Stratification Variables Research Articles

Emergency Department Utilization By Hemophilia Patients in United States

INTRODUCTIONPatients with hemophilia are prone to life threatening bleeds and central line associated morbidities. It is pivotal that emergency departments (ED) are both equipped and trained to address these complications with acuity. The purpose of this study is to determine the utilization of ED for hemophilia related complaints. METHODSRetrospective review of information collected from the National Emergency Department Database Sample (NEDS) was performed. The NEDS is a stratified sample of hospital-based ED visits and publically available for purchase as a component of the Healthcare Cost and Utilization Project. We are presenting the results of comparative analysis and frequencies computed from the database.The ED visits with hemophilia, listed as one of the diagnoses, were selected. Patient demographics and hospital stratification variables were recorded. A snapshot of these variables from years 2006 to 2013 was obtained but due to large sample size, we elected to perform detailed analysis on data from the year 2012. Hospital charges and other variables were computed from the database and projected to national levels using the discharge weighted variables. Study was funded by "Bayer Healthcare, Investigator Initiated Research Grant". RESULTSDuring the 8 years period studied, ~163,000 ED visits were made by hemophilia patients. This represented 0.016% of total visits to EDs nationwide. The two age groups that were most likely to utilize ED were children under 18 years and adults under 45 years (37% each). More than half of these patients resided in large metropolitan cities or their suburbs. Interestingly 20% of patients had annual household income greater than $63,000. Although Medicaid and Medicare were the largest primary payers (54%), 30% had private insurance listed as primary payer. About 45% of the ED visits were at a non-teaching hospital. As a snap shot of frequencies the trends in above mentioned results had remained unchanged from 2006 to 2013.Detailed analysis of the purchased database for the year 2012 was performed. Out of 31 million ED visits in the year 2012; 4,488 visits were made by patients with hemophilia and 84% of them had hemophilia A (Sample representing 20% of target universe). Mean age at presentation was 29 years. There was not a significant difference in the number of ED visits among different months of the year or days of the week. Most visits were made in June (358) and least visits during February (294). Average charge per visit was $4,000; the highest charge for a single ED visit was $150,000. National estimate of total charges for ED visits by patients with hemophilia in the year 2012 was over 60 million dollars. Average charge for ED visits at a private hospital was $2,988 compared to $2,254 at a public hospital (p=0.03). The cost of ED utilization by lower income group patients was greater than patients from higher income group; however the difference in average charges was not statistically significant.There were over 21,000 diagnoses codes recorded during 4,488 ED visits by hemophilia patients. Cardiovascular complaints (n=2060) were the most frequently reported, followed by injuries and poisoning (n=2038). Hemorrhage was the presenting complaint 32% (n=1452) of times. The breakdown of bleeds included 682 contusions, 317 hemarthrosis, 163 gastrointestinal bleeds, 96 hematuria, 83 epistaxis, 47 intracranial bleeds and 18 menstrual bleeds. Injuries were reported as primary diagnosis, 26% of times. Septicemia was diagnosed during 147 visits. Around 70% of patients were treated and released from the ED. Two patients reportedly died in the ED while 35 died after being admitted to the hospital. Cause of death included Sepsis and brain hemorrhage in 26 and 4 patients respectively. In pediatric patients only, injuries were the most frequent complaints (n=870) followed by joint and soft tissue disorders (n=366); fever (n=92) and central line complications (n=63). CONCLUSIONHemophilia is a rare hematologic disease but patients with hemophilia have a high tendency to utilize ED. Proper education of patients and ED staff could help reduce the economic burden and ensure optimum care delivery in the ED. To our knowledge this is the first study to analyze ED utilization by hemophilia patients from a national database. Based on our study results, patients were evenly distributed in low and high income groups and utilized teaching and non-teaching hospital EDs alike. DisclosuresZakieh:Bayer Healthcare Investigator Initiated research Grant: Research Funding. Al-Ghafry:Bayer Healthcare Investigator Initiated research Grant: Research Funding. Siddiqui:Bayer Healthcare Investigator Initiated research Grant: Research Funding.

