Estimating health adjusted age at death (HAAD)

Objectives: At any point in time, a person’s lifetime health is the number of healthy life years they are expected to experience during their lifetime. In this article we propose an equity-relevant health metric, Health Adjusted Age at Death (HAAD), that facilitates comparison of lifetime health for individuals at the onset of different medical conditions, and allows for the assessment of which patient groups are worse off. A method for estimating HAAD is presented, and we use this method to rank four conditions in six countries according to several criteria of “worse off” as a proof of concept. Methods: For individuals with specific conditions HAAD consists of two components: past health (before disease onset) and future expected health (after disease onset). Four conditions (acute myeloid leukemia (AML), acute lymphoid leukemia (ALL), schizophrenia, and epilepsy) are analysed in six countries (Ethiopia, Haiti, China, Mexico, United States and Japan). Data from 2017 for all countries and for all diseases were obtained from the Global Burden of Disease Study database. In order to assess who are the worse off, we focus on four measures: the proportion of affected individuals who are expected to have HAAD<20 (T20), the 25th and 75th percentiles of HAAD for affected individuals (Q1 and Q3, respectively), and the average HAAD (aHAAD) across all affected individuals. Results: Even in settings where aHAAD is similar for two conditions, other measures may vary. One example is AML (aHAAD = 59.3, T20 = 2.0%, Q3-Q1 = 14.8) and ALL (58.4, T20 = 4.6%, Q3-Q1 = 21.8) in the US. Many illnesses, such as epilepsy, are associated with more lifetime health in high-income settings (Q1 in Japan = 59.2) than in low-income settings (Q1 in Ethiopia = 26.3). Conclusion: Using HAAD we may estimate the distribution of lifetime health of all individuals in a population, and this distribution can be incorporated as an equity consideration in setting priorities for health interventions.publishedVersio

New Creation instead of new Exodus : the innerbiblical exegesis and theological transformations of Isaiah 65:17–25

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Risk factor changes and mortality changes: A regional perspective on ischaemic heart disease in Norway 1966-1985

This study from Oppland county, Norway, examines risk factor changes in three regions with different mortality time trends among middle-aged males, for ischaemic heart disease, including sudden, unexpected death (IHD/SUD). The study is partly based on vital statistics and on results from two health screening surveys conducted in 1976-1978 and in 1981-1983. Regional data for the following risk factors are considered: serum cholesterol, systolic blood pressure, body weight and prevalence of smoking. Risk factor data are from the group of men aged 40-1949 years in 1976-1978. Changes in risk factor levels from 1976-1978 to 1981-1983 did not differ substantially between regions with widely different mortality time trends. The north-western, rural part of Oppland county experienced 80% IHD/SUD-mortality increase (95% confidence interval 35%-124%) from 1966-1970 to 1981-1985, among males aged 40-1959. The mean serum cholesterol level dropped by 1.7% (Pischaemic heart disease regional mortality risk factors males

Estimating health adjusted age at death (HAAD)

Objectives: At any point in time, a person’s lifetime health is the number of healthy life years they are expected to experience during their lifetime. In this article we propose an equity-relevant health metric, Health Adjusted Age at Death (HAAD), that facilitates comparison of lifetime health for individuals at the onset of different medical conditions, and allows for the assessment of which patient groups are worse off. A method for estimating HAAD is presented, and we use this method to rank four conditions in six countries according to several criteria of “worse off” as a proof of concept. Methods: For individuals with specific conditions HAAD consists of two components: past health (before disease onset) and future expected health (after disease onset). Four conditions (acute myeloid leukemia (AML), acute lymphoid leukemia (ALL), schizophrenia, and epilepsy) are analysed in six countries (Ethiopia, Haiti, China, Mexico, United States and Japan). Data from 2017 for all countries and for all diseases were obtained from the Global Burden of Disease Study database. In order to assess who are the worse off, we focus on four measures: the proportion of affected individuals who are expected to have HAAD<20 (T20), the 25th and 75th percentiles of HAAD for affected individuals (Q1 and Q3, respectively), and the average HAAD (aHAAD) across all affected individuals. Results: Even in settings where aHAAD is similar for two conditions, other measures may vary. One example is AML (aHAAD = 59.3, T20 = 2.0%, Q3-Q1 = 14.8) and ALL (58.4, T20 = 4.6%, Q3-Q1 = 21.8) in the US. Many illnesses, such as epilepsy, are associated with more lifetime health in high-income settings (Q1 in Japan = 59.2) than in low-income settings (Q1 in Ethiopia = 26.3). Conclusion: Using HAAD we may estimate the distribution of lifetime health of all individuals in a population, and this distribution can be incorporated as an equity consideration in setting priorities for health interventions

