Quality of care assessment for people with multimorbidity.

Multimorbidity, the simultaneous presence of multiple health conditions in an individual, is an increasingly common phenomenon globally. The systematic assessment of the quality of care delivered to people with multimorbidity will be key to informing the organization of services for meeting their complex needs. Yet, current assessments tend to focus on single conditions and do not capture the complex processes that are required for providing care for people with multimorbidity. We conducted a scoping review on quality of care and multimorbidity in selected databases in June 2018 and identified 87 documents as eligible for review, predominantly original research and reviews from North America, Europe and Australasia and mostly frequently related to primary care settings. We synthesized data qualitatively in terms of perceived challenges, evidence and proposed metrics. Findings reveal that the association between quality of care and multimorbidity is complex and depends on the conditions involved (quality appears to be higher for those with concordant conditions, and lower in the presence of discordant conditions) and the approach used for measuring quality (quality appears to be higher in people with multimorbidity when measured using condition/drug-specific process or intermediate outcome indicators, and worse when using patient-centred reports of experiences of care). People with discordant multimorbidity may be disadvantaged by current approaches to quality assessment, particularly when they are linked to financial incentives. A better understanding of models of care that best meet the needs of this group is needed for developing appropriate quality assessment frameworks. Capturing patient preferences and values and incorporate patients' voices in the form of patient-reported experiences and outcomes of care will be critical towards the achievement of high-performing health systems that are responsive to the needs of people with multimorbidity.

Amenable mortality in the EU-has the crisis changed its course?

Background: Did the global financial crisis and its aftermath impact upon the performance of health systems in Europe? We investigated trends in amenable and other mortality in the EU since 2000 across 28 EU countries. Methods: We use WHO detailed mortality files from 28 EU countries to calculate age-standardized deaths rates from amenable and other causes. We then use joinpoint regression to analyse trends in mortality before and after the onset of the economic crisis in Europe in 2008. Results: Amenable and other mortality have declined in the EU since 2000, albeit faster for amenable mortality. We observed increases in amenable mortality following the global financial crisis for females in Estonia [from -4.53 annual percentage change (APC) in 2005-12 to 0.03 APC in 2012-14] and Slovenia (from -4.22 APC in 2000-13 to 0.73 in 2013-15) as well as males and females in Greece(males: from -2.93 APC in 2000-10 to 0.01 APC in 2010-13; females: from -3.48 APC in 2000-10 to 0.06 APC in 2010-13). Other mortality continued to decline for these populations. Increases in deaths from infectious diseases before and after the crisis played a substantial part in reversals in Estonia, Slovenia and Greece. Conclusion: There is evidence that amenable mortality rose in Greece and, among females in Estonia and Slovenia. However, in most countries, trends in amenable mortality rates appeared to be unaffected by the crisis.

Homozygous G/G variant of SNP309 in the human MDM2 gene is associated with earlier tumor onset in Caucasian female renal cell carcinoma patients.

Human mouse double minute 2 (Mdm2) plays an essential role in the regulation of the tumor suppressor p53. The G/G variant of SNP309 was shown to increase Mdm2 mRNA/protein expression and to be associated with an increased risk and earlier onset of different cancers in Asian populations. However, the frequency and impact of these G/G variants have not been studied in Caucasian renal cell carcinoma (RCC) patients. Therefore, we analyzed an unselected German cohort of 197 consecutive RCC patients and detected the G/G variant in 18 (9.1%) patients, the G/T variant in 116 (58.9%) patients and the T/T variant in 63 (32.0%) patients. Studying the association between age at tumor onset and SNP309 genotypes, no correlation was detected in the entire RCC cohort or among the male RCC patients. However, the female G/G patients (median age 59.5 years) were diagnosed 13.5 years earlier than the T/T females (median age 73 years). When separating all females into two groups at their median age (68 years), 7 and 1 patients with the G/G variant and 9 and 13 patients with the T/T variant were noted in these age groups (P=0.024). To study the age dependency of tumor onset further, a second, age-selected cohort of 205 RCC patients was investigated, which comprised especially young and old patients. Interestingly, the G/G type occurred more often at lower tumor stages and tumor grades compared with higher stages (P=0.039 and 0.004, respectively). In females, the percentage of the G/G variant was only slightly higher in the younger age group, whereas in males, the percentage of the G/G variant was remarkably higher in the younger age group (19.4% vs 8.0%). In summary, female Caucasian RCC patients with the MDM2 SNP309 G/G genotype showed significantly earlier tumor onset than patients with the wild-type T/T genotype.

