporosis, stroke, depression, chronic obstructive pulmonary disease and Parkinson disease were associated with increased OR for in-hospital fall-related major injuries. Increased focus on patients with these comorbidities is warranted to decrease the increasing incidence in in-hospital major injuries.

Predictive performance of telenursing complaints in influenza surveillance: a prospective cohort study in Sweden.

Syndromic data sources have been sought to improve the timely detection of increased influenza transmission. This study set out to examine the prospective performance of telenursing chief complaints in predicting influenza activity. Data from two influenza seasons (2007/08 and 2008/09) were collected in a Swedish county (population 427,000) to retrospectively determine which grouping of telenursing chief complaints had the largest correlation with influenza case rates. This grouping was prospectively evaluated in the three subsequent seasons. The best performing telenursing complaint grouping in the retrospective algorithm calibration was fever (child, adult) and syncope (r=0.66; p<0.001). In the prospective evaluation, the performance of 14-day predictions was acceptable for the part of the evaluation period including the 2009 influenza pandemic (area under the curve (AUC)=0.84; positive predictive value (PPV)=0.58), while it was strong (AUC=0.89; PPV=0.93) for the remaining evaluation period including only influenza winter seasons. We recommend the use of telenursing complaints for predicting winter influenza seasons. The method requires adjustments when used during pandemics.

Measurement of health-related quality of life in dermatological research and practice: outcome of the EADV Taskforce on Quality of Life.

In the last decade, the importance of the measurement of health-related quality of life (HRQoL) has grown significantly. Today, HRQoL measurement is generally considered to be important in clinical trials, in the assessment of disease severity, in patient management and in the field of health economics. Therefore, a good understanding of the concept of HRQoL and its measurement instruments is a prerequisite for both researchers and clinicians. The European Academy for Dermatology and Venereology (EADV) Taskforce on Quality of Life encourages the application of HRQoL instruments in research and clinical practice, and with this manuscript, the Taskforce aims to contribute to the quality of this application. In dermatology, a large number of HRQoL instruments exist and herewith, we summarize the most commonly used generic and dermatology-specific HRQoL instruments. Information is given on the most important psychometric characteristics of these instruments, including: scale structure, reliability, validity and responsiveness. Furthermore, a flow chart is provided to support researchers and clinicians in selecting an existing instrument or, in case an appropriate instrument does not exist, in finding alternative solutions. The present manuscript is the first of a series of manuscripts to be written on behalf of the EADV Taskforce on Quality of Life, aiming to contribute to the scientific knowledge and measurement of patient reported outcomes in dermatological research and practice.

Patient-Oriented SCORAD (PO-SCORAD): a new self-assessment scale in atopic dermatitis validated in Europe.

BACKGROUND: Patient-oriented medicine is an emerging concept, encouraged by the World Health Organization, to greater involvement of the patient in the management of chronic diseases. The Patient-Oriented SCORing Atopic Dermatitis (PO-SCORAD) index is a self-assessment score allowing the patient to comprehensively evaluate the actual course of atopic dermatitis (AD), using subjective and objective criteria derived mainly from the SCORAD, a validated AD severity clinical assessment tool. OBJECTIVES: To validate the PO-SCORAD index in a large European population of patients exhibiting all forms of AD severity by assessing its correlation with the SCORAD index. PATIENTS/METHODS: Four hundred and seventy-one patients (185 adults, 286 children) consulting for AD in hospitals from 9 European countries were recruited. The investigators and the patients used the SCORAD and PO-SCORAD scales, respectively, to assess AD severity at inclusion (D0) and 28 ± 7 days later (D28). RESULTS: Patient-Oriented SCORing Atopic Dermatitis and SCORAD scores were significantly correlated at D0 [r = 0.67 (95% CI: 0.62; 0.72), P < 0.0001]. Consistency was confirmed at D28, with a stronger linear correlation between both scales [r = 0.79 (95% CI: 0.75; 0.83), P < 0.0001]. Absolute changes from baseline in SCORAD and PO-SCORAD scores were also significantly correlated [r= 0.71 (95% CI: 0.64; 0.76), P < 0.0001]. Although no specific intervention was investigated, AD improved over the study, with a decrease of PO-SCORAD and SCORAD scores from D0 to D28 by -19.19% and -24.39%, respectively. The consistency of the correlations was similar in the adult and children groups. CONCLUSIONS: This study validated the use of PO-SCORAD to self-assess AD severity and demonstrated its good correlation with SCORAD.