Baseline microvessel density predicts response to neoadjuvant bevacizumab treatment of locally advanced breast cancer

Abstract A subset of breast cancer patients benefits from preoperative bevacizumab and chemotherapy, but validated predictive biomarkers are lacking. Here, we aimed to evaluate tissue-based angiogenesis markers for potential predictive value regarding response to neoadjuvant bevacizumab treatment in breast cancer. In this randomized 1:1 phase II clinical trial, 132 patients with large or locally advanced HER2-negative tumors received chemotherapy ± bevacizumab. Dual Factor VIII/Ki-67 immunohistochemical staining was performed on core needle biopsies at baseline and week 12. Microvessel density (MVD), proliferative microvessel density (pMVD; Factor VIII/Ki-67 co-expression), glomeruloid microvascular proliferation (GMP), and a gene expression angiogenesis signature score, were studied in relation to pathologic complete response (pCR), clinico-pathologic features and intrinsic molecular subtype. We found that high baseline MVD (by median) significantly predicted pCR in the bevacizumab-arm (odds ratio 4.9, P  = 0.012). High pMVD, presence of GMP, and the angiogenesis signature score did not predict pCR, but were associated with basal-like ( P  ≤ 0.009) and triple negative phenotypes ( P  ≤ 0.041). pMVD and GMP did also associate with high-grade tumors ( P  ≤ 0.048). To conclude, high baseline MVD significantly predicted response to bevacizumab treatment. In contrast, pMVD, GMP, and the angiogenesis signature score, did not predict response, but associated with aggressive tumor features, including basal-like and triple-negative phenotypes

A PET/MRI study towards finding the optimal [18F]Fluciclovine PET protocol for detection and characterisation of primary prostate cancer.

Purpose: [18F]Fluciclovine PET imaging shows promise for the assessment of prostate cancer. The purpose of this PET/MRI study is to optimise the PET imaging protocol for detection and characterisation of primary prostate cancer, by quantitative evaluation of the dynamic uptake of [18F]Fluciclovine in cancerous and benign tissue. Methods: Patients diagnosed with high-risk primary prostate cancer underwent an integrated [18F]Fluciclovine PET/MRI exam before robot-assisted radical prostatectomy with extended pelvic lymph node dissection. Volumes-of-interest (VOIs) of selected organs (prostate, bladder, blood pool) and sub-glandular prostate structures (tumour, benign prostatic hyperplasia (BPH), inflammation, healthy tissue) were delineated on T2-weighted MR images, using whole-mount histology samples as a reference. Three candidate windows for optimal PET imaging were identified based on the dynamic curves of the mean and maximum standardised uptake value (SUVmean and SUVmax, respectively). The statistical significance of differences in SUV between VOIs were analysed using Wilcoxon rank sum tests (p<0.05, adjusted for multiple testing). Results: Twenty-eight (28) patients [median (range) age: 66 (55-72) years] were included. An early (W1: 5-10 minutes post-injection) and two late candidate windows (W2: 18-23; W3: 33-38 minutes post-injection) were selected. Late compared with early imaging was better able to distinguish between malignant and benign tissue [W3, SUVmean: tumour vs. BPH 2.5 vs. 2.0 (p<0.001), tumour vs. inflammation 2.5 vs. 1.7 (p<0.001), tumour vs. healthy tissue 2.5 vs. 2.0 (p<0.001); W1, SUVmean: tumour vs. BPH 3.1 vs. 3.1 (p=0.771), tumour vs inflammation 3.1 vs. 2.2 (p=0.021), tumour vs. healthy tissue 3.1 vs. 2.5 (p<0.001)] as well as between high-grade and low/intermediate-grade tumours (W3, SUVmean: 2.6 vs. 2.1 (p=0.040); W1, SUVmean: 3.1 vs. 2.8 (p=0.173)). These differences were relevant to the peripheral zone, but not the central gland. Conclusion: Late-window [18F]Fluciclovine PET imaging shows promise for distinguishing between prostate tumours and benign tissue and for assessment of tumour aggressiveness

