A randomized phase III study comparing dacarbazine, BCNU, cisplatin and tamoxifen with dacarbazine and interferon in advanced melanoma

The purpose of this study was to compare the response rate, overall and 1-year survival in patients with advanced melanoma treated with a standard therapy, dacarbazine and interferon-alpha (DTIC/IFN), or combination chemotherapy, consisting of dacarbazine, BCNU, cisplatin and tamoxifen (DBCT). Treatment toxicity and time spent in hospital were secondary end points. One hundred and five patients (of whom 100 were eligible) were randomized to receive either DTIC/IFN or DBCT. The trial was designed to detect a 25% absolute difference in response rate or in 1-year survival with 80% power. There was no significant difference in response rate: this was 17.3% with DTIC/IFN and 26.4% with DBCT. Median overall survival was similar at 199 and 202 days respectively. One-year survival rate favoured standard treatment (30.6 vs 22.6%), but did not differ significantly between arms. DBCT was associated with significantly greater haematological toxicity, and a greater need for time spent in hospital (5.75 days/treatment cycle vs 2.29 with dacarbazine and interferon). DBCT combination therapy cannot be recommended as standard treatment for advanced melanoma. Dacarbazine remains the standard chemotherapy for this condition. © 2000 Cancer Research Campaig

Respiratory viruses, symptoms, and inflammatory markers in acute exacerbations and stable chronic obstructive pulmonary disease

The effects of respiratory viral infection on the time course of chronic obstructive pulmonary disease (COPD) exacerbation were examined by monitoring changes in systemic inflammatory markers in stable COPD and at exacerbation. Eighty-three patients with COPD (mean [SD] age, 66.6 [7.1] yr, FEV1, 1.06 [0.61] L) recorded daily peak expiratory flow rate and any increases in respiratory symptoms. Nasal samples and blood were taken for respiratory virus detection by culture, polymerase chain reaction, and serology, and plasma fibrinogen and serum interleukin-6 (IL-6) were determined at stable baseline and exacerbation. Sixty-four percent of exacerbations were associated with a cold occurring up to 18 d before exacerbation. Seventy-seven viruses (39 [58.2%] rhinoviruses) were detected in 66 (39.2%) of 168 COPD exacerbations in 53 (64%) patients. Viral exacerbations were associated with frequent exacerbators, colds with increased dyspnea, a higher total symptom count at presentation, a longer median symptom recovery period of 13 d, and a tendency toward higher plasma fibrinogen and serum IL-6 levels. Non-respiratory syncytial virus (RSV) respiratory viruses were detected in 11 (16%), and RSV in 16 (23.5%), of 68 stable COPD patients, with RSV detection associated with higher inflammatory marker levels. Respiratory virus infections are associated with more severe and frequent exacerbations, and may cause chronic infection in COPD. Prevention and early treatment of viral infections may lead to a decreased exacerbation frequency and morbidity associated with COPD

Natural Genetic Variation in Selected Populations of Arabidopsis thaliana Is Associated with Ionomic Differences

Controlling elemental composition is critical for plant growth and development as well as the nutrition of humans who utilize plants for food. Uncovering the genetic architecture underlying mineral ion homeostasis in plants is a critical first step towards understanding the biochemical networks that regulate a plant's elemental composition (ionome). Natural accessions of Arabidopsis thaliana provide a rich source of genetic diversity that leads to phenotypic differences. We analyzed the concentrations of 17 different elements in 12 A. thaliana accessions and three recombinant inbred line (RIL) populations grown in several different environments using high-throughput inductively coupled plasma- mass spectroscopy (ICP-MS). Significant differences were detected between the accessions for most elements and we identified over a hundred QTLs for elemental accumulation in the RIL populations. Altering the environment the plants were grown in had a strong effect on the correlations between different elements and the QTLs controlling elemental accumulation. All ionomic data presented is publicly available at www.ionomicshub.org

Effect on life expectancy of temporal sequence in a multimorbidity cluster of psychosis, diabetes, and congestive heart failure among 1·7 million individuals in Wales with 20-year follow-up: a retrospective cohort study using linked data