Effects of sodium thiosulfate versus observation on development of cisplatin-induced hearing loss in children with cancer (ACCL0431): a multicentre, randomised, controlled, open-label, phase 3 trial

Sodium thiosulfate is an antioxidant shown in preclinical studies in animals to prevent cisplatin-induced hearing loss with timed administration after cisplatin without compromising the antitumour efficacy of cisplatin. The primary aim of this study was to assess sodium thiosulfate for prevention of cisplatin-induced hearing loss in children and adolescents. ACCL0431 was a multicentre, randomised, open-label, phase 3 trial that enrolled participants at 38 participating Children's Oncology Group hospitals in the USA and Canada. Eligible participants aged 1-18 years with newly diagnosed cancer and normal audiometry were randomly assigned (1:1) to receive sodium thiosulfate or observation (control group) in addition to their planned cisplatin-containing chemotherapy regimen, using permuted blocks of four. Randomisation was initially stratified by age and duration of cisplatin infusion. Stratification by previous cranial irradiation was added later as a protocol amendment. The allocation sequence was computer-generated centrally and concealed to all personnel. Participants received sodium thiosulfate 16 g/m2 intravenously 6 h after each cisplatin dose or observation. The primary endpoint was incidence of hearing loss 4 weeks after final cisplatin dose. Hearing was measured using standard audiometry and reviewed centrally by audiologists masked to allocation using American Speech-Language-Hearing Association criteria but treatment was not masked for participants or clinicians. Analysis of the primary endpoint was by modified intention to treat, which included all randomly assigned patients irrespective of treatment received but restricted to those assessable for hearing loss. Enrolment is complete and this report represents the final analysis. This trial is registered with ClinicalTrials.gov, number NCT00716976. Between June 23, 2008, and Sept 28, 2012, 125 eligible participants were randomly assigned to either sodium thiosulfate (n=61) or observation (n=64). Of these, 104 participants were assessable for the primary endpoint (sodium thiosulfate, n=49; control, n=55). Hearing loss was identified in 14 (28·6%; 95% CI 16·6-43·3) participants in the sodium thiosulfate group compared with 31 (56·4%; 42·3-69·7) in the control group (p=0·00022). Adjusted for stratification variables, the likelihood of hearing loss was significantly lower in the sodium thiosulfate group compared with the control group (odds ratio 0·31, 95% CI 0·13-0·73; p=0·0036). The most common grade 3-4 haematological adverse events reported, irrespective of attribution, were neutropenia (117 [66%] of 177 participant cycles in the sodium thiosulfate group vs 145 [65%] of 223 in the control group), whereas the most common non-haematological adverse event was hypokalaemia (25 [17%] of 147 vs 22 [12%] of 187). Of 194 serious adverse events reported in 26 participants who had received sodium thiosulfate, none were deemed probably or definitely related to sodium thiosulfate; the most common serious adverse event was decreased neutrophil count: 26 episodes in 14 participants. Sodium thiosulfate protects against cisplatin-induced hearing loss in children and is not associated with serious adverse events attributed to its use. Further research is needed to define the appropriate role for sodium thiosulfate among emerging otoprotection strategies. US National Cancer Institute.

From Euclidean distances to APC models

In this paper we show that a recently developed method for the study of “cultural” differences, called DBS-EM, or Distance Between Strata estimated with the EM (Expectation Maximization) algorithm, can also be used to circumvent the difficulties posed by APC (or Age, Period, Cohort) models. The DBS-EM method produces an original measure of the distance (dependent variable) between any two subsets of observations (strata) within a sample, where the stratification variables can be interpreted as regressors. When these stratification variables are age, period, and cohort, what results is an APC model which, however, proves immune to the “intrinsic collinearity problem” (C = P−A). With a few limitations, to be sure, which are discussed in the article. In our application to Italian data over the years 1993–2013, age and cohort strongly shape cultural consumption, while cohort and period impact, but only up to a point, on political participation.

Collaborative Assessment and Management of Suicidality (CAMS) compared to treatment as usual (TAU) for suicidal patients: study protocol for a randomized controlled trial.

BackgroundCollaborative Assessment and Management of Suicidality (CAMS) is a therapeutic framework that appears promising to reduce suicidal ideation and suicidal cognition. CAMS has not previously been evaluated in a standard specialized mental health care setting for patients with suicidal problems in general. In this pragmatic randomized controlled trial (RCT) we will investigate if CAMS is more effective than treatment as usual (TAU) in reducing suicidal thoughts and behaviors. Effects will also be investigated on mental health and symptom relief in general and upon readmissions to inpatient units.Methods/designThe study is a multicenter, observer-blinded, superiority, two-armed RCT which will include patients from four clinical departments at Vestre Viken Hospital Trust, Norway. We aim to include 100 patients with moderate to strong suicidal problems, as defined by a score of 13 or more on Beck’s Scale for Suicide Ideation - Current. Patients are included regardless of diagnosis. Randomization will be performed using a stratified four-block procedure with treatment unit as the stratification variable. The duration of treatment will vary depending on patients’ needs and clinical assessments. Patients are interviewed by research staff at four checkpoints: baseline, 2 weeks, 6 months, and 12 months. Central outcome measures are the Beck Scale for Suicide Ideation - Current, Outcome Questionnaire – 45, and Suicide Attempt Self-Injury Count.DiscussionThis pragmatic trial is effectuated within the Public Health Care System in Norway, where patients have multiple problems and diagnoses and therapists have a high work load. Results from this trial are highly generalizable to a typical everyday clinical setting, and one should expect similar results if CAMS is implemented in the future as a standard component in specialized mental health care systems.Trial registrationOpen Science Framework: DOI 10.17605/OSF.IO/JHRM2. Registered 5 July 2015. ClinicalTrials.gov: NCT02685943. Registered on 8 February 2016.