Baseline microvessel density predicts response to neoadjuvant bevacizumab treatment of locally advanced breast cancer

A subset of breast cancer patients benefits from preoperative bevacizumab and chemotherapy, but validated predictive biomarkers are lacking. Here, we aimed to evaluate tissue-based angiogenesis markers for potential predictive value regarding response to neoadjuvant bevacizumab treatment in breast cancer. In this randomized 1:1 phase II clinical trial, 132 patients with large or locally advanced HER2-negative tumors received chemotherapy ± bevacizumab. Dual Factor VIII/Ki-67 immunohistochemical staining was performed on core needle biopsies at baseline and week 12. Microvessel density (MVD), proliferative microvessel density (pMVD; Factor VIII/Ki-67 co-expression), glomeruloid microvascular proliferation (GMP), and a gene expression angiogenesis signature score, were studied in relation to pathologic complete response (pCR), clinico-pathologic features and intrinsic molecular subtype. We found that high baseline MVD (by median) significantly predicted pCR in the bevacizumab-arm (odds ratio 4.9, P = 0.012). High pMVD, presence of GMP, and the angiogenesis signature score did not predict pCR, but were associated with basal-like (P ≤ 0.009) and triple negative phenotypes (P ≤ 0.041). pMVD and GMP did also associate with high-grade tumors (P ≤ 0.048). To conclude, high baseline MVD significantly predicted response to bevacizumab treatment. In contrast, pMVD, GMP, and the angiogenesis signature score, did not predict response, but associated with aggressive tumor features, including basal-like and triple-negative phenotypes

Combined 18F-Fluciclovine PET/MRI shows potential for detection and characterization of high-risk prostate cancer

The objective of this study is to investigate if quantitative imaging features derived from combined 18F-Fluciclovine Positron Emission Tomograpy (PET) / multiparametric Magnetic Resonance Imaging (MRI) show potential for detection and characterization of primary prostate cancer. Methods: Twenty-eight (28) patients diagnosed with high-risk prostate cancer underwent simultaneous 18F-Fluciclovine PET/MRI before radical prostatectomy. Volumes-of-interest (VOIs) of prostate tumors, benign prostatic hyperplasia (BPH) nodules, prostatitis, and healthy tissue were delineated on T2-weighted images using histology as a reference. Tumor VOIs were marked as high-grade (≥ Gleason Grade group 3) or not. MRI and PET features were extracted on the voxel and VOI-level. Partial least-squared discriminant analysis (PLS-DA) with double leave-one-patient-out cross validation was performed to classify tumor from benign tissue (BPH, prostatitis, healthy tissue) and high-grade tumor from other tissue (low-grade tumor, benign tissue). The performances of PET, MRI, and combined PET/MRI features were compared using the area under the receiver operating characteristic curve (AUC). Results: Voxel and VOI features were extracted from 40 tumor (26 high-grade), 36 BPH, 6 prostatitis, and 37 healthy tissue VOIs. PET/MRI performed better than MRI and PET for classification of tumor vs benign tissue (voxel: AUC 87%, 81%, and 83%; VOI: AUC 96%, 93%, and 93%, respectively) and high-grade tumor vs other tissue (voxel: AUC 85%, 79%, and 81%; VOI: AUC 93%, 93%, and 91%, respectively). T2-weighted MRI, diffusion-weighted MRI and PET features were most important for classification. Conclusion: Combined 18F-Fluciclovine PET/multiparametric MRI shows potential for improving detection and characterization of high-risk prostate cancer, in comparison to MRI and PET alone