Summary Procalcitonin is widely reported as a useful biochemical marker to differentiate sepsis from other non-infectious causes of systemic inflammatory response syndrome. In this systematic review, ...we estimated the diagnostic accuracy of procalcitonin in sepsis diagnosis in critically ill patients. 18 studies were included in the review. Overall, the diagnostic performance of procalcitonin was low, with mean values of both sensitivity and specificity being 71% (95% CI 67–76) and an area under the summary receiver operator characteristic curve of 0·78 (95% CI 0·73–0·83). Studies were grouped into phase 2 studies (n=14) and phase 3 studies (n=4) by use of Sackett and Haynes' classification. Phase 2 studies had a low pooled diagnostic odds ratio of 7·79 (95% CI 5·86–10·35). Phase 3 studies showed significant heterogeneity because of variability in sample size (meta-regression coefficient −0·592, p=0·017), with diagnostic performance upwardly biased in smaller studies, but moving towards a null effect in larger studies. Procalcitonin cannot reliably differentiate sepsis from other non-infectious causes of systemic inflammatory response syndrome in critically ill adult patients. The findings from this study do not lend support to the widespread use of the procalcitonin test in critical care settings.
BACKGROUND:The 5-level version of the EQ-5D (EQ-5D-5L) was introduced as an improvement on the original 3-level version (EQ-5D-3L). To date, 6 country-specific value sets have been published for ...EQ-5D-5L and 9 US value sets have been published for other instruments. Our aims were to (1) produce EQ-5D-5L values on a quality-adjusted life year (QALY) scale from the perspective of US adults and (2) compare them with US EQ-5D-3L values and the other country-specific EQ-5D-5L values.
METHODS:In 2016, 8222 US respondents from all 50 states and Washington, DC completed an online survey including a discrete choice experiment with 20 paired comparisons. Each comparison asked respondents, “Which do you prefer?” regarding a pair of alternatives described using EQ-5D-5L and lifespan attributes. On the basis of more than 50 choices on each of the 3160 pairs, we estimated EQ-5D-5L values on a QALY scale and compared them with the US EQ-5D-3L values and the other country-specific EQ-5D-5L values.
RESULTS:Ranging from −0.287 (55555) to 0.992 (11121) on a QALY scale, the estimated EQ-5D-5L values were similar to the US EQ-5D-3L values. Compared with the US EQ-5D-3L values, the values exhibited greater sensitivity and specificity and higher correlation with the EQ-5D-5L values of other countries, particularly England.
CONCLUSIONS:Like previous US valuation studies, this study produced nationally representative EQ-5D-5L values on a QALY scale. The results further demonstrate the advantages of the EQ-5D-5L over its 3-level predecessor as a preference-based summary measure of health-related quality of life from the perspective of US adults.
OBJECTIVE:Controversy remains as to whether low-dose corticosteroids can reduce the mortality and morbidity of acute lung injury (ALI) or the acute respiratory distress syndrome (ARDS) without ...increasing the risk of adverse reactions. We aimed to evaluate all studies investigating prolonged corticosteroids in low-to-moderate dose in ALI or ARDS.
DATA SOURCES:MEDLINE, EMBASE, Current Content, and Cochrane Central Register of Controlled Trials, and bibliographies of retrieved articles.
STUDY SELECTION:Randomized controlled trials (RCTs) and observational studies reported in any language that used 0.5–2.5 mg·kg·d of methylprednisolone or equivalent to treat ALI/ARDS.
DATA EXTRACTION:Data were extracted independently by two reviewers and included study design, patient characteristics, interventions, and mortality and morbidity outcomes.