Dietary vitamin C intake protects against COPD: the Korea National Health and Nutrition Examination Survey in 2012.

BackgroundVitamin C, as an antioxidant, has recently been suggested to provide protection against COPD; however, only few national cohort studies have investigated these effects. We aimed to confirm the protective effects of vitamin C against COPD in Korean patients.Patients and methodsWe analyzed the data of 3,283 adults aged ≥40 years (representing 23,541,704 subjects) who underwent pulmonary function tests and responded to questionnaires on smoking history and vitamin C intake, with stratification variables and sampling weight designated by the Korea 2012 National Health and Nutrition Examination Survey.ResultsAmong all the subjects, 512 (representing 3,459,679 subjects; 15.6%) were diagnosed as having COPD based on pulmonary function test results. Male gender, old age, residence in suburban/rural regions, low household income, low educational level, an occupation in agriculture or fisheries, and heavy smoking were significantly associated with COPD. Low intake of nutrients, including potassium, vitamin A, carotene, retinol, and vitamin C, was significantly associated with COPD. The prevalence of COPD in heavy smokers with the lowest quartile (Q1, <48.50 mg; 63.0%) and low-middle quartile (Q2, 48.50−84.38 mg; 56.4%) of vitamin C intake was significantly higher than that in subjects with the high-middle quartile (Q3, 84.38−141.63 mg; 29.5%) and highest quartile (Q4, >141.63 mg; 32.6%) of vitamin C intake (P=0.015). In multivariate analysis, male gender, old age, heavy smoking, and a low intake of vitamin C were significant independent risk factors for COPD. A significant reduction of 76.7% in COPD risk was observed with a Q3 vitamin C intake compared to Q1 vitamin C intake (odds ratio, 0.233; 95% confidence interval, 0.094−0.576) in heavy smokers.ConclusionThis large-scale national study suggests that dietary vitamin C provides protection against COPD, independent of smoking history, in the general Korean population.

Is subvalvular repair worthwhile in severe ischemic mitral regurgitation? Subanalysis of the Papillary Muscle Approximation trial

ObjectiveThe symmetry of mitral valve tethering and regional left ventricle wall dysfunction are reported to play a fundamental role in the outcomes and long-term durability of surgical repair in ischemic mitral regurgitation (IMR). We recently demonstrated in a randomized clinical trial (the Papillary Muscle Approximation trial) the superiority of papillary muscle approximation (PMA) in combination with standard restrictive annuloplasty (RA) in severe IMR over annuloplasty alone in terms of adverse left ventricular remodeling and mitral regurgitation (MR) recurrence. This approach, however, failed to produce a survival advantage and was still plagued by a high incidence of reoperation. We therefore performed a subanalysis of the PMA trial on the basis of preoperative parameters to elucidate the value of subvalvular surgery in certain subcategories of patients with the aim of creating a decisional algorithm on the best operative strategy. MethodsWe performed a subanalysis of PMA trial, evaluating 96 patients with severe IMR and eligible for myocardial revascularization randomized to PMA + RA (n = 48) versus RA alone (n = 48) in association with coronary artery bypass grafting. Endpoints included left ventricular remodeling, MR recurrence, overall mortality, reoperation, and a composite cardiac endpoint (cardiac death, stroke, reintervention, hospitalization for heart failure, or New York Heart Association class worsening). Stratification variables were preoperative symmetry of mitral valve tethering and regional wall motion abnormality. ResultsPMA improved ventricular remodeling and recurrence of MR in both preoperative symmetric and asymmetric tethering and in case of inferior wall dyskinesia but did not produce an additional benefit in anterolateral wall dysfunction. ConclusionsPreoperative symmetric and asymmetric tethering and isolated inferior wall dyskinesia are an indication for subvalvular apparatus surgery in IMR.