A diamond-based scanning probe spin sensor operating at low temperature in ultra-high vacuum.

We present the design and performance of an ultra-high vacuum (UHV) low temperature scanning probe microscope employing the nitrogen-vacancy color center in diamond as an ultrasensitive magnetic field sensor. Using this center as an atomic-size scanning probe has enabled imaging of nanoscale magnetic fields and single spins under ambient conditions. In this article we describe an experimental setup to operate this sensor in a cryogenic UHV environment. This will extend the applicability to a variety of molecular systems due to the enhanced target spin lifetimes at low temperature and the controlled sample preparation under UHV conditions. The instrument combines a tuning-fork based atomic force microscope (AFM) with a high numeric aperture confocal microscope and the facilities for application of radio-frequency (RF) fields for spin manipulation. We verify a sample temperature of <50 K even for strong laser and RF excitation and demonstrate magnetic resonance imaging with a magnetic AFM tip.

SCOPE: a scorecard for osteoporosis in Europe.

SUMMARY: The scorecard summarises key indicators of the burden of osteoporosis and its management in each of the member states of the European Union. The resulting scorecard elements were then assembled on a single sheet to provide a unique overview of osteoporosis in Europe. INTRODUCTION: The scorecard for osteoporosis in Europe (SCOPE) is an independent project that seeks to raise awareness of osteoporosis care in Europe. The aim of this project was to develop a scorecard and background documents to draw attention to gaps and inequalities in the provision of primary and secondary prevention of fractures due to osteoporosis. METHODS: The SCOPE panel reviewed the information available on osteoporosis and the resulting fractures for each of the 27 countries of the European Union (EU27). The information researched covered four domains: background information (e.g. the burden of osteoporosis and fractures), policy framework, service provision and service uptake e.g. the proportion of men and women at high risk that do not receive treatment (the treatment gap). RESULTS: There was a marked difference in fracture risk among the EU27. Of concern was the marked heterogeneity in the policy framework, service provision and service uptake for osteoporotic fracture that bore little relation to the fracture burden. For example, despite the wide availability of treatments to prevent fractures, in the majority of the EU27, only a minority of patients at high risk receive treatment for osteoporosis even after their first fracture. The elements of each domain in each country were scored and coded using a traffic light system (red, orange, green) and used to synthesise a scorecard. The resulting scorecard elements were then assembled on a single sheet to provide a unique overview of osteoporosis in Europe. CONCLUSIONS: The scorecard will enable healthcare professionals and policy makers to assess their country's general approach to the disease and provide indicators to inform future provision of healthcare.

MicroRNA profiles classify papillary renal cell carcinoma subtypes.

BACKGROUND: Besides the conventional clear-cell renal cell carcinoma (ccRCC), papillary RCC (pRCC) is the second most common renal malignancy. Papillary RCCs can further be subdivided into two distinct subtypes. Although a clinical relevance of pRCC subtyping has been shown, little is known about the molecular characteristics of both pRCC subtypes. METHODS: We performed microarray-based microRNA (miRNA) expression profiling of primary ccRCC and pRCC cases. A subset of miRNAs was identified and used to establish a classification model for ccRCC, pRCC types 1 and 2 and normal tissue. Furthermore, we performed gene set enrichment analysis with the predicted miRNA target genes. RESULTS: Only five miRNAs (miR-145, -200c, -210, -502-3p and let-7c) were sufficient to identify the samples with high accuracy. In a collection of 111 tissue samples, 73.9% were classified correctly. An enrichment of miRNA target genes in the family of multidrug-resistance proteins was noted in all tumours. Several components of the Jak-STAT signalling pathway might be targets for miRNAs that define pRCC tumour subtypes. CONCLUSION: MicroRNAs are able to accurately classify RCC samples. Deregulated miRNAs might contribute to the high chemotherapy resistance of RCC. Furthermore, our results indicate that pRCC type 2 tumours could be dependent on oncogenic MYC signalling.