DATA SYNTHESIS:Both cohort studies (five studies, n = 307) and RCTs (four trials, n = 341) showed a similar trend toward mortality reduction (RCTs relative risk 0.51, 95% CI 0.24–1.09; p = 0.08; cohort studies relative risk 0.66, 95% CI 0.43–1.02; p = 0.06). The overall relative risk was 0.62 (95% CI 0.43–0.91; p = 0.01). There was also improvement in length of ventilation-free days, length of intensive care unit stay, Multiple Organ Dysfunction Syndrome Score, Lung Injury Scores, and improvement in Pao2/Fio2. There was no increase in infection, neuromyopathy, or any major complications. There was significant heterogeneity in the pooled studies. Subgroup and meta-regression analyses showed that heterogeneity had minimal effect on treatment efficacy; however, these findings were limited by the small number of studies used in the analyses.
CONCLUSION:The use of low-dose corticosteroids was associated with improved mortality and morbidity outcomes without increased adverse reactions. The consistency of results in both study designs and all outcomes suggests that they are an effective treatment for ALI or ARDS. The mortality benefits in early ARDS should be confirmed by an adequately powered randomized trial.
Formative qualitative research is foundational to the methodological development process of quantitative health preference research (HPR). Despite its ability to improve the validity of the ...quantitative evidence, formative qualitative research is underreported.
To improve the frequency and quality of reporting, we developed guidelines for reporting this type of research. The guidelines focus on formative qualitative research used to develop robust and acceptable quantitative study protocols and corresponding survey instruments in HPR.
In December 2018, a steering committee was formed as a means to accumulate the expertise of the HPR community on the reporting guidelines (21 members, seven countries, multiple settings and disciplines). Using existing guidelines and examples, the committee constructed, revised, and refined the guidelines. The guidelines underwent beta testing by three researchers, and further revisions to the guidelines were made based on their feedback as well as on comments from members of the International Academy of Health Preference Research (IAHPR) and the editorial board of The Patient: Patient-Centered Outcomes Research.
The guidelines have five components: introductory material (4 domains), methods (12), results/findings (2), discussion (2), and other (2). They are concordant with existing guidelines, published examples, beta-testing results, and expert comments.
Publishing formative qualitative research is a necessary step toward strengthening the foundation of any quantitative study, enhancing the relevance of its preference evidence. The guidelines should aid researchers, reviewers, and regulatory agencies and promote transparency within HPR more broadly.
The Community Land Model (CLM) is the land component of the Community Earth System Model (CESM) and is used in several global and regional modeling systems. In this paper, we introduce model ...developments included in CLM version 5 (CLM5), which is the default land component for CESM2. We assess an ensemble of simulations, including prescribed and prognostic vegetation state, multiple forcing data sets, and CLM4, CLM4.5, and CLM5, against a range of metrics including from the International Land Model Benchmarking (ILAMBv2) package. CLM5 includes new and updated processes and parameterizations: (1) dynamic land units, (2) updated parameterizations and structure for hydrology and snow (spatially explicit soil depth, dry surface layer, revised groundwater scheme, revised canopy interception and canopy snow processes, updated fresh snow density, simple firn model, and Model for Scale Adaptive River Transport), (3) plant hydraulics and hydraulic redistribution, (4) revised nitrogen cycling (flexible leaf stoichiometry, leaf N optimization for photosynthesis, and carbon costs for plant nitrogen uptake), (5) global crop model with six crop types and time‐evolving irrigated areas and fertilization rates, (6) updated urban building energy, (7) carbon isotopes, and (8) updated stomatal physiology. New optional features include demographically structured dynamic vegetation model (Functionally Assembled Terrestrial Ecosystem Simulator), ozone damage to plants, and fire trace gas emissions coupling to the atmosphere. Conclusive establishment of improvement or degradation of individual variables or metrics is challenged by forcing uncertainty, parametric uncertainty, and model structural complexity, but the multivariate metrics presented here suggest a general broad improvement from CLM4 to CLM5.
