Summary Our objective was to determine international estimates of the economic burden of falls in older people living in the community. Our systematic review emphasized the need for a consensus on ...methodology for cost of falls studies to enable more accurate comparisons and subgroup-specific estimates among different countries. Introduction The purpose of this study was to determine international estimates of the economic burden of falls in older people living in the community. Methods This is a systematic review of peer-reviewed journal articles reporting estimates for the cost of falls in people aged ≥60 years living in the community. We searched for papers published between 1945 and December 2008 in MEDLINE, PUBMED, EMBASE, CINAHL, Cochrane Collaboration, and NHS EED databases that identified cost of falls in older adults. We extracted the cost of falls in the reported currency and converted them to US dollars at 2008 prices, cost items measured, perspective, time horizon, and sensitivity analysis. We assessed the quality of the studies using a selection of questions from Drummond's checklist. Results Seventeen studies met our inclusion criteria. Studies varied with respect to viewpoint of the analysis, definition of falls, identification of important and relevant cost items, and time horizon. Only two studies reported a sensitivity analysis and only four studies identified the viewpoint of their economic analysis. In the USA, non-fatal and fatal falls cost US $23.3 billion (2008 prices) annually and US $1.6 billion in the UK. Conclusions The economic cost of falls is likely greater than policy makers appreciate. The mean cost of falls was dependent on the denominator used and ranged from US $3,476 per faller to US $10,749 per injurious fall and US $26,483 per fall requiring hospitalization. A consensus on methodology for cost of falls studies would enable more accurate comparisons and subgroup-specific estimates among different countries.
Background. Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) can show variable clinical trajectories. Previous longitudinal studies of HAND typically have been brief, did ...not use adequate normative standards, or were conducted in the context of a clinical trial, thereby limiting our understanding of incident neurocognitive (NC) decline and recovery. Methods. We investigated the incidence and predictors of NC change over 16–72 (mean, 35) months in 436 HIV-infected participants in the CNS HIV Anti-Retroviral Therapy Effects Research Cohort. Comprehensive laboratory, neuromedical, and NC assessments were obtained every 6 months. Published, regression-based norms for NC change were used to generate overall change status (decline vs stable vs improved) at each study visit. Survival analysis was used to examine the predictors of time to NC change. Results. Ninety-nine participants (22.7%) declined, 265 (60.8%) remained stable, and 72 (16.5%) improved. In multivariable analyses, predictors of NC improvements or declines included time-dependent treatment status and indicators of disease severity (current hematocrit, albumin, total protein, aspartate aminotransferase), and baseline demographics and estimated premorbid intelligence quotient, non-HIV-related comorbidities, current depressive symptoms, and lifetime psychiatric diagnoses (overall model P < .0001). Conclusions. NC change is common in HIV infection and appears to be driven by a complex set of risk factors involving HIV disease, its treatment, and comorbid conditions.
This is a cross-sectional, observational study to determine the frequency and associated features of HIV-associated neurocognitive disorders (HAND) in a large, diverse sample of infected individuals ...in the era of combination antiretroviral therapy (CART).
A total of 1,555 HIV-infected adults were recruited from 6 university clinics across the United States, with minimal exclusions. We used standardized neuromedical, psychiatric, and neuropsychological (NP) examinations, and recently published criteria for diagnosing HAND and classifying 3 levels of comorbidity (minimal to severe non-HIV risks for NP impairment).
Fifty-two percent of the total sample had NP impairment, with higher rates in groups with greater comorbidity burden (40%, 59%, and 83%). Prevalence estimates for specific HAND diagnoses (excluding severely confounded cases) were 33% for asymptomatic neurocognitive impairment, 12% for mild neurocognitive disorder, and only 2% for HIV-associated dementia (HAD). Among participants with minimal comorbidities (n = 843), history of low nadir CD4 was a strong predictor of impairment, and the lowest impairment rate on CART occurred in the subset with suppressed plasma viral loads and nadir CD4 ≥200 cells/mm(3) (30% vs 47% in remaining subgroups).