Properties of uniform diameter InN nanowires obtained under Si doping.

High quality, well-separated, homogeneous sizes and high aspect ratio Si-doped InN nanowires (NWs) were grown by catalyst-free molecular beam epitaxy (MBE) after optimization of the growth conditions. To this end, statistical analysis of NW density and size distribution was performed. The high crystal quality and smooth NW surfaces were observed by high resolution transmission electron microscopy. Spectral photoluminescence has shown the increase of the band filling effect with Si flux, indicating successful n-type doping. A Raman LO scattering mode appears with a pronounced low energy tail, also reported for highly doped InN films.

[Plasmacytoid and micropapillary urothelial carcinoma: rare forms of urothelial carcinoma]. / Das plasmazytoide und mikropapilläre Urothelkarzinom : Seltene Varianten eines Urothelkarzinoms.

Plasmacytoid urothelial carcinomas (PUC) along with micropapillary urothelial carcinoma (MPC), small cell cancer, and nested-typed tumors are among the rare variations of urothelial carcinomas. The molecular characterization of PUC and MPC is currently the focus of our research on bladder cancer which we are conducting in cooperation with the Institute of Pathology in Erlangen. PUCs account for approximately 0.9% of all urothelial carcinomas. The diagnosis of these rare variants has acquired increasing importance since this may have prognostic and possibly therapeutic consequences for the patients. By analysis of 32 PUCs we were able to demonstrate the most comprehensive results available to date on the underlying molecular and clinical characteristics of these variants. Micropapillary cancers have already been described in multiple organs. Micropapillary breast cancer represent an individual entity with characteristic genomic aberrations and corresponding clinical and pathological features.

Anthropogenic 129I in the atmosphere: overview over major sources, transport processes and deposition pattern.

Wet and, to a lesser extent, dry deposition of atmospheric (129)I are known to represent the dominating processes responsible for (129)I in continental environmental samples that are remote from (129)I sources and not directly influenced by any liquid (129)I release of nuclear installations. Up to now, however, little is known about the major emitters and the related global deposition pattern of (129)I. In this work an overview over major sources of (129)I is given, and hitherto unknown time-dependent releases from these were estimated. Total gaseous (129)I releases from the US and former Soviet reprocessing facilities Hanford, Savannah River, Mayak, Seversk and Zheleznogorsk were found to have been 0.53, 0.27, 1.05, 0.23 and 0.14TBq, respectively. These facilities were thus identified as major airborne (129)I emitters. The global deposition pattern due to the (129)I released, depending on geographic latitude and longitude, and on time was studied using a box model describing the global atmospheric transport and deposition of (129)I. The model predictions are compared to (129)I concentrations measured by means of Accelerator Mass Spectrometry (AMS) in water samples that were collected from various lakes in Asia, Africa, America and New Zealand, and to published values. As a result, both pattern and temporal evolution of (129)I deposition values measured in and calculated for different types of environmental samples are, in general, in good agreement. This supports our estimate on atmospheric (129)I releases and the considered substantial transport and deposition mechanisms in our model calculations.

Enhanced light scattering of the forbidden longitudinal optical phonon mode studied by micro-Raman spectroscopy on single InN nanowires.

In the literature, there are controversies on the interpretation of the appearance in InN Raman spectra of a strong scattering peak in the energy region of the unscreened longitudinal optical (LO) phonons, although a shift caused by the phonon-plasmon interaction is expected for the high conductance observed in this material. Most measurements on light scattering are performed on ensembles of InN nanowires (NWs). However, it is important to investigate the behavior of individual nanowires and here we report on micro-Raman measurements on single nanowires. When changing the polarization direction of the incident light from parallel to perpendicular to the wire, the expected reduction of the Raman scattering was observed for transversal optical (TO) and E(2) phonon scattering modes, while a strong symmetry-forbidden LO mode was observed independently on the laser polarization direction. Single Mg- and Si-doped crystalline InN nanowires were also investigated. Magnesium doping results in a sharpening of the Raman peaks, while silicon doping leads to an asymmetric broadening of the LO peak. The results can be explained based on the influence of the high electron concentration with a strong contribution of the surface accumulation layer and the associated internal electric field.