Processes and factors influencing the through-flow of new deepwater in the Bornholm Basin

Summary This paper is based on the idea that the hydrographical conditions in the Bornholm Basin, and any other basin, can be understood from knowledge of general hydromechanical principles and basin-specific factors. Published results on the variability of the vertical stratification are shown and discussed. Such analyses demonstrate the residence time of water at different depth levels. Different modes of currents forced by winds and by stratification gradients at open vertical boundaries are presented. Vertical mixing is discussed and published results for the Bornholm Basin are shown. An experiment demonstrates that the diffusive properties of the enclosed basin, i.e. below the sill depth of the Slupsk Furrow, can be computed quite well from the horizontal mean vertical diffusivity obtained from historical hydrographical observations. A published two decades long simulation of the vertical stratification shows that the through flow and modification of new deepwater in the Bornholm Basin can be well described based on existing knowledge regarding crucial hydromechanical processes. It also suggests, indirectly, that there should be a weak anticyclonic circulation above the sill depth, which is supported by current measurements.

The Traumatic Injuries Distress Scale: A New Tool That Quantifies Distress and Has Predictive Validity With Patient-Reported Outcomes

Study Design Observational cohort. Background Outcomes for acute musculoskeletal injuries are currently suboptimal, with an estimated 10% to 50% of injured individuals reporting persistent problems. An early risk-targeted intervention may hold value for improving outcomes. Objectives To describe the development and preliminary concurrent and longitudinal validation of the Traumatic Injuries Distress Scale (TIDS), a new tool intended to provide the magnitude and nature of risk for persistent problems following acute musculoskeletal injuries. Methods Two hundred participants recruited from emergency medicine departments and rehabilitation clinics completed the TIDS and a battery of other self-reported questionnaires. A subcohort (n = 76) was followed at 1 week and at 12 weeks after the inciting event. Exploratory factor analysis and concurrent and longitudinal correlations were used to evaluate the ability of the TIDS to predict acute presentation and 12-week outcomes. Results Exploratory factor analysis revealed 3 factors explaining 62.8% of total scale variance. Concurrent and longitudinal associations with established clinical measures supported the nature of each subscale. Scores on the TIDS at baseline were significantly associated with variability in disability, pain intensity, satisfaction, anxiety, and depression at 12 weeks postinjury, with adequate accuracy to endorse its use as part of a broader screening protocol. Limitations to interpretation are discussed. Conclusion We present the initial psychometric properties of a new measure of acute posttraumatic distress following musculoskeletal injury. The subscales may be useful as stratification variables in subsequent investigations of clinical interventions. J Orthop Sports Phys Ther 2016;46(10):920-928. Epub 3 Sep 2016. doi:10.2519/jospt.2016.6594.

The statistical structure of synoptic variability ocean currents at the continental slope of the Laptev Sea and features of their generation by anemobaric forces

Based on vector-algebraic analysis of random processes, we study the statistical structure of the synoptic variability of currents measured by an ADCP in the upper mixed layer in the central part of the continental slope of the Laptev Sea in 2006–2007. The results of statistical analysis show that in some cases the synoptic currents in the surface layer of the sea are signs of wind drift currents. This is indicated by the high correlation between the tangential friction of wind and currents, as well as the reversal of the depth of current vectors and the major axes of the ellipses of the mean-square deviation of the Ekman spiral. Due to the large variability of wind flows and stratification of water masses, the penetration depth of these currents is small and varies from 6 to 30 m, with pronounced seasonal variation. In deeper layers, no relationship between the currents and anemobaric forces is traced. It is concluded that the fluctuations of synoptic scale currents in the area of the continental slope of the Laptev Sea represent a superposition of Ekman drift currents and movements associated with free baroclinic Kelvin waves. These currents are the dominant contributor in the upper 30-m layer of the ocean, while waves play a key role in deeper waters.

Progression from normal cognition to mild cognitive impairment in a diverse clinic-based and community-based elderly cohort