Economic impact of biofouling on a naval surface ship.

In the present study, the overall economic impact of hull fouling on a mid-sized naval surface ship (Arleigh Burke-class destroyer DDG-51) has been analyzed. A range of costs associated with hull fouling was examined, including expenditures for fuel, hull coatings, hull coating application and removal, and hull cleaning. The results indicate that the primary cost associated with fouling is due to increased fuel consumption attributable to increased frictional drag. The costs related to hull cleaning and painting are much lower than the fuel costs. The overall cost associated with hull fouling for the Navy's present coating, cleaning, and fouling level is estimated to be $56M per year for the entire DDG-51 class or $1B over 15 years. The results of this study provide guidance as to the amount of money that can be reasonably spent for research, development, acquisition, and implementation of new technologies or management strategies to combat hull fouling.

Detailed molecular and clinical characterization of three patients with 21q deletions.

We have investigated three patients with 21q deletions, two with developmental delay, dysmorphic features and internal organ malformations, and one with cognitive function within the normal range but with some deficits in gross and fine motor development. All aberrations were characterized by array-comparative genomic hybridization (array-CGH). In addition, extensive fluorescence in situ hybridization (FISH) mapping on metaphase chromosomes and mechanically stretched chromosomes was performed on patient 1 who had an extremely complex intrachromosomal rearrangement with 16 breakpoints, four deletions and four duplications. Patients 2 and 3 had interstitial deletions comprising 21q21.1-21q22.11 and 21q11.2-21q21.3, respectively. Partial deletions of 21q are rare and these patients display a highly variable phenotype depending on the size and position of the deletion. A review of the literature identified 38 cases with pure 21q deletions. Twenty-three of these had reliable mapping data. The combined information of present and previous cases suggests that the ITSN1 gene is involved in severe mental retardation in patients with 21q deletion. In addition, a critical region of 0.56 Mb containing four genes, KCNE1, DSCR1, CLIC6 and RUNX1, is associated with severe congenital heart defects, and deletions of the most proximal 15-17 Mb of 21q is associated with mild or no cognitive impairment, but may lead to problems with balance and motor function.

Insights into the Pu isotopic composition (239Pu, 240Pu, and 241Pu) and 236U in marshland samples from Madagascar.

This work provides new insights into the presence of 239Pu, 240Pu, 241Pu, and 236U in the Southern Hemisphere through the study of peat bog cores from marshlands in Madagascar (19°S). 210Pb, 238Pu and 239+240Pu activities were characterized by alpha spectrometry in previous studies. Here, Pu from alpha-spectrometry discs corresponding to 10 peat-bog cores (85 samples) was reassessed for the aim of completing its isotopic composition (239Pu, 240Pu, and 241Pu) by Accelerator Mass Spectrometry. In addition, 236U was studied in a single core exhibiting unusually low 240Pu/239Pu ratios. Integrated 240Pu/239Pu atom ratios in the single cores ranged above and below the (0-30°S) fallout average ratio, 0.173 ± 0.027, from 0.126 ± 0.003 to 0.206 ± 0.002, without a regional pattern, thereby demonstrating the heterogeneous distribution of the 239Pu and 240Pu signal. However, such a variability was not observed for 241Pu/239Pu, ranging from (6 ± 1) · 10-4 to (11 ± 1) · 10-4 and consistently below the (0-30°S) fallout ratio of (9.7 ± 0.3) · 10-4 (2012). The integrated 236U/239Pu atom ratio in the studied core, 0.147 ± 0.005, was also significantly lower than the values reported for the global fallout in the Northern Hemisphere, in the 0.20-0.23 range. Our results point out to stratospheric fallout as the main source of both 236U and 241Pu at the studied site, whereas 239Pu and 240Pu signals show the influence of tropospheric fallout from the low-yield tests conducted in Australia (1952-1958) by United Kingdom and in French Polynesia (1966-1975) by France despite the long relative distances (i.e. about 15,000 and 8500 km). It was also demonstrated that a representative number of samples is necessary in order to assess Pu contamination and its various origins in a specific region in the Southern Hemisphere due to the heterogeneous distribution, and results based on single sample analysis should be interpreted with caution.

Pit lakes from Southern Sweden: natural radioactivity and elementary characterization.