Intercomparison study on (152)Eu gamma ray and (36)Cl AMS measurements for development of the new Hiroshima-Nagasaki Atomic Bomb Dosimetry System 2002 (DS02).

In the process of developing a new dosimetry system for atomic bomb survivors in Hiroshima and Nagasaki (DS02), an intercomparison study between (152)Eu and (36)Cl measurements was proposed, to reconcile the discrepancy previously observed in the Hiroshima data between measurements and calculations of thermal neutron activation products. Nine granite samples, exposed to the atomic-bomb radiation in Hiroshima within 1,200 m of the hypocenter, as well as mixed standard solutions containing known amounts of europium and chlorine that were neutron-activated by a (252)Cf source, were used for the intercomparison. Gamma-ray spectrometry for (152)Eu was carried out with ultra low-background Ge detectors at the Ogoya Underground Laboratory, Kanazawa University, while three laboratories participated in the (36)Cl measurement using accelerator mass spectrometry (AMS): The Technical University of Munich, Germany, the Lawrence Livermore National Laboratory, USA and the University of Tsukuba, Japan. Measured values for the mixed standard solutions showed good agreement among the participant laboratories. They also agreed well with activation calculations, using the neutron fluences monitored during the (252)Cf irradiation, and the corresponding activation cross-sections taken from the JENDL-3.3 library. The measured-to-calculated ratios obtained were 1.02 for (152)Eu and 0.91-1.02 for (36)Cl, respectively. Similarly, the results of the granite intercomparison indicated good agreement with the DS02 calculation for these samples. An average measured-to-calculated ratio of 0.98 was obtained for all granite intercomparison measurements. The so-called neutron discrepancy that was previously observed and that which included increasing measured-to-calculated ratios for thermal neutron activation products for increasing distances beyond 1,000 m from the hypocenter was not seen in the results of the intercomparison study. The previously claimed discrepancy could be explained by insufficient understanding of the measured data.

The changing regional pattern of ischaemic heart disease mortality in southern Europe: still healthy but uneven progress.

AIMS: To describe the evolving regional pattern of mortality from ischaemic heart disease (IHD) in five countries in southern Europe. METHODS: We analyse the changing pattern of IHD mortality among men and women aged 30-74 years in the standard regions of France, Greece, Italy, Portugal and Spain between 1994 and 2001 using routine data. RESULTS: Greece and, to some degree, Spain saw little improvement in IHD mortality in the second half of the 1990s. By contrast, IHD mortality among Portuguese women more than halved during this period. However, in some countries national declines in mortality masked increased regional variation in IHD mortality in some populations (Greece, women). Other countries such as Italy became increasingly homogeneous. CONCLUSION: Our analyses of the available mortality data show that not only are there differences in IHD mortality between and within the countries of this region, but that these are changing relatively rapidly. A combination of changes in lifestyle and in the delivery of health care could be responsible for this changing situation. Some countries have achieved less than might be expected based on common assumptions about healthy lifestyles and there is a danger of complacency. Other countries need to increase efforts to ensure that achievements in reducing IHD mortality are enjoyed by all.

129I measurements in lake water for an estimate of regional 129I depositions.

Estimates of (129)I depositions from (129)I releases of reprocessing plants are so far based on measurements of soil and rain water samples. Because (129)I concentrations in these samples show a highly temporal and spatial variability, the (129)I deposition values deduced from single measurements cannot be seen as representative for a larger area. Here it is proposed to use lake water as an archive for former (129)I depositions, to overcome these limitations. If the limnological parameters of any lake are known, the local (129)I deposition flux can be deduced which is temporally averaged over the flushing time, and spatially averaged over the catchment area of the lake. Samples were collected from various European lakes and from Lake Baikal (Russia). The (129)I concentration in these samples was measured by means of accelerator mass spectrometry, and values between 0.3 and 8.1x10(8) at/l were obtained. Deduced (129)I deposition fluxes averaged over the flushing times of the lakes range from 0.3 to 9.3x10(12) at/m(2) y. The (129)I deposition fluence measured for Lake Baikal is attributed predominantly to releases from the former Soviet reprocessing facilities Chelyabinsk, Tomsk and Krasnoyarsk, while the (129)I deposition fluxes deduced for all other lakes are attributed to releases from the European reprocessing activities at Sellafield, Marcoule and La Hague.