IntroductionInvestigation of the conversion rates from normal cognition (NC) to mild cognitive impairment (MCI) is important, as effective early intervention could potentially prevent or substantially delay the onset of dementia. However, reported conversion rates differ across studies and recruitment source. Our study examined predictors of conversion from NC to MCI in a racially and ethnically diverse sample drawn both from community and clinic recruitment sources. MethodsRates and predictors of conversion were assessed in an ongoing prospective longitudinal study at University of California, Davis, Alzheimer's Disease Center from 2000 to 2015. Participants (n = 254) were recruited through a clinic (5%) and community sample (95%). They were clinically confirmed as cognitively normal at baseline and followed up to seven years. Recruitment source, demographic factors (age, gender, race/ethnicity, year of education, APOE ε4 positive), cognitive measures (SENAS test scores), functional assessments (CDR sum of boxes), and neuroimaging measures (total brain volume, total hippocampal volume, white hyperintensity volume) were assessed as predictors of conversion from cognitively normal to mild cognitive impairment using proportional hazards models. ResultsOf 254 participants, 62 (11 clinic, 51 community) progressed to MCI. The clinic-based sample showed an annual conversion rate of 30% (95% CI 17%–54%) per person-year, whereas the community-based sample showed a conversion rate of 5% (95% CI 3%–6%) per person-year. Risk factors for conversion include clinic-based recruitment, being older, lower executive function and worse functional assessment at baseline, and smaller total brain volume. DiscussionOlder adults who sought out a clinical evaluation, even when they are found to have normal cognition, have increased risk of subsequent development of MCI. Results are consistent with other studies showing subjective cognitive complaints are a risk for future cognitive impairment, but extend such findings to show that those who seek evaluation for their complaints are at particularly high risk. Moreover, these individuals have subtle, but significant differences in functional and cognitive abilities that, in the presence of concerns and evidence of atrophy on by brain imaging, warrant continued clinical follow-up. These risk factors could also be used as stratification variables for dementia prevention clinical trial design.

The impact of stratification by implausible energy reporting status on estimates of diet-health relationships.

The food frequency questionnaire (FFQ) is known to be prone to measurement error. Researchers have suggested excluding implausible energy reporters (IERs) of FFQ total energy when examining the relationship between a health outcome and FFQ-reported intake to obtain less biased estimates of the effect of the error-prone measure of exposure; however, the statistical properties of stratifying by IER status have not been studied. Under certain assumptions, including nondifferential error, we show that when stratifying by IER status, the attenuation of the estimated relative risk in the stratified models will be either greater or less in both strata (implausible and plausible reporters) than for the nonstratified model, contrary to the common belief that the attenuation will be less among plausible reporters and greater among IERs. Whether there is more or less attenuation depends on the pairwise correlations between true exposure, observed exposure, and the stratification variable. Thus exclusion of IERs is inadvisable but stratification by IER status can sometimes help. We also address the case of differential error. Examples from the Observing Protein and Energy Nutrition Study and simulations illustrate these results.

Effect of Thermal Stratification on Phytoplankton and Nutrient Dynamics in a Regulated River (Saar, Germany)

AbstractThe weir pool Serrig is the deepest one along the impounded river Saar. Damming caused massive changes in the river's hydrodynamics. We analyzed the spatio‐temporal variability of thermal density stratification in the weir pool and its effect on phytoplankton and nutrient dynamics. In the analysis, continuous measurements from the years 2014 and 2015 were combined with three two‐day sampling campaigns in spring 2015. Thermal stratification occurred regularly in the downstream section of the weir pool during spring and summer and showed a diurnal rhythm. Temperature differences &gt;1 K between the 1 and 2 m water layer were observed during 34 out of 217 days (16%) in 2014, with maximum temperature gradients up to 3.71 K. Whereas the influence of thermal stratification on phytoplankton biomass and distribution was low during the algal bloom in early spring, stratification events between May and July promoted temporary algal blooms in the surface layer with chlorophyll a concentrations up to 98 µg Chla l−1 and a maximum difference between the 1 and 2 m water layer of 36 µg Chla l−1. Some of the stratification events resulted in reduced concentrations of dissolved nutrients in the surface layer as a result of increased uptake by algae, with maximum gradients between the surface and the 8 m water layer of 0.070 mg ortho‐PO43‐‐P l−1, 0.136 mg NH4+−N l−1 and 0.24 mg NO3¯−N l−1. These vertical gradients should be considered in sampling protocols for the assessment of the water quality of temporarily stratified river sections. Copyright © 2016 John Wiley &amp; Sons, Ltd.

Satellite and In Situ Salinity: Understanding Near-Surface Stratification and Subfootprint Variability

Abstract Remote sensing of salinity using satellite-mounted microwave radiometers provides new perspectives for studying ocean dynamics and the global hydrological cycle. Calibration and validation of these measurements is challenging because satellite and in situ methods measure salinity differently. Microwave radiometers measure the salinity in the top few centimeters of the ocean, whereas most in situ observations are reported below a depth of a few meters. Additionally, satellites measure salinity as a spatial average over an area of about 100 × 100 km2. In contrast, in situ sensors provide pointwise measurements at the location of the sensor. Thus, the presence of vertical gradients in, and horizontal variability of, sea surface salinity complicates comparison of satellite and in situ measurements. This paper synthesizes present knowledge of the magnitude and the processes that contribute to the formation and evolution of vertical and horizontal variability in near-surface salinity. Rainfall, freshwater plumes, and evaporation can generate vertical gradients of salinity, and in some cases these gradients can be large enough to affect validation of satellite measurements. Similarly, mesoscale to submesoscale processes can lead to horizontal variability that can also affect comparisons of satellite data to in situ data. Comparisons between satellite and in situ salinity measurements must take into account both vertical stratification and horizontal variability.