The most severe HAND diagnosis (HAD) was rare, but milder forms of impairment remained common, even among those receiving CART who had minimal comorbidities. Future studies should clarify whether early disease events (e.g., profound CD4 decline) may trigger chronic CNS changes, and whether early CART prevents or reverses these changes.
In 1991, the AIDS Task Force of the American Academy of Neurology published nomenclature and research case definitions to guide the diagnosis of neurologic manifestations of HIV-1 infection. Now, 16 ...years later, the National Institute of Mental Health and the National Institute of Neurological Diseases and Stroke have charged a working group to critically review the adequacy and utility of these definitional criteria and to identify aspects that require updating. This report represents a majority view, and unanimity was not reached on all points. It reviews our collective experience with HIV-associated neurocognitive disorders (HAND), particularly since the advent of highly active antiretroviral treatment, and their definitional criteria; discusses the impact of comorbidities; and suggests inclusion of the term asymptomatic neurocognitive impairment to categorize individuals with subclinical impairment. An algorithm is proposed to assist in standardized diagnostic classification of HAND.
Studies of targeted therapy resistance in lung cancer have primarily focused on single-gene alterations. Based on prior work implicating apolipoprotein b mRNA-editing enzyme, catalytic ...polypeptide-like (APOBEC) mutagenesis in histological transformation of epidermal growth factor receptor (EGFR)-mutant lung cancers, we hypothesized that mutational signature analysis may help elucidate acquired resistance to targeted therapies.
APOBEC mutational signatures derived from an Food and Drug Administration-cleared multigene panel Memorial Sloan Kettering Cancer Center Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) using the Signature Multivariate Analysis (SigMA) algorithm were validated against the gold standard of mutational signatures derived from whole-exome sequencing. Mutational signatures were decomposed in 3276 unique lung adenocarcinomas (LUADs), including 93 paired osimertinib-naïve and -resistant EGFR-mutant tumors. Associations between APOBEC and mechanisms of resistance to osimertinib were investigated. Whole-genome sequencing was carried out on available EGFR-mutant lung cancer samples (10 paired, 17 unpaired) to investigate large-scale genomic alterations potentially contributing to osimertinib resistance.
APOBEC mutational signatures were more frequent in receptor tyrosine kinase (RTK)-driven lung cancers (EGFR, ALK, RET, and ROS1; 25%) compared to LUADs at large (20%, P < 0.001); across all subtypes, APOBEC mutational signatures were enriched in subclonal mutations (P < 0.001). In EGFR-mutant lung cancers, osimertinib-resistant samples more frequently displayed an APOBEC-dominant mutational signature compared to osimertinib-naïve samples (28% versus 14%, P = 0.03). Specifically, mutations detected in osimertinib-resistant tumors but not in pre-treatment samples significantly more frequently displayed an APOBEC-dominant mutational signature (44% versus 23%, P < 0.001). EGFR-mutant samples with APOBEC-dominant signatures had enrichment of large-scale genomic rearrangements (P = 0.01) and kataegis (P = 0.03) in areas of APOBEC mutagenesis.
APOBEC mutational signatures are frequent in RTK-driven LUADs and increase under the selective pressure of osimertinib in EGFR-mutant lung cancer. APOBEC mutational signature enrichment in subclonal mutations, private mutations acquired after osimertinib treatment, and areas of large-scale genomic rearrangements highlights a potentially fundamental role for APOBEC mutagenesis in the development of resistance to targeted therapies, which may be potentially exploited to overcome such resistance.
•RTK-driven lung cancers display higher levels of APOBEC mutagenesis as compared to other lung cancers.•RTK-driven LUAD with evidence of APOBEC mutagenesis are enriched in subclonal mutations.•APOBEC is a dominant mutational process in post-osimertinib samples of EGFR-mutant lung cancers.•APOBEC mutagenesis might have a relevant role in the development of resistance to targeted therapies.