Investigation of the aluminium biokinetics in humans: a 26Al tracer study.

Despite the well-known toxicity of aluminium in chronic renal failure, a solid database on its biokinetics has been difficult to establish. A highly sensitive method using (26)Al as tracer and accelerator mass spectrometry (AMS) for detection was used. No perturbing background and saturation effects were taken into account using a delta function input of aluminium in time. Aluminium absorption, distribution, speciation and excretion in six healthy volunteers and in two patients with chronic renal failure were investigated following administration of a single oral or i.v. dose of (26)Al. Serial samples of blood and urine were taken. In a speciation study, the time dependence of the binding of (26)Al to low-molecular weight molecules in serum was investigated. The measured data were compared and interpreted with simulations in an open compartmental model. Fractional absorption, distribution, excretion and time constants for the aluminium transport were determined. Typical intestinal absorption rates for AlCl(3) were found to be in the range of 10(-3). The ultrafiltrable percentage of aluminium in serum of one volunteer was estimated to be 5.6+/-0.8%. Differences between healthy volunteers and patients with chronic renal failure were deduced. The employed method using (26)Al and ams has proven to be highly sensitive for investigations of aluminium biokinetics at the ultra-trace element level. With the model, the measured values of (26)Al in serum and urine were used to precisely determine absorption, speciation, distribution, retention and excretion of aluminium in humans.

A comparison of the alcohol-attributable mortality in four European countries.

BACKGROUND: Deaths due to alcohol consumption are an important component of all-cause mortality, particularly premature mortality. However, there are considerable regional variations, the reasons for which are unclear. METHODS: Estimates were made as reliably as possibly using vital statistics and best estimates of risk of the alcohol-attributable mortality, by age, sex and cause for four European countries (England and Wales, Germany, Denmark and Italy). Twenty-seven alcohol-related conditions were considered including the possible cardio-protective effects of alcohol. RESULTS: It was estimated that there are approximately 2% fewer deaths annually in England and Wales than would be expected in a non-drinking population and 0.3% fewer deaths among East German females. In West Germany, Denmark, Italy and among East German males there are more deaths caused by alcohol than are prevented (between 0.7 and 2.6% of all deaths). The highest age-specific proportion of alcohol-attributable deaths is found in East Germany where around 30% of deaths among males aged 25-44 years are due to drinking. Among young men in all four countries the largest contributor to alcohol-related deaths is road traffic accidents involving alcohol. CONCLUSIONS: Possible explanations for the variation in alcohol-attributable deaths between countries include different underlying heart disease rates, different patterns of alcohol consumption and beverage preferences, and different use of mortality classification. Differences in the reported alcohol consumption levels explain little of the variation in alcohol-attributable deaths. Estimating alcohol-attributable mortality by age and sex across countries may be a useful indicator for developing alcohol strategies and exploring ways of preventing premature mortality.

36Cl measurements in Hiroshima granite samples as part of an international intercomparison study. Results from the Munich group.

Within the effort to resolve the so-called Hiroshima neutron discrepancy, an international intercomparison study has been carried out on granite samples from Hiroshima, with participating institutions from Japan, the US, and Germany. (36)Cl and (152)Eu produced in these samples by thermal neutrons from the A-bomb explosion were assessed independently by means of different techniques. At the Maier-Leibnitz-Laboratory near Munich, Germany, (36)Cl concentrations were measured by accelerator mass spectrometry. Measured (36)Cl/Cl ratios ranged from 1,670 x 10(-13) (at a distance of 146 m from the hypocenter) to 2.2 x 10(-13) (at a distance of 1,163 m from the hypocenter). One granite sample not exposed to A-bomb neutrons was measured as a control, and a (36)Cl/Cl ratio of 2.6 x 10(-13) was obtained. On average, our experimental results are 20-30% lower than those provided by model calculations based on the dosimetry system DS86. The results presented here do not support previous assessments of (36)Cl, (60)Co, and (152)Eu which had suggested much larger thermal neutron fluences than those calculated on the basis of DS86 for distances from the hypocenter of more than 1,000 m.

