Economic evaluation of posaconazole versus fluconazole prophylaxis in patients with graft-versus-host disease (GVHD) in the Netherlands

The objective of this study was to evaluate the cost-effectiveness of posaconazole versus fluconazole for the prevention of invasive fungal infections (IFI) in graft-versus-host disease (GVHD) patients in the Netherlands. A decision analytic model was developed based on a double-blind randomized trial that compared posaconazole with fluconazole antifungal prophylaxis in recipients of allogeneic HSCT with GVHD who were receiving immunosuppressive therapy (Ullmann et al., N Engl J Med 356:335–347, 2007). Clinical events were modeled with chance nodes reflecting probabilities of IFIs, IFI-related death, and death from other causes. Data on life expectancy, quality-of-life, medical resource consumption, and costs were obtained from the literature. The total cost with posaconazole amounted to €9,428 (95% uncertainty interval €7,743–11,388), which is €4,566 (€2,460–6,854) more than those with fluconazole. Posaconazole prophylaxis resulted in 0.17 (0.02–0.36) quality adjusted life year (QALY) gained compared to fluconazole prophylaxis, corresponding to an incremental cost effectiveness ratio (ICER) of €26,225 per QALY gained. A scenario analysis demonstrated that at an increased background IFI risk (from 9% to 15%) the ICER was €13,462 per QALY. Given the underlying data and assumptions, posaconazole prophylaxis is expected to be cost-effective relative to fluconazole in recipients of allogeneic HSCT developing GVHD in the Netherlands. The cost-effectiveness of posaconazole depends on the IFI risk, which can vary by hospital

Comparative Proteomic Analysis of Serum from Patients with Systemic Sclerosis and Sclerodermatous GVHD. Evidence of Defective Function of Factor H

BACKGROUND: Systemic sclerosis (SSc) is an autoimmune disease characterized by immunological and vascular abnormalities. Until now, the cause of SSc remains unclear. Sclerodermatous graft-versus-host disease (ScGVHD) is one of the most severe complications following bone marrow transplantation (BMT) for haematological disorders. Since the first cases, the similarity of ScGVHD to SSc has been reported. However, both diseases could have different etiopathogeneses. The objective of this study was to identify new serum biomarkers involved in SSc and ScGVHD. METHODOLOGY: Serum was obtained from patients with SSc and ScGVHD, patients without ScGVHD who received BMT for haematological disorders and healthy controls. Bi-dimensional electrophoresis (2D) was carried out to generate maps of serum proteins from patients and controls. The 2D maps underwent image analysis and differently expressed proteins were identified. Immuno-blot analysis and ELISA assay were used to validate the proteomic data. Hemolytic assay with sheep erythrocytes was performed to evaluate the capacity of Factor H (FH) to control complement activation on the cellular surface. FH binding to endothelial cells (ECs) was also analysed in order to assess possible dysfunctions of this protein. PRINCIPAL FINDINGS: Fourteen differentially expressed proteins were identified. We detected pneumococcal antibody cross-reacting with double stranded DNA in serum of all bone marrow transplanted patients with ScGVHD. We documented higher levels of FH in serum of SSc and ScGVHD patients compared healthy controls and increased sheep erythrocytes lysis after incubation with serum of diffuse SSc patients. In addition, we observed that FH binding to ECs was reduced when we used serum from these patients. CONCLUSIONS: The comparative proteomic analysis of serum from SSc and ScGVHD patients highlighted proteins involved in either promoting or maintaining an inflammatory state. We also found a defective function of Factor H, possibly associated with ECs damage

Life expectancy associated with different ages at diagnosis of type 2 diabetes in high-income countries: 23 million person-years of observation

Background: The prevalence of type 2 diabetes is increasing rapidly, particularly among younger age groups. Estimates suggest that people with diabetes die, on average, 6 years earlier than people without diabetes. We aimed to provide reliable estimates of the associations between age at diagnosis of diabetes and all-cause mortality, cause-specific mortality, and reductions in life expectancy. Methods: For this observational study, we conducted a combined analysis of individual-participant data from 19 high-income countries using two large-scale data sources: the Emerging Risk Factors Collaboration (96 cohorts, median baseline years 1961–2007, median latest follow-up years 1980–2013) and the UK Biobank (median baseline year 2006, median latest follow-up year 2020). We calculated age-adjusted and sex-adjusted hazard ratios (HRs) for all-cause mortality according to age at diagnosis of diabetes using data from 1 515 718 participants, in whom deaths were recorded during 23·1 million person-years of follow-up. We estimated cumulative survival by applying age-specific HRs to age-specific death rates from 2015 for the USA and the EU. Findings: For participants with diabetes, we observed a linear dose–response association between earlier age at diagnosis and higher risk of all-cause mortality compared with participants without diabetes. HRs were 2·69 (95% CI 2·43–2·97) when diagnosed at 30–39 years, 2·26 (2·08–2·45) at 40–49 years, 1·84 (1·72–1·97) at 50–59 years, 1·57 (1·47–1·67) at 60–69 years, and 1·39 (1·29–1·51) at 70 years and older. HRs per decade of earlier diagnosis were similar for men and women. Using death rates from the USA, a 50-year-old individual with diabetes died on average 14 years earlier when diagnosed aged 30 years, 10 years earlier when diagnosed aged 40 years, or 6 years earlier when diagnosed aged 50 years than an individual without diabetes. Using EU death rates, the corresponding estimates were 13, 9, or 5 years earlier. Interpretation: Every decade of earlier diagnosis of diabetes was associated with about 3–4 years of lower life expectancy, highlighting the need to develop and implement interventions that prevent or delay the onset of diabetes and to intensify the treatment of risk factors among young adults diagnosed with diabetes. Funding: British Heart Foundation, Medical Research Council, National Institute for Health and Care Research, and Health Data Research UK