Natural radioactivity in the environment is a field gaining more attention in last decades. This work is focused on the study of natural radioactivity complemented with elementary characterization at former non-uraniferous mining areas in Sweden. This aim is addressed through the study of mining lakes, called pit lakes, which are water bodies generated after opencast mining. Environmental matrices (water, sediments and rocks) from 32 Swedish pit lakes, commonly used for recreational purposes were radiometrically characterized via alpha (238U, 234U, 232Th, 230Th, 210Po isotopes) and gamma spectrometry (238U and 232Th series radionuclides). Additionally, ambient dose rate equivalent in the immediate surrounding of each pit lake was quantified. Physico-chemical parameters (pH, specific conductivity, dissolved oxygen, oxidation-reduction potential) and elemental composition (major and trace elements by ICP-MS) were analysed in water samples and elementary composition of sediments/rocks was measured by XRF and SEM-EDX in some specific cases. A non-negligible number of pit lakes (26%) with enhanced U levels in water was found. At some sites, rocks contained up to 4% of U in areas with high degree of interaction with local population. Concerning the elementary perspective, another popular site (due to its turquoise water) was found to have elevated dissolved heavy metal levels. Results obtained in this work prove that measurement of natural radioactivity is another component that should be included in routine analysis of characterization in mining areas, especially if restauration of post-mining sites is intended for human recreational.

226Ra, 210Po and lead isotopes in a pit lake water profile in Sweden.

A pit lake arises as a consequence of anthropogenic activities in opencast mining areas. These water bodies may be enriched in hazardous stable contaminants and/or in naturally occurring radionuclides depending on the local geological conditions. Mining legacy in Sweden produced hundreds of these pit lakes and most of them are used for recreational purposes in the southern part of the country. In this paper, one pit lake was selected for having enhanced levels of natural radionuclides. Physico-chemical parameters (temperature, pH, oxidation-reduction potential, dissolved oxygen and depth), elemental composition (via Inductive Coupled Plasma Mass Spectrometry) and radiometric characterization (via alpha spectrometry of 226Ra, 210Po and 210Pb) were carried along the depth of a 60 m depth pit lake, with the main aim to describe how natural radionuclides and elements behaves with depth in a non-uraniferous pit lake. Based on observed changes in physico-chemical parameters, a thermocline and a chemocline region were identified at around 10 and 30 m depth respectively. Concerning radionuclides, 226Ra ranged from 75 ± 3 up to 360 ± 12 mBq/kg while 210Po ranged from 11 ± 1 up to 71 ± 3 mBq/kg. 210Pb distribution with depth was also determined via secular equilibrium with 210Po after 2 years and also stable Pb was measured. Disequilibrium 226Ra-210Pb was found and the residence time of 210Pb in the water column was assessed. Additionally, different vertical distributions between 210Pb and Pb were found which points out different sources for different lead isotopes in the water body.

Barnacle reattachment: a tool for studying barnacle adhesion.

Standard approaches for measuring adhesion strength of fouling organisms use barnacles, tubeworms or oysters settled and grown in the field or laboratory, to a measurable size. These approaches suffer from the vagaries of larval supply, settlement behavior, predation, disturbance and environmental stress. Procedures for reattaching barnacles to experimental surfaces are reported. When procedures are followed, adhesion strength measurements on silicone substrata after 2 weeks are comparable to those obtained using standard methods. Hydrophilic surfaces require reattachment for 2-4 weeks. The adhesion strength of barnacles in reattachment assays was positively correlated to results obtained from field testing a series of experimental polysiloxane fouling-release coatings (r = 0.89). The reattachment method allows for precise barnacle orientation, enabling the use of small surfaces and the potential for automation. The method enables down-selection of coatings from combinatorial approaches to manageable levels for definitive field testing. Reattachment can be used with coatings that combine antifouling and fouling-release technologies.

A new Certified Reference Material for radionuclides in Irish sea sediment (IAEA-385).

A new Certified Reference Material (CRM) for radionuclides in sediment (IAEA-385) is described and the results of the certification process are presented. Eleven radionuclides ((40)K, (137)Cs, (226)Ra, (228)Ra, (230)Th, (232)Th, (234)U, (238)U, (238)Pu, (239+240)Pu and (241)Am) have been certified and information mass activities with 95% confidence intervals are given for seven other radionuclides ((90)Sr, (210)Pb((210)Po), (235)U, (239)Pu, (240)Pu and (241)Pu). Results for less frequently reported radionuclides ((60)Co, (99)Tc, (134)Cs, (155)Eu, (224)Ra and (239)Np) and information on some activity and mass ratios are also reported. The CRM can be used for quality assurance/quality control of the analysis of radionuclides in sediment samples, for the development and validation of analytical methods and for training purposes.