Summary
We estimated the incremental cost-effectiveness of a once-weekly or twice-weekly resistance training intervention compared with balance and tone classes in terms of falls prevented and ...quality-adjusted life years (QALYs) gained. Both resistance training interventions were more likely to save health care resource money and offer better health outcomes for falls prevention than balance and tone classes.
Introduction
This study aims to estimate the incremental cost-effectiveness and cost-utility of a once-weekly or twice-weekly resistance training intervention compared with twice-weekly balance and tone classes in terms of falls prevented and QALYs gained.
Methods
Economic evaluation was conducted concurrently with a three-arm randomized controlled trial including 155 community-dwelling women aged 65 to 75 years, Mini Mental State Examination ≥24, and visual acuity 20/40 or better. Participants received the once-weekly resistance training (
n
= 54), the twice-weekly resistance training (
n
= 51) or the twice-weekly balance and tone (the comparator) classes (
n
= 50) for 1 year. Measurements included the number of falls for each participant, healthcare resource utilization, and associated costs over 9 months; health status was assessed using the EQ-5D and SF-6D to calculate QALYs.
Results
Based on the point estimates from our base case analysis, we found that both once- and twice-weekly resistance training groups were less costly (
p
< 0.05) and more effective than twice-weekly balance and tone classes. The incremental QALYs assessed using the SF-6D were 0.003 for both the once- and twice-weekly resistance training groups, compared with the twice-weekly balance and tone classes. The incremental QALYs assessed using the EQ-5D were 0.084 for the once-weekly and 0.179 for the twice-weekly resistance training groups, respectively, compared with the twice-weekly balance and tone classes.
Conclusions
An individually tailored resistance training intervention delivered once or twice weekly provided better value for money for falls prevention than balance and tone classes.
Old-growth forests are subject to substantial changes in structure and species composition due to the intensification of human activities, gradual climate change and extreme weather events. Trees ...store ca. 90 % of the total aboveground biomass (AGB) in tropical forests and precise tree biomass estimation models are crucial for management and conservation. In the central Amazon, predicting AGB at large spatial scales is a challenging task due to the heterogeneity of successional stages, high tree species diversity and inherent variations in tree allometry and architecture. We parameterized generic AGB estimation models applicable across species and a wide range of structural and compositional variation related to species sorting into height layers as well as frequent natural disturbances. We used 727 trees (diameter at breast height ≥ 5 cm) from 101 genera and at least 135 species harvested in a contiguous forest near Manaus, Brazil. Sampling from this data set we assembled six scenarios designed to span existing gradients in floristic composition and size distribution in order to select models that best predict AGB at the landscape level across successional gradients. We found that good individual tree model fits do not necessarily translate into reliable predictions of AGB at the landscape level. When predicting AGB (dry mass) over scenarios using our different models and an available pantropical model, we observed systematic biases ranging from −31 % (pantropical) to +39 %, with root-mean-square error (RMSE) values of up to 130 Mg ha−1 (pantropical). Our first and second best models had both low mean biases (0.8 and 3.9 %, respectively) and RMSE (9.4 and 18.6 Mg ha−1) when applied over scenarios. Predicting biomass correctly at the landscape level in hyperdiverse and structurally complex tropical forests, especially allowing good performance at the margins of data availability for model construction/calibration, requires the inclusion of predictors that express inherent variations in species architecture. The model of interest should comprise the floristic composition and size-distribution variability of the target forest, implying that even generic global or pantropical biomass estimation models can lead to strong biases. Reliable biomass assessments for the Amazon basin (i.e., secondary forests) still depend on the collection of allometric data at the local/regional scale and forest inventories including species-specific attributes, which are often unavailable or estimated imprecisely in most regions.
A Review on solid oxide fuel cell models Wang, K.; Hissel, D.; Péra, M.C. ...