Plain Language Summary
The Community Land Model (CLM) is the land component of the widely used Community Earth System Model (CESM). Here, we introduce model developments included in CLM version 5 (CLM5), the default land component for CESM2 which will be used for the Coupled Model Intercomparison Project (CMIP6). CLM5 includes many new and updated processes including (1) hydrology and snow features such as spatially explicit soil depth, canopy snow processes, a simple firn model, and a more mechanistic river model, (2) plant hydraulics and hydraulic redistribution, (3) revised nitrogen cycling with flexible leaf stoichiometry, leaf N optimization for photosynthesis, and carbon costs for plant nitrogen uptake, (4) expansion to six crop types (global) and time‐evolving irrigated areas and fertilization rates, (5) improved urban building energy model, and (6) carbon isotopes. New optional features include a demographically structured dynamic vegetation model, ozone damage to plants, and fire trace gas emissions coupling to the atmosphere. Model performance is generally improved for most assessed variables and metrics, though clear establishment of improvement or degradation is challenging due to model complexity as well as observational data limitations. Nonetheless, CLM5 is increasingly suited for research into a broad range of societally relevant scientific questions related to the terrestrial system.
Key Points
Updated Community Land Model has more hydrological and ecological process fidelity and more comprehensive representation of land management.
The model is systematically evaluated using International Land Model Benchmarking system and shows marked improvement over prior versions.
The myelodysplastic syndromes (MDSs) are hematologically diverse hematopoietic stem cell malignancies primarily affecting older individuals. The incidence of MDS in the United States is estimated at ...3.3 per 100 000; however, evidence suggests underreporting of MDS to centralized cancer registries. Contrary to clinical recommendations, registry guidelines from 2001-2010 required the capture of only one malignancy in the myeloid lineage and did not require blood count (BC) or bone marrow (BM) biopsy for MDS confirmation. To address these potential limitations, we constructed 4 claims-based algorithms to assess MDS incidence, applied the algorithms to the 2000-2008 Surveillance Epidemiology and End Results (SEER)–Medicare database, and assessed algorithm validity using SEER-registered MDS cases. Each algorithm required one or more MDS claims and accounted for recommended diagnostic services during the year before the first claim: 1+, 2+, 2 + BC, and 2 + BCBM (ordered by sensitivity). Each had moderate sensitivities (78.05%-92.90%) and high specificities (98.49%-99.84%), with the 2 + BCBM algorithm demonstrating the highest specificity. Based on the 2 + BCBM algorithm, the annual incidence of MDS is 75 per 100 000 persons 65 years or older—much higher than the 20 per 100 000 reported by SEER using the same sample.
Abstract Objective The European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) is one of the most commonly used measures in cancer care but in ...its current form cannot be used in economic evaluation because it does not incorporate preferences. We address this gap by estimating a preference-based measure for cancer from the EORTC QLQ-C30. Methods Factor analysis, Rasch analysis, and other psychometric analyses were undertaken on a clinical trial dataset of 655 patients with multiple myeloma to derive a health state classification system amenable to valuation. Second a valuation study was conducted of 350 members of the UK general population using time trade-off. Mean and individual-level multivariate regression models were fitted to derive preference weights for the classification system. Results The health state classification system has eight dimensions (physical functioning, role functioning, social functioning, emotional functioning, pain, fatigue and sleep disturbance, nausea, constipation, and diarrhea) with four or five levels each. Regression models have few inconsistencies (0 to 2) in estimated preference weights and small mean absolute error ranges (0.046 to 0.054). Conclusions It is feasible to derive a preference-based measure from the EORTC QLQ-C30 for use in economic evaluation. Future research will extend this to other countries and replicate across other patient groups.
The Spanish five-level EuroQol five-dimensional questionnaire (EQ-5D-5L) valuation study was the first to use the EuroQol Valuation Technology protocol, including composite time trade-off (C-TTO) and ...discrete choice experiments (DCE). In this study, its investigators noticed that some interviewers did not fully explain the C-TTO task to respondents. Evidence from a follow-up study in 2014 confirmed that when interviewers followed the protocol, the distribution of C-TTO responses widened.