On the presence of plutonium in Madagascar following the SNAP-9A satellite failure.

This study examined the 238Pu and 239+240Pu activity concentration and the 240Pu/239Pu atomic ratio in peat bogs sampled in 2012 from marshlands in central Madagascar. The purpose was to investigate the presence of plutonium isotopes, 238, 239, 240Pu, from the 1964 satellite failure carrying a SNAP-9A radiothermal generator. With an average 238Pu/239+240Pu activity ratio of 0.165 ± 0.02 (decay corrected to 1964), the peat bogs in Madagascar exhibit similar values as the ones found in the southeastern African continent, except they are one order of magnitude higher than expected (0.025) from global fallout in the Southern Hemisphere. The 240Pu/239Pu atomic ratio showed a distinct decrease for layers dating back to the mid-1960s (down to 0.069 compared with an anticipated ratio of 0.17 for global fallout), indicating that the SNAP-9A failure also resulted in an elevated deposition of 239Pu. The obtained results demonstrate that further Pu analysis in Madagascar and in southeastern continental Africa is necessary to fully account for the regional Pu deposition from the SNAP-9A event.

Increased proportion of mature NK cells is associated with successful imatinib discontinuation in chronic myeloid leukemia.

Recent studies suggest that a proportion of chronic myeloid leukemia (CML) patients in deep molecular remission can discontinue the tyrosine kinase inhibitor (TKI) treatment without disease relapse. In this multi-center, prospective clinical trial (EURO-SKI, NCT01596114) we analyzed the function and phenotype of T and NK cells and their relation to successful TKI cessation. Lymphocyte subclasses were measured from 100 imatinib-treated patients at baseline and 1 month after the discontinuation, and functional characterization of NK and T cells was done from 45 patients. The proportion of NK cells was associated with the molecular relapse-free survival as patients with higher than median NK-cell percentage at the time of drug discontinuation had better probability to stay in remission. Similar association was not found with T or B cells or their subsets. In non-relapsing patients the NK-cell phenotype was mature, whereas patients with more naïve CD56bright NK cells had decreased relapse-free survival. In addition, the TNF-α/IFN-γ cytokine secretion by NK cells correlated with the successful drug discontinuation. Our results highlight the role of NK cells in sustaining remission and strengthen the status of CML as an immunogenic tumor warranting novel clinical trials with immunomodulating agents.

ESPEN Guidelines on Enteral Nutrition: Liver disease.

Enteral nutrition (EN) by means of oral nutritional supplements (ONS) and tube feeding (TF) offers the possibility to increase or to insure nutrient intake in case of insufficient oral food intake. The present guideline is intended to give evidence-based recommendations for the use of ONS and TF in patients with liver disease (LD). It was developed by an interdisciplinary expert group in accordance with officially accepted standards and is based on all relevant publications since 1985. The guideline was discussed and accepted in a consensus conference. EN by means of ONS is recommended for patients with chronic LD in whom undernutrition is very common. ONS improve nutritional status and survival in severely malnourished patients with alcoholic hepatitis. In patients with cirrhosis, TF improves nutritional status and liver function, reduces the rate of complications and prolongs survival. TF commenced early after liver transplantation can reduce complication rate and cost and is preferable to parenteral nutrition. In acute liver failure TF is feasible and used in the majority of patients.

Certified reference material for radionuclides in fish flesh sample IAEA-414 (mixed fish from the Irish Sea and North Sea).

A certified reference material (CRM) for radionuclides in fish sample IAEA-414 (mixed fish from the Irish Sea and North Seas) is described and the results of the certification process are presented. Nine radionuclides (40K, 137Cs, 232Th, 234U, 235U, 238U, 238Pu, 239+240Pu and 241Am) were certified for this material. Information on massic activities with 95% confidence intervals is given for six other radionuclides (90Sr, 210Pb(210Po), 226Ra, 239Pu, 240Pu 241Pu). Less frequently reported radionuclides (99Tc, 129I, 228Th, 230Th and 237Np) and information on some activity and mass ratios are also included. The CRM can be used for quality assurance/quality control of the analysis of radionuclides in fish sample, for the development and validation of analytical methods and for training purposes. The material is available from IAEA, Vienna, in 100 g units.