BACKGROUND: To inform targeted public health strategies, it is crucial to understand how coexisting diseases develop over time and their associated impacts on patient outcomes and health-care resources. This study aimed to examine how psychosis, diabetes, and congestive heart failure, in a cluster of physical-mental health multimorbidity, develop and coexist over time, and to assess the associated effects of different temporal sequences of these diseases on life expectancy in Wales. METHODS: In this retrospective cohort study, we used population-scale, individual-level, anonymised, linked, demographic, administrative, and electronic health record data from the Wales Multimorbidity e-Cohort. We included data on all individuals aged 25 years and older who were living in Wales on Jan 1, 2000 (the start of follow-up), with follow-up continuing until Dec 31, 2019, first break in Welsh residency, or death. Multistate models were applied to these data to model trajectories of disease in multimorbidity and their associated effect on all-cause mortality, accounting for competing risks. Life expectancy was calculated as the restricted mean survival time (bound by the maximum follow-up of 20 years) for each of the transitions from the health states to death. Cox regression models were used to estimate baseline hazards for transitions between health states, adjusted for sex, age, and area-level deprivation (Welsh Index of Multiple Deprivation [WIMD] quintile). FINDINGS: Our analyses included data for 1 675 585 individuals (811 393 [48·4%] men and 864 192 [51·6%] women) with a median age of 51·0 years (IQR 37·0-65·0) at cohort entry. The order of disease acquisition in cases of multimorbidity had an important and complex association with patient life expectancy. Individuals who developed diabetes, psychosis, and congestive heart failure, in that order (DPC), had reduced life expectancy compared with people who developed the same three conditions in a different order: for a 50-year-old man in the third quintile of the WIMD (on which we based our main analyses to allow comparability), DPC was associated with a loss in life expectancy of 13·23 years (SD 0·80) compared with the general otherwise healthy or otherwise diseased population. Congestive heart failure as a single condition was associated with mean a loss in life expectancy of 12·38 years (0·00), and with a loss of 12·95 years (0·06) when preceded by psychosis and 13·45 years (0·13) when followed by psychosis. Findings were robust in people of older ages, more deprived populations, and women, except that the trajectory of psychosis, congestive heart failure, and diabetes was associated with higher mortality in women than men. Within 5 years of an initial diagnosis of diabetes, the risk of developing psychosis or congestive heart failure, or both, was increased. INTERPRETATION: The order in which individuals develop psychosis, diabetes, and congestive heart failure as combinations of conditions can substantially affect life expectancy. Multistate models offer a flexible framework to assess temporal sequences of diseases and allow identification of periods of increased risk of developing subsequent conditions and death. FUNDING: Health Data Research UK

Effect on life expectancy of temporal sequence in a multimorbidity cluster of psychosis, diabetes, and congestive heart failure among 1·7 million individuals in Wales with 20-year follow-up : a retrospective cohort study using linked data

Funding: This work was supported by Health Data Research UK (HDRUK) Measuring and Understanding Multimorbidity using Routine Data in the UK (MUrMuRUK; award numbers HDR-9006 and CFC0110). HDRUK is funded by the UK Medical Research Council (MRC), Engineering and Physical Sciences Research Council, Economic and Social Research Council, NIHR (England), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), British Heart Foundation, and Wellcome Trust. This work also was co-funded by the MRC and NIHR (grant number MR/S027750/1). The work was supported by the Administrative Data Research (ADR) Wales programme of work, part of the Economic and Social Research Council (part of UK Research and Innovation) funded ADR UK (grant ES/S007393/1). RKO is supported by a Springboard award (SBF006\1122) funded by the Academy of Medical Sciences, Wellcome Trust, Government Department of Business, Energy and Industrial Strategy, British Heart Foundation, and Diabetes UK. SS is part funded by the NIHR Applied Research Collaboration West Midlands, the NIHR Health Protection Research Unit (HPRU) in Gastrointestinal Infections, and the NIHR HPRU in Genomics and Enabling Data.Background To inform targeted public health strategies, it is crucial to understand how coexisting diseases develop over time and their associated impacts on patient outcomes and health-care resources. This study aimed to examine how psychosis, diabetes, and congestive heart failure, in a cluster of physical–mental health multimorbidity, develop and coexist over time, and to assess the associated effects of different temporal sequences of these diseases on life expectancy in Wales. Methods In this retrospective cohort study, we used population-scale, individual-level, anonymised, linked, demographic, administrative, and electronic health record data from the Wales Multimorbidity e-Cohort. We included data on all individuals aged 25 years and older who were living in Wales on Jan 1, 2000 (the start of follow-up), with follow-up continuing until Dec 31, 2019, first break in Welsh residency, or death. Multistate models were applied to these data to model trajectories of disease in multimorbidity and their associated effect on all-cause mortality, accounting for competing risks. Life expectancy was calculated as the restricted mean survival time (bound by the maximum follow-up of 20 years) for each of the transitions from the health states to death. Cox regression models were used to estimate baseline hazards for transitions between health states, adjusted for sex, age, and area-level deprivation (Welsh Index of Multiple Deprivation [WIMD] quintile). Findings Our analyses included data for 1 675 585 individuals (811 393 [48·4%] men and 864 192 [51·6%] women) with a median age of 51·0 years (IQR 37·0–65·0) at cohort entry. The order of disease acquisition in cases of multimorbidity had an important and complex association with patient life expectancy. Individuals who developed diabetes, psychosis, and congestive heart failure, in that order (DPC), had reduced life expectancy compared with people who developed the same three conditions in a different order: for a 50-year-old man in the third quintile of the WIMD (on which we based our main analyses to allow comparability), DPC was associated with a loss in life expectancy of 13·23 years (SD 0·80) compared with the general otherwise healthy or otherwise diseased population. Congestive heart failure as a single condition was associated with mean a loss in life expectancy of 12·38 years (0·00), and with a loss of 12·95 years (0·06) when preceded by psychosis and 13·45 years (0·13) when followed by psychosis. Findings were robust in people of older ages, more deprived populations, and women, except that the trajectory of psychosis, congestive heart failure, and diabetes was associated with higher mortality in women than men. Within 5 years of an initial diagnosis of diabetes, the risk of developing psychosis or congestive heart failure, or both, was increased. Interpretation The order in which individuals develop psychosis, diabetes, and congestive heart failure as combinations of conditions can substantially affect life expectancy. Multistate models offer a flexible framework to assess temporal sequences of diseases and allow identification of periods of increased risk of developing subsequent conditions and death.Publisher PDFPeer reviewe

