Replacing the Z-phenyl Ring in Tamoxifen® with a para-Connected NCN Pincer-Pt-Cl Grouping by Post-Modification

Post-modification of a series of NCN-pincer platinum(II) complexes [PtX(NCN-R-4)] (NCN = [C6H2(CH2NMe2)2-2,6]–, R = C(O)H, C(O)Me and C(O)Et), X = Cl– or Br–) at the para-position using the McMurry reaction was studied. The synthetic route towards two new [PtCl(NCN-R-4)] (R = C(O)Me and C(O)Et) complexes used above is likewise described. The utility and limitations of the McMurry reaction involving these pincer complexes was systematically evaluated. The predicted “homo-coupling” reaction of [PtBr(NCN-C(O)H-4)] led to the unexpected formation of 3,3′,5,5′-tetra[(dimethylamino)methyl]-4,4′-bis(platinum halide)-benzophenone (halide = Br or Cl), referred to hereafter as the bispincer-benzophenone complex 13. This material was further characterized using X-ray crystal structure determination. The applicability of the pincer complexes in the McMurry reaction is shown to open a route towards the synthesis of tamoxifen-type derivatives of which one phenyl ring of Tamoxifen® itself is replaced by an NCN arylplatinum pincer fragment. The newly synthesized derivatives can be used as potential candidates in anti-cancer drug screening protocols. Two NCN-arylpincer platinum tamoxifen type derivatives, 5 and 6, were successfully synthesized and of 5 the separation of the diastereomeric E-/Z-forms was achieved. Compound 6, which is the pivaloyl protected NCN pincer platinum hydroxy-Tamoxifen® derivative, was obtained as a mixture of E-/Z-isomers. The new derivatives were further analyzed and characterized with 1H-, 13C{1H}- and 195Pt{1H}-NMR, IR, exact mass MS and elemental analysis.This research was partly funded by the Council for Chemical Sciences of the Netherlands Organization for Scientific Research (NWO/CW) G.D.B., M.L

Towards an International Classification for Patient Safety: the conceptual framework

Global advances in patient safety have been hampered by the lack of a uniform classification of patient safety concepts. This is a significant barrier to developing strategies to reduce risk, performing evidence-based research and evaluating existing healthcare policies relevant to patient safety. Since 2005, the World Health Organization's World Alliance for Patient Safety has undertaken the Project to Develop an International Classification for Patient Safety (ICPS) to devise a classification which transforms patient safety information collected from disparate systems into a common format to facilitate aggregation, analysis and learning across disciplines, borders and time. A drafting group, comprised of experts from the fields of patient safety, classification theory, health informatics, consumer/patient advocacy, law and medicine, identified and defined key patient safety concepts and developed an internationally agreed conceptual framework for the ICPS based upon existing patient safety classifications. The conceptual framework was iteratively improved through technical expert meetings and a two-stage web-based modified Delphi survey of over 250 international experts. This work culminated in a conceptual framework consisting of ten high level classes: incident type, patient outcomes, patient characteristics, incident characteristics, contributing factors/hazards, organizational outcomes, detection, mitigating factors, ameliorating actions and actions taken to reduce risk. While the framework for the ICPS is in place, several challenges remain. Concepts need to be defined, guidance for using the classification needs to be provided, and further real-world testing needs to occur to progressively refine the ICPS to ensure it is fit for purpos

Towards an International Classification for Patient Safety: the conceptual framework

Global advances in patient safety have been hampered by the lack of a uniform classification of patient safety concepts. This is a significant barrier to developing strategies to reduce risk, performing evidence-based research and evaluating existing healthcare policies relevant to patient safety. Since 2005, the World Health Organization's World Alliance for Patient Safety has undertaken the Project to Develop an International Classification for Patient Safety (ICPS) to devise a classification which transforms patient safety information collected from disparate systems into a common format to facilitate aggregation, analysis and learning across disciplines, borders and time. A drafting group, comprised of experts from the fields of patient safety, classification theory, health informatics, consumer/patient advocacy, law and medicine, identified and defined key patient safety concepts and developed an internationally agreed conceptual framework for the ICPS based upon existing patient safety classifications. The conceptual framework was iteratively improved through technical expert meetings and a two-stage web-based modified Delphi survey of over 250 international experts. This work culminated in a conceptual framework consisting of ten high level classes: incident type, patient outcomes, patient characteristics, incident characteristics, contributing factors/hazards, organizational outcomes, detection, mitigating factors, ameliorating actions and actions taken to reduce risk. While the framework for the ICPS is in place, several challenges remain. Concepts need to be defined, guidance for using the classification needs to be provided, and further real-world testing needs to occur to progressively refine the ICPS to ensure it is fit for purpose