Use of Repeated Blood Pressure and Cholesterol Measurements to Improve Cardiovascular Disease Risk Prediction: An Individual-Participant-Data Meta-Analysis

The added value of incorporating information from repeated measurements of blood pressure and cholesterol for cardiovascular disease (CVD) risk prediction has not been rigorously assessed. We used data from the Emerging Risk Factors Collaboration on 191,445 adults (38 cohorts from across 17 countries with data from 1962-2014) with > 1 million measurements of systolic blood pressure, total cholesterol and high-density lipoprotein cholesterol; over a median 12 years of follow-up, 21,170 CVD events occurred. Risk prediction models using cumulative means of repeated measurements and summary measures from longitudinal modelling of the repeated measurements were compared to models using measurements from a single time point. Risk discrimination (C-index) and net reclassification were calculated, and changes in C-indices were meta-analysed across studies. Compared to the single time point model, the cumulative means and the longitudinal models increased the C-index by 0.0040 (95% CI: 0.0023, 0.0057) and 0.0023 (0.0005, 0.0042), respectively. Reclassification was also improved in both models; compared to the single time point model, overall net reclassification improvements were 0.0369 (0.0303, 0.0436) for the cumulative means model and 0.0177 (0.0110, 0.0243) for the longitudinal model. In conclusion, incorporating repeated measurements of blood pressure and cholesterol into CVD risk prediction models slightly improves risk prediction

Identification of Novel Genetic Markers Associated with Clinical Phenotypes of Systemic Sclerosis through a Genome-Wide Association Strategy

Contains fulltext : 97006.pdf (publisher's version ) (Open Access)The aim of this study was to determine, through a genome-wide association study (GWAS), the genetic components contributing to different clinical sub-phenotypes of systemic sclerosis (SSc). We considered limited (lcSSc) and diffuse (dcSSc) cutaneous involvement, and the relationships with presence of the SSc-specific auto-antibodies, anti-centromere (ACA), and anti-topoisomerase I (ATA). Four GWAS cohorts, comprising 2,296 SSc patients and 5,171 healthy controls, were meta-analyzed looking for associations in the selected subgroups. Eighteen polymorphisms were further tested in nine independent cohorts comprising an additional 3,175 SSc patients and 4,971 controls. Conditional analysis for associated SNPs in the HLA region was performed to explore their independent association in antibody subgroups. Overall analysis showed that non-HLA polymorphism rs11642873 in IRF8 gene to be associated at GWAS level with lcSSc (P = 2.32x10(-12), OR = 0.75). Also, rs12540874 in GRB10 gene (P = 1.27 x 10(-6), OR = 1.15) and rs11047102 in SOX5 gene (P = 1.39x10(-7), OR = 1.36) showed a suggestive association with lcSSc and ACA subgroups respectively. In the HLA region, we observed highly associated allelic combinations in the HLA-DQB1 locus with ACA (P = 1.79x10(-61), OR = 2.48), in the HLA-DPA1/B1 loci with ATA (P = 4.57x10(-76), OR = 8.84), and in NOTCH4 with ACA P = 8.84x10(-21), OR = 0.55) and ATA (P = 1.14x10(-8), OR = 0.54). We have identified three new non-HLA genes (IRF8, GRB10, and SOX5) associated with SSc clinical and auto-antibody subgroups. Within the HLA region, HLA-DQB1, HLA-DPA1/B1, and NOTCH4 associations with SSc are likely confined to specific auto-antibodies. These data emphasize the differential genetic components of subphenotypes of SSc

Sex-specific relevance of diabetes to occlusive vascular and other mortality: a collaborative meta-analysis of individual data from 980793 adults from 68 prospective studies