Characteristics and Outcomes of Patients With Breast Cancer With Leptomeningeal Metastasis

BackgroundDisease presentation, prognostic factors, and treatment patterns for patients with breast cancer with leptomeningeal metastasis are not well characterized. In this study, we examined patient characteristics and prognostic factors for survival after a diagnosis of leptomeningeal metastasis. Patients and MethodsThree hundred eighteen consecutive patients with breast cancer diagnosed with leptomeningeal metastasis from January 1998 to December 2013 at Memorial Sloan Kettering Cancer Center were identified. Clinicopathologic and treatment information were obtained in a retrospective review. Associations with time from leptomeningeal diagnosis to death were evaluated according to Kaplan–Meier curves, log rank tests, and Cox proportional hazard models. ResultsOf the 318 patients, 44% were hormone receptor-positive (HR+) HER2−, 18% were HR+HER2+, 8.5% were HR−HER2+, 25.5% were triple-negative; and 4% had missing information. The median survival was 3.5 months (95% confidence interval, 3.0-4.0) with 63 patients (20%) surviving >1 year. Recent diagnosis (after 2006), HER2+ subtype, higher performance status, cranial-only involvement, and no evidence of noncentral nervous system disease were independently associated with improved survival in multivariate analysis. ConclusionDespite the improvement noted with the more recent years of diagnosis, survival after a diagnosis of leptomeningeal metastasis remains poor. Similar to patients with parenchymal brain metastasis only, the survival differs among different receptor subtypes. A closer examination to identify factors, such as introduction of new systemic therapies that might contribute to longer-term survival might provide insight to improve management of these patients. In addition, factors we identified that are associated with survival might be considered as stratification variables in the design of future randomized clinical trials in this population.

Application of mobile sampling to investigate spatial variation in fine particle composition

Long-term exposure to particulate matter (PM) is a major contributor to air pollution related deaths. Evidence indicates that metals play an important role in harming human health due to their redox potential. We conducted a mobile sampling campaign in 2013 summer and winter in Pittsburgh, PA to characterize spatial variation in PM2.5 mass and composition. Thirty-six sites were chosen based on three stratification variables: traffic density, proximity to point sources, and elevation. We collected filters in three time sessions (morning, afternoon, and overnight) in each season. X-ray fluorescence (XRF) was used to analyze concentrations of 26 elements: Na, Mg, Al, Si, S, Cl, K, Ca, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Br, Rb, Sr, Zr, Cd, Sb, and Pb. Trace elements had a broad range of concentrations from 0 to 300 ng/m3. Comparison of data from mobile sampling filters with stationary monitors suggested that the mobile sampling strategy did not lead to a biased dataset. We developed Land Use Regression (LUR) models to describe spatial variation of PM2.5, Si, S, Cl, K, Ca, Ti, Cr, Fe, Cu, and Zn. Using ArcGIS-10.3 (ESRI, Redlands, CA), we extracted different independent variables related to traffic influence, land-use type, and facility emissions based on the National Emission Inventory (NEI). To validate LUR models, we used regression diagnostics such as leave-one-out cross validation (LOOCV), mean studentized prediction residual (MSPR), and root mean square of studentized residuals (RMS). The number of predictors in final LUR models ranged from 1 to 6. Models had an average R2 of 0.57 (SD = 0.16). Traffic related variables explained the most variability with an average R2 contribution of 0.20 (SD = 0.20). Overall, these results demonstrated significant intra-urban spatial variability of fine particle composition.

Reanalysis of seasonal and interannual variability of Black Sea fields for 1993–2012

A retrospective analysis has been done for the hydrophysical fields of the Black Sea for 1993–2012 with the assimilation of undisturbed monthly average profiles of temperature and salinity that were obtained by using an original procedure of joint processing of satellite altimetry and rare hydrological observations. The accuracy of the reconstructed fields of temperature and salinity of the Black Sea is evaluated by comparison with the data of sounding from the hydrological stations and the Argo floats. A comparative analysis is performed for the integral characteristics of the fields of temperature, salinity, and kinetic energy with the same characteristics of the reanalysis for 1992–2012 that assimilated the average annual profiles of temperature and salinity, surface temperature and altimetry level of the sea after being adjusted with respect to climate seasonal variability. The proposed procedure of the reanalysis execution allows a more precise reconstruction of the interannual variability of temperature and salinity stratification in the main pycnocline. The correlation between the annual and seasonal variability of the eddy of the wind friction tangential stress and the average kinetic energy at the levels is revealed.