Neighbourhood social and physical environment and general practitioner assessed morbidity.

The aim of our study was to investigate the association between health enhancing and threatening, and social and physical aspects of the neighbourhood environment and general practitioner (GP) assessed morbidity of the people living there, in order to find out whether the effects of environmental characteristics add up or modify each other. We combined GP electronic health records with environmental data on neighbourhoods in the Netherlands. Cross-classified logistic multilevel models show the importance of taking into account several environmental characteristics and confounders, as social capital effects on the prevalence of morbidity disappear when other area characteristics are taken into account. Stratification by area socio-economic status, shows that the association between environmental characteristics and the prevalence of morbidity is stronger for people living in low SES areas. In low SES areas, green space seems to alleviate effects of air pollution on the prevalence of high blood pressure and diabetes, while the effects of green space and social capital reinforce each other

Extracorporeal Photopheresis versus Anticytokine Therapy as a Second-Line Treatment for Steroid-Refractory Acute GVHD: A Multicenter Comparative Analysis

AbstractThe optimal therapy for steroid-refractory (SR) acute graft-versus-host disease (aGVHD) is undefined. We studied patients with SR aGVHD, comparing extracorporeal photopheresis (ECP; n = 57) and anticytokine therapy (n = 41). In multivariate analyses, ECP, adjusted for steroid dose (odds ratio, 3.42; P = .007), and grade >II aGVHD (odds ratio, 68; P < .001) were independent predictors of response. ECP therapy, adjusted for conditioning regimen intensity and steroid dose, was associated with superior survival (hazard ratio [HR], 4.6; P = .016) in patients with SR grade II aGVHD. Grade >II aGVHD at onset of salvage therapy (HR, 9.4; P < .001) and lack of response to therapy (HR, 3.09; P = .011) were associated with inferior survival. These findings require validation in a prospective randomized study

Health equity in the New Zealand health care system: a national survey

<p>Abstract</p> <p>Introduction</p> <p>In all countries people experience different social circumstances that result in avoidable differences in health. In New Zealand, Māori, Pacific peoples, and those with lower socioeconomic status experience higher levels of chronic illness, which is the leading cause of mortality, morbidity and inequitable health outcomes. Whilst the health system can enable a fairer distribution of good health, limited national data is available to measure health equity. Therefore, we sought to find out whether health services in New Zealand were equitable by measuring the level of development of components of chronic care management systems across district health boards. Variation in provision by geography, condition or ethnicity can be interpreted as inequitable.</p> <p>Methods</p> <p>A national survey of district health boards (DHBs) was undertaken on macro approaches to chronic condition management with detail on cardiovascular disease, chronic obstructive pulmonary disease, congestive heart failure, stroke and diabetes. Additional data from expert informant interviews on program reach and the cultural needs of Māori and Pacific peoples was sought. Survey data were analyzed on dimensions of health equity relevant to strategic planning and program delivery. Results are presented as descriptive statistics and free text. Interviews were transcribed and NVivo 8 software supported a general inductive approach to identify common themes.</p> <p>Results</p> <p>Survey responses were received from the majority of DHBs (15/21), some PHOs (21/84) and 31 expert informants. Measuring, monitoring and targeting equity is not systematically undertaken. The Health Equity Assessment Tool is used in strategic planning but not in decisions about implementing or monitoring disease programs. Variable implementation of evidence-based practices in disease management and multiple funding streams made program implementation difficult. Equity for Māori is embedded in policy, this is not so for other ethnic groups or by geography. Populations that conventional practitioners find hard to reach, despite recognized needs, are often underserved. Nurses and community health workers carried a disproportionate burden of care. Cultural and diversity training is not a condition of employment.</p> <p>Conclusions</p> <p>There is a struggle to put equity principles into practice, indicating will without enactment. Equity is not addressed systematically below strategic levels and equity does not shape funding decisions, program development, implementation and monitoring. Equity is not incentivized although examples of exceptional practice, driven by individuals, are evident across New Zealand.</p