Background Several studies have shown that diabetes confers a higher relative risk of vascular mortality among women than among men, but whether this increased relative risk in women exists across age groups and within defined levels of other risk factors is uncertain. We aimed to determine whether differences in established risk factors, such as blood pressure, BMI, smoking, and cholesterol, explain the higher relative risks of vascular mortality among women than among men. Methods In our meta-analysis, we obtained individual participant-level data from studies included in the Prospective Studies Collaboration and the Asia Pacific Cohort Studies Collaboration that had obtained baseline information on age, sex, diabetes, total cholesterol, blood pressure, tobacco use, height, and weight. Data on causes of death were obtained from medical death certificates. We used Cox regression models to assess the relevance of diabetes (any type) to occlusive vascular mortality (ischaemic heart disease, ischaemic stroke, or other atherosclerotic deaths) by age, sex, and other major vascular risk factors, and to assess whether the associations of blood pressure, total cholesterol, and body-mass index (BMI) to occlusive vascular mortality are modified by diabetes. Results Individual participant-level data were analysed from 980 793 adults. During 9·8 million person-years of follow-up, among participants aged between 35 and 89 years, 19 686 (25·6%) of 76 965 deaths were attributed to occlusive vascular disease. After controlling for major vascular risk factors, diabetes roughly doubled occlusive vascular mortality risk among men (death rate ratio [RR] 2·10, 95% CI 1·97–2·24) and tripled risk among women (3·00, 2·71–3·33; χ2 test for heterogeneity p<0·0001). For both sexes combined, the occlusive vascular death RRs were higher in younger individuals (aged 35–59 years: 2·60, 2·30–2·94) than in older individuals (aged 70–89 years: 2·01, 1·85–2·19; p=0·0001 for trend across age groups), and, across age groups, the death RRs were higher among women than among men. Therefore, women aged 35–59 years had the highest death RR across all age and sex groups (5·55, 4·15–7·44). However, since underlying confounder-adjusted occlusive vascular mortality rates at any age were higher in men than in women, the adjusted absolute excess occlusive vascular mortality associated with diabetes was similar for men and women. At ages 35–59 years, the excess absolute risk was 0·05% (95% CI 0·03–0·07) per year in women compared with 0·08% (0·05–0·10) per year in men; the corresponding excess at ages 70–89 years was 1·08% (0·84–1·32) per year in women and 0·91% (0·77–1·05) per year in men. Total cholesterol, blood pressure, and BMI each showed continuous log-linear associations with occlusive vascular mortality that were similar among individuals with and without diabetes across both sexes. Interpretation Independent of other major vascular risk factors, diabetes substantially increased vascular risk in both men and women. Lifestyle changes to reduce smoking and obesity and use of cost-effective drugs that target major vascular risks (eg, statins and antihypertensive drugs) are important in both men and women with diabetes, but might not reduce the relative excess risk of occlusive vascular disease in women with diabetes, which remains unexplained. Funding UK Medical Research Council, British Heart Foundation, Cancer Research UK, European Union BIOMED programme, and National Institute on Aging (US National Institutes of Health)

Reactions of pulmonary emphysema patients before and after VRS - Forcusing on the rehabilitation, activity, surgery -

今まで内科的治療が主体であった肺気腫に対して,近年外科的治療(Volume Reduction Surgery 以後VRSと略す)が行われるようになった｡VRSを受ける患者の看護では,手術前後において, リハビリテーション(以後リハビリと略す)や機能回復に向けてのケアが必要不可欠とされる。そこで,本研究は肺気腫患者の適切な看護援助を検討するために,手術前後に示す肺気腫患者のリハビリや活動に対する反応を明らかにすることを目的とした｡対象者は当病棟に入院している肺気腫患者8名(VRS手術前8名,手術後はそのうちの6名である)で, リハビリ, 日常生活活動,呼吸,手術などについて,面接ならびに観察による調査を行った｡分析の結果,手術前においてリハビリでは≪義務感≫,頑張って行えば呼吸が楽になるという≪期待感≫,≪サポート≫,≪不安≫が,活動では≪活動の制限≫,手術では呼吸が楽になるのではという≪期待感≫,≪おまかせ≫,≪いちかばちかの賭け≫,≪不安≫,≪回復に向けての欲求の高まり≫が明らかになった｡手術後においてリハビリでは≪呼吸が楽になるための手段≫が, 日常生活活動では≪今の状態よりは良くなると いう期待感≫が,手術では≪達成感≫ と≪身体的苦痛≫が,将来については≪ささやかな欲求≫が明らかになった｡Pulmonary emphysema has been mainly treated with medicine, but recently VRS(volume reduction surgery) has been receiving much attention. In nursing care for VRS patients, it is important to help the patient improve his/her daily activities and recover physical function smoothly after surgery. The purpose of this study is to clarify the reactions of pulmonary emphysema patients before and after VRS for appropriate nursing. The subjects were eight pulmonary emphysema patients at a ward in Okayama University Hospital, but six of them completed both before and after VRS data collection. The data were collected by interview and observation, and from medical and nursing records. Contents of the interview included rehabilitation, daily activities, respiratory symptoms, operative stress, and so on. The results were as follows : , , , and on rehabilitation, on activity, , , , , and on surgery were extracted as pre-operative patients's reactions. on rehabilitation, on activity, and on surgery, on future were extracted as post-operative patients's reactions