Changing life expectancy in Romania after the transition.

BACKGROUND: While Poland, Hungary, and the Czech Republic have seen impressive gains in life expectancy in the 1990s, Romania has not. In contrast with the other countries, there has been very little research on the causes of the pattern of mortality seen in Romania. OBJECTIVES: To describe the trends in life expectancy at birth in Romania after the political transition in 1989 and to evaluate the contribution of deaths from different causes and different ages to these changes. METHODS: Decomposition of life expectancy by age and cause of death using routine data on mortality for the years 1990, 1996, and 1998; comparison of death rates by age, sex, and cause of death. RESULTS: Romania has experienced an overall decline of 1.71 years of life expectancy at birth from 1990 to 1996 in men and 0.54 years in women. The major contribution to this decline was an increase in mortality from cardiovascular diseases and diseases of the digestive system, in particular cirrhosis, among the middle aged and elderly. The recovery observed in 1998, of 1.12 years in men and 0.89 years in women, was mainly caused by a reduction in deaths from cardiovascular disease in the middle aged and elderly. Infant and early childhood mortality fell throughout the period but there was an increase of approximately 40% in mortality at age 5-9 that was almost entirely attributable to AIDS. CONCLUSION: This is the first Romanian study that describes the evolution of life expectancy after transition. Romania may at last be beginning to follow the path of improving adult mortality seen in the early 1990s in some of its neighbours. It has, however, been unique in eastern Europe in experiencing increasing childhood mortality. This is attributable to an epidemic of paediatric AIDS, consequent on the tragically inappropriate policies adopted in the 1980s.

What is happening to the health of the Croatian population?

AIM: To describe the problems in the interpretation of Croatian mortality data and explore possible reasons for the recorded increase in mortality in the 1990-1999 period, particularly related to different methods of collection and estimation of data on deaths and population. METHODS: Numbers of recorded deaths and population estimates were first obtained from the Croatian Institute for Public Health and examined in detail. The Institute used population estimates supplied by the Croatian Statistics Bureau, which included de jure population data (including all Croatian citizens wherever they live) until 1996 and de facto population data (including only population living in Croatia at least for a year, irrespective of citizenship) since 1996. A different set of population estimates based on de facto estimates since 1992 was obtained from the Croatian Bureau of Statistics. We examined trends in age- and sex-specific death rates from major causes in 1990-1999 period, using the mortality data from the Croatian Institute for Public Health and both sets of population estimates. Lung cancer as a cause of death was examined in more detail, since it is relatively stable over short periods of time. Interviews were undertaken with key informants to identify the reasons for any discrepancies. RESULTS: In Croatia, relatively stable death rates from lung cancer in men ranged from 84/100,000 in 1990 to 79/ 100,000 in 1995. In 1996, a marked discontinuity appeared in the Croatian data, with a 14% increase compared to 1995 (from 79/100,000 to 91/100,000) and a further increase in 1999 (94/100,000), which is not credible on the basis of the natural history of lung cancer. Analysis of mortality rates with de facto population estimates showed more gradual increase from 1992-1996. Methods used to estimate population and mortality during the 1990s were inconsistent and misleading. At present, it is impossible to be certain about the true level of mortality in Croatia during 1990s, as the numerator (deaths) and denominator (population) were incompatible until 1998. CONCLUSION: Major problems in data collection would have been identified if the investigation of unexpected mortality trends in Croatia in the 1990s had been done. Systematic analysis of health patterns should be done as soon as data from the 2001 census become available. Capacities in public health should be strengthened to make this possible. This issue has received little recognition from the international donor organizations, particularly those that use health data.