To handle the data quality issues in the C-TTO responses by estimating a hybrid interval regression model to produce a Spanish EQ-5D-5L value set.
Four different models were tested. Model 0 integrated C-TTO and DCE responses in a hybrid model and models 1 to 3 altered the interpretation of the C-TTO responses: model 1 allowed for censoring of the C-TTO responses, whereas model 2 incorporated interval responses and model 3 included the interviewer-specific protocol violations. For external validation, the predictions of the four models were compared with those of the follow-up study using the Lin’s concordance correlation coefficient.
This stepwise approach to modeling C-TTO and DCE responses improved the concordance between the valuation and follow-up studies (concordance correlation coefficient: 0.948 model 0, 0.958 model 1, 0.952 model 2, and 0.989 model 3). We recommend the estimates from model 3, because its hybrid interval regression model addresses the data quality issues found in the valuation study.
Protocol violations may occur in any valuation study; handling them in the analysis can improve external validity. The resulting EQ-5D-5L value set (model 3) can be applied to inform Spanish health technology assessments.
Eroding permafrost coasts are likely indicators and integrators of changes in the Arctic System as they are susceptible to the combined effects of declining sea ice extent, increases in open water ...duration, more frequent and impactful storms, sea-level rise, and warming permafrost. However, few observation sites in the Arctic have yet to link decadal-scale erosion rates with changing environmental conditions due to temporal data gaps. This study increases the temporal fidelity of coastal permafrost bluff observations using near-annual high spatial resolution (<1 m) satellite imagery acquired between 2008-2017 for a 9 km segment of coastline at Drew Point, Beaufort Sea coast, Alaska. Our results show that mean annual erosion for the 2007-2016 decade was 17.2 m yr−1, which is 2.5 times faster than historic rates, indicating that bluff erosion at this site is likely responding to changes in the Arctic System. In spite of a sustained increase in decadal-scale mean annual erosion rates, mean open water season erosion varied from 6.7 m yr−1 in 2010 to more than 22.0 m yr−1 in 2007, 2012, and 2016. This variability provided a range of coastal responses through which we explored the different roles of potential environmental drivers. The lack of significant correlations between mean open water season erosion and the environmental variables compiled in this study indicates that we may not be adequately capturing the environmental forcing factors, that the system is conditioned by long-term transient effects or extreme weather events rather than annual variability, or that other not yet considered factors may be responsible for the increased erosion occurring at Drew Point. Our results highlight an increase in erosion at Drew Point in the 21st century as well as the complexities associated with unraveling the factors responsible for changing coastal permafrost bluffs in the Arctic.
Inhibition of sclerostin is a therapeutic approach to lowering fracture risk in patients with osteoporosis. However, data from phase 3 randomized controlled trials (RCTs) of romosozumab, a ...first-in-class monoclonal antibody that inhibits sclerostin, suggest an imbalance of serious cardiovascular events, and regulatory agencies have issued marketing authorizations with warnings of cardiovascular disease. Here, we meta-analyze published and unpublished cardiovascular outcome trial data of romosozumab and investigate whether genetic variants that mimic therapeutic inhibition of sclerostin are associated with higher risk of cardiovascular disease. Meta-analysis of up to three RCTs indicated a probable higher risk of cardiovascular events with romosozumab. Scaled to the equivalent dose of romosozumab (210 milligrams per month; 0.09 grams per square centimeter of higher bone mineral density), the
genetic variants were associated with lower risk of fracture and osteoporosis (commensurate with the therapeutic effect of romosozumab) and with a higher risk of myocardial infarction and/or coronary revascularization and major adverse cardiovascular events. The same variants were also associated with increased risk of type 2 diabetes mellitus and higher systolic blood pressure and central adiposity. Together, our findings indicate that inhibition of sclerostin may elevate cardiovascular risk, warranting a rigorous evaluation of the cardiovascular safety of romosozumab and other sclerostin inhibitors.
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