An approach to numerical simulation of the gas distribution in the atmosphere of Enceladus

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94942/1/jgra20509.pd

Clustering long-term health conditions among 67728 people with multimorbidity using electronic health records in Scotland

Funding: CMC: This work was supported by Health Data Research UK (HDR UK) Measuring and Understanding Multimorbidity using Routine Data in the UK (HDR-9006; CFC0110). Health Data Research UK (HDR-9006) is funded by: UK Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, the National Institute for Health Research (England), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), British Heart Foundation, and Wellcome Trust.There is still limited understanding of how chronic conditions co-occur in patients with multimorbidity and what are the consequences for patients and the health care system. Most reported clusters of conditions have not considered the demographic characteristics of these patients during the clustering process. The study used data for all registered patients that were resident in Fife or Tayside, Scotland and aged 25 years or more on 1st January 2000 and who were followed up until 31st December 2018. We used linked demographic information, and secondary care electronic health records from 1st January 2000. Individuals with at least two of the 31 Elixhauser Comorbidity Index conditions were identified as having multimorbidity. Market basket analysis was used to cluster the conditions for the whole population and then repeatedly stratified by age, sex and deprivation. 318,235 individuals were included in the analysis, with 67,728 (21·3%) having multimorbidity. We identified five distinct clusters of conditions in the population with multimorbidity: alcohol misuse, cancer, obesity, renal failure, and heart failure. Clusters of long-term conditions differed by age, sex and socioeconomic deprivation, with some clusters not present for specific strata and others including additional conditions. These findings highlight the importance of considering demographic factors during both clustering analysis and intervention planning for individuals with multiple long-term conditions. By taking these factors into account, the healthcare system may be better equipped to develop tailored interventions that address the needs of complex patients.Publisher PDFPeer reviewe

Clustering long-Term health conditions among 67728 people with multimorbidity using electronic health records in Scotland

There is still limited understanding of how chronic conditions co-occur in patients with multimorbidity and what are the consequences for patients and the health care system. Most reported clusters of conditions have not considered the demographic characteristics of these patients during the clustering process. The study used data for all registered patients that were resident in Fife or Tayside, Scotland and aged 25 years or more on 1st January 2000 and who were followed up until 31st December 2018. We used linked demographic information, and secondary care electronic health records from 1st January 2000. Individuals with at least two of the 31 Elixhauser Comorbidity Index conditions were identified as having multimorbidity. Market basket analysis was used to cluster the conditions for the whole population and then repeatedly stratified by age, sex and deprivation. 318,235 individuals were included in the analysis, with 67,728 (21-3%) having multimorbidity. We identified five distinct clusters of conditions in the population with multimorbidity: Alcohol misuse, cancer, obesity, renal failure, and heart failure. Clusters of long-Term conditions differed by age, sex and socioeconomic deprivation, with some clusters not present for specific strata and others including additional conditions. These findings highlight the importance of considering demographic factors during both clustering analysis and intervention planning for individuals with multiple long-Term conditions. By taking these factors into account, the healthcare system may be better equipped to develop tailored interventions that address the needs of complex patients.</p

Measurement of χ c1 and χ c2 production with s√ = 7 TeV pp collisions at ATLAS

The prompt and non-prompt production cross-sections for the χ c1 and χ c2 charmonium states are measured in pp collisions at s√ = 7 TeV with the ATLAS detector at the LHC using 4.5 fb−1 of integrated luminosity. The χ c states are reconstructed through the radiative decay χ c → J/ψγ (with J/ψ → μ + μ −) where photons are reconstructed from γ → e + e − conversions. The production rate of the χ c2 state relative to the χ c1 state is measured for prompt and non-prompt χ c as a function of J/ψ transverse momentum. The prompt χ c cross-sections are combined with existing measurements of prompt J/ψ production to derive the fraction of prompt J/ψ produced in feed-down from χ c decays. The fractions of χ c1 and χ c2 produced in b-hadron decays are also measured