TRAPEZE: a randomised controlled trial of the clinical effectiveness and cost-effectiveness of chemotherapy with zoledronic acid, strontium-89, or both, in men with bony metastatic castration-refractory prostate cancer

Bony metastatic castration-refractory prostate cancer is associated with a poor prognosis and high morbidity. TRAPEZE was a two-by-two factorial randomised controlled trial of zoledronic acid (ZA) and strontium-89 (Sr-89), each combined with docetaxel. All have palliative benefits, are used to control bone symptoms and are used with docetaxel to prolong survival. ZA, approved on the basis of reducing skeletal-related events (SREs), is commonly combined with docetaxel in practice, although evidence of efficacy and cost-effectiveness is lacking. Sr-89, approved for controlling metastatic pain and reducing need for subsequent bone treatments, is generally palliatively used in patients unfit for chemotherapy. Phase II analysis confirmed the safety and feasibility of combining these agents. TRAPEZE aimed to determine the clinical effectiveness and cost-effectiveness of each agent. Patients were randomised to receive six cycles of docetaxel plus prednisolone: alone, with ZA, with a single Sr-89 dose after cycle 6, or with both. Primary outcomes were clinical progression-free survival (CPFS: time to pain progression, SRE or death) and cost-effectiveness. Secondary outcomes were SRE-free interval (SREFI), total SREs, overall survival (OS) and quality of life (QoL). Log-rank test and Cox regression modelling were used to determine clinical effectiveness. Cost-effectiveness was assessed from the NHS perspective and expressed as cost per additional quality-adjusted life-year (QALY). An additional analysis was carried out for ZA to reflect the availability of generic ZA. 757 randomised (median age 68.7 years; Eastern Cooperative Oncology Group scale score 0, 40%; 1, 52%; 2, 8%; prior radiotherapy, 45%); median prostate-specific antigen 143.78 ng/ml (interquartile range 50.8-353.9 ng/ml). Stratified log-rank analysis of CPFS was statistically non-significant for either agent (Sr-89, p = 0.11; ZA, p = 0.45). Cox regression analysis adjusted for stratification variables showed CPFS benefit for Sr-89 [hazard ratio (HR) 0.845, 95% confidence interval (CI) 0.72 to 0.99; p = 0.036] and confirmed no effect of ZA (p = 0.46). ZA showed a significant SREFI effect (HR 0.76; 95% CI 0.63 to 0.93; p = 0.008). Neither agent affected OS (Sr-89, p = 0.74; ZA, p = 0.91), but both increased total cost (vs. no ZA and no Sr-89, respectively); decreased post-trial therapies partly offset costs [net difference: Sr-89 £1341; proprietary ZA (Zometa(®), East Hanover, NJ, USA) £1319; generic ZA £251]. QoL was maintained in all trial arms; Sr-89 (0.08 additional QALYs) and ZA (0.03 additional QALYs) showed slight improvements. The resulting incremental cost-effectiveness ratio (ICER) for Sr-89 was £16,590, with £42,047 per QALY for Zometa and £8005 per QALY for generic ZA. Strontium-89 improved CPFS, but not OS. ZA did not improve CPFS or OS but significantly improved SREFI, mostly post progression, suggesting a role as post-chemotherapy maintenance therapy. QoL was well maintained in all treatment arms, with differing patterns of care resulting from the effects of Sr-89 on time to progression and ZA on SREFI and total SREs. The addition of Sr-89 resulted in additional cost and a small positive increase in QALYs, with an ICER below the £20,000 ceiling per QALY. The additional costs and small positive QALY changes in favour of ZA resulted in ICERs of £42,047 (Zometa) and £8005 for the generic alternative; thus, generic ZA represents a cost-effective option. Additional analyses on the basis of data from the Hospital Episode Statistics data set would allow corroborating the findings of this study. Further research into the use of ZA (and other bone-targeting therapies) with newer prostate cancer therapies would be desirable. Current Controlled Trials ISRCTN12808747. This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 53. See the NIHR Journals Library website for further project information.