Ten-year mortality after treating obstructive coronary atherosclerosis with contemporary stents in patients with or without concomitant peripheral arterial disease

Background and aims: Previous studies in percutaneous coronary intervention (PCI) patients showed a higher 3-year adverse event risk, including all-cause mortality, in those with concomitant peripheral arterial disease (PADs). Ten-year data of mortality and causes of death are scarce. This analysis assessed PCI patients, treated with contemporary drug-eluting stents, the impact of concomitant PADs on very long-term mortality, and causes of death. Methods: We assessed PCI all-comers from our center who participated in the TWENTE and DUTCH PEERS trials (clinicaltrials.gov:NCT01066650, NCT01331707), comparing patients with versus without PADs. Life status was checked in the Dutch Personal Records Database; causes of death were obtained from medical records. Results: Of 2705 study patients, 668 (24.7%) died during follow-up: 88/212 (41.5%) patients with PADs and 580/2493 (23.1%) without PADs. In PADs patients, the 10-year rate of all-cause mortality was about twice as high as in patients without PADs (41.5% vs.23.1%, HR: 2.05, 95%-CI: 1.64–2.57, p&lt;0.001). For both groups, the rates of patients dying from various causes of death were: cardiac (14.1% vs .6.8%), vascular (2.8% vs. 1.1%), non-cardiovascular (17.4% vs. 9.8%), and unclear causes (7.1% vs. 5.3%), without a statistically significant between-group difference. When multivariate analysis was adjusted for between-group differences in cardiovascular risk profile, PADs remained predictor of all-cause mortality (adjusted HR: 1.38, 95%-CI: 1.08–1.75, p=0.01). Conclusions: The 10-year all-cause mortality rate in PCI patients with concomitant PADs was almost twice as high as in those without PADs. Age and other traditional cardiovascular risk factors were higher in patients with PADs, but after correction for these confounders PADs still accounted for almost 40% increase in mortality.</p

Feasibility of a Monitoring Mechanism Supporting a Watch List under the Water Framework Directive

This report describes work conducted by the European Commission’s Joint Research Centre in the context of its support to the implementation of the Water Framework Directive 2000/60/EC. The work aimed at the feasibility assessment of an experimental monitoring exercise in support to a so-called Watch List Mechanism in a collaborative design involving EU Member States laboratories and some 200 official monitoring station operated by the Member States. The report includes all details on sampling stations, performance of analytical methods as well as the results of the analyses of all samples with regard to the occurrence and levels of 20 compounds of concern. In total, 219 whole water samples originating from 25 EU Member States and 2 other European countries, were assessed for contents of acesulfame, glyphosate and its metabolite AMPA, 1H-Benzotriazole and tolyltriazoles, bisphenol A, triclosan and triclocarban, carbamazepine and its metabolite 10,11-dihydro-10,11-dihydroxycarbamazepine, sulfamethoxazole, perfluoropropionic acid, tris-2-chloropropyl phosphate, methyl tert-butyl ether, silver, boron and chloride (Cl-) in water. Furthermore, 23 sediment samples were analysed for decabromodiphenylethane and decabromodiphenyl ether. The underlying analytical methods are carefully documented with regards to their performance characteristics. Obtained results are assessed statistically and where possible compared to other findings. Although the analysed single samples are insufficient to make any statement on the performance of the treatment processes leading to the compost, the collective of data allows having a glance at the pan-European situation as regards the studies compounds. Background information from literature describing the situation before the survey is included, too. The report is divided into a core part and two annexes. For practical reasons, the report is split into two volumes: Volume 1 contains the report and the single analytical results; volume 2 contains the documentation of the sampling stations.JRC.H.1-Water Resource