International journal of hydrogen energy,
06/2011, Volume:
36, Issue:
12
Journal Article
Peer reviewed
Since the model plays an important role in diagnosing solid oxide fuel cell (SOFC) system, this paper proposes a review of existing SOFC models for model-based diagnosis of SOFC stack and system. ...Three categories of modelling based on the white-, the black- and the grey-box approaches are introduced. The white-box model includes two types, i.e. physical model and equivalent circuit model based on EIS technique. The black-box model is based on artificial intelligence and its realisation relies mainly on experimental data. The grey-box model is more flexible: it is a physical representation but with some parts being modelled empirically. Validation of models is discussed and a hierarchical modelling approach involving all of three modelling methods is briefly mentioned, which gives an overview of the design for implementing a generic diagnostic tool on SOFC system.
Summary Objective To examine the relationship of knee malalignment with occurrence of incident and enlarging bone marrow lesions (BMLs) and regression of BMLs. Methods Subjects from the Multicenter ...Osteoarthritis Study aged 50–79 years with or at high risk of knee osteoarthritis were studied. Full-limb radiographs were taken at baseline and hip–knee–ankle mechanical axis was measured. Baseline and 30-month magnetic resonance imaging (MRI) of knees ( n = 1782) were semiquantitatively assessed for BMLs. Outcome was defined as a change in BML score in femoral/tibial condyle in medial/lateral compartments. Medial compartment in varus alignment and lateral compartment in valgus alignment were combined to form ‘more loaded’ compartment, while lateral compartment in valgus and medial compartment in varus were combined to form ‘less loaded’ compartment. Relative risk (RR) of BML score increase or decrease in relation to malalignment was estimated using a log linear regression model with the Poisson assumption, adjusting for age, gender, body mass index, physical activity scale for the elderly, race and clinic site. Further, results were stratified by ipsilateral meniscal and cartilage status at baseline. Results Baseline varus alignment was associated with higher risk of BML score increase from baseline to follow-up in the medial compartment adjusted RRs (95%CI): 1.5 (1.2–1.9) and valgus alignment in the lateral compartment 1.4 (1.0–2.1). Increase in BML score was more likely in the more loaded compartments 1.7 (1.4–2.0) in malaligned knees. Regardless of ipsilateral cartilage or meniscus status, adjusted RR for BML score increase was higher in the more loaded compartments of malaligned knees than those with neutral alignment. Decrease in BML score was less likely in the more loaded compartments in malaligned knees 0.8 (0.7–1.0). Conclusion Knee malalignment is associated with increased risk of incident and enlarging BMLs in the more loaded compartments of the tibiofemoral joint.
ObjectiveTo define clinical and laboratory features that identify patients with neurosyphilis MethodsSubjects (n=326) with syphilis but no previous neurosyphilis who met 1993 Centers for Disease ...Control and Prevention criteria for lumbar puncture underwent standardized history, neurological examination, venipuncture, and lumbar puncture. Neurosyphilis was defined as a cerebrospinal fluid (CSF) white blood cell count >20 cells/μL or reactive CSF Venereal Disease Research Laboratory (VDRL) test result ResultsSixty-five subjects (20.1%) had neurosyphilis. Early syphilis increased the odds of neurosyphilis in univariate but not multivariate analyses. In multivariate analyses, serum rapid plasma reagin (RPR) titer ⩾1:32 increased the odds of neurosyphilis 10.85-fold in human immunodeficiency virus (HIV)–uninfected subjects and 5.98-fold in HIV-infected subjects. A peripheral blood CD4+ T cell count ⩽350 cells/μL conferred 3.10-fold increased odds of neurosyphilis in HIV-infected subjects. Similar results were obtained when neurosyphilis was more stringently defined as a reactive CSF VDRL test result ConclusionSerum RPR titer helps predict the likelihood of neurosyphilis. HIV-induced immune impairment may increase the risk of neurosyphilis
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