Impact of Satellite Remote Sensing Data on Simulations of Coastal Circulation and Hypoxia on the Louisiana Continental Shelf

We estimated surface salinity flux and solar penetration from satellite data, and performed model simulations to examine the impact of including the satellite estimates on temperature, salinity, and dissolved oxygen distributions on the Louisiana continental shelf (LCS) near the annual hypoxic zone. Rainfall data from the Tropical Rainfall Measurement Mission (TRMM) were used for the salinity flux, and the diffuse attenuation coefficient (Kd) from Moderate Resolution Imaging Spectroradiometer (MODIS) were used for solar penetration. Improvements in the model results in comparison with in situ observations occurred when the two types of satellite data were included. Without inclusion of the satellite-derived surface salinity flux, realistic monthly variability in the model salinity fields was observed, but important inter-annual variability was missed. Without inclusion of the satellite-derived light attenuation, model bottom water temperatures were too high nearshore due to excessive penetration of solar irradiance. In general, these salinity and temperature errors led to model stratification that was too weak, and the model failed to capture observed spatial and temporal variability in water-column vertical stratification. Inclusion of the satellite data improved temperature and salinity predictions and the vertical stratification was strengthened, which improved prediction of bottom-water dissolved oxygen. The model-predicted area of bottom-water hypoxia on the Louisiana shelf, an important management metric, was substantially improved in comparison to observed hypoxic area by including the satellite data.

Platelet transfusion versus standard care after acute stroke due to spontaneous cerebral haemorrhage associated with antiplatelet therapy (PATCH): a randomised, open-label, phase 3 trial

Platelet transfusion after acute spontaneous primary intracerebral haemorrhage in people taking antiplatelet therapy might reduce death or dependence by reducing the extent of the haemorrhage. We aimed to investigate whether platelet transfusion with standard care, compared with standard care alone, reduced death or dependence after intracerebral haemorrhage associated with antiplatelet therapy use. We did this multicentre, open-label, masked-endpoint, randomised trial at 60 hospitals in the Netherlands, UK, and France. We enrolled adults within 6 h of supratentorial intracerebral haemorrhage symptom onset if they had used antiplatelet therapy for at least 7 days beforehand and had a Glasgow Coma Scale score of at least 8. With use of a secure web-based system that concealed allocation and used biased coin randomisation, study collaborators randomly assigned participants (1:1; stratified by hospital and type of antiplatelet therapy) to receive either standard care or standard care with platelet transfusion within 90 min of diagnostic brain imaging. Participants and local investigators giving interventions were not masked to treatment allocation, but allocation was concealed from outcome assessors and investigators analysing data. The primary outcome was shift towards death or dependence rated on the modified Rankin Scale (mRS) at 3 months, and analysed by ordinal logistic regression, adjusted for stratification variables and the Intracerebral Haemorrhage Score. The primary analysis was done in the intention-to-treat population and safety analyses were done in the intention-to-treat and as-treated populations. This trial is registered with the Netherlands Trial Register, number NTR1303, and is now closed. Between Feb 4, 2009, and Oct 8, 2015, 41 sites enrolled 190 participants. 97 participants were randomly assigned to platelet transfusion and 93 to standard care. The odds of death or dependence at 3 months were higher in the platelet transfusion group than in the standard care group (adjusted common odds ratio 2·05, 95% CI 1·18-3·56; p=0·0114). 40 (42%) participants who received platelet transfusion had a serious adverse event during their hospital stay, as did 28 (29%) who received standard care. 23 (24%) participants assigned to platelet transfusion and 16 (17%) assigned to standard care died during hospital stay. Platelet transfusion seems inferior to standard care for people taking antiplatelet therapy before intracerebral haemorrhage. Platelet transfusion cannot be recommended for this indication in clinical practice. The Netherlands Organisation for Health Research and Development, Sanquin Blood Supply, Chest Heart and Stroke Scotland, French Ministry of Health.

A Note on the Mantel-Haenszel Estimators When the Common Effect Assumptions Are Violated

Abstract The Mantel-Haenszel estimators for the common effect parameters of stratified 2×2 tables have been widely adopted in epidemiological and clinical studies for controlling the effects of confounding factors. Although the Mantel-Haenszel estimators are simple and effective estimating methods, the correctness of the common effect assumptions cannot be justified in general practices. Also then, the targeted “common effect parameters” do not exist. Under these settings, even if the Mantel-Haenszel estimators have desirable properties, it is quite uncertain what they estimate and how the estimates are interpreted. In this article, we conducted theoretical evaluations for their asymptotic behaviors when the common effect assumptions are violated. We explicitly showed that the Mantel-Haenszel estimators converge to weighted averages of stratum-specific effect parameters and they can be interpreted as intuitive summaries of the stratum-specific effect measures. Also, the Mantel-Haenszel estimators correspond to the standardized effect measures on standard distributions of stratification variables to be the total cohort, approximately. In addition, the ordinary sandwich-type variance estimators are still valid for quantifying variabilities of the Mantel-Haenszel estimators. We implemented numerical studies based on two epidemiologic studies of breast cancer and schizophrenia for evaluating empirical properties of these estimators, and confirmed general validities of these theoretical results.