Use of sacubitril/valsartan in patients with heart failure in primary care in Germany: the AURORA-HF noninterventional study.

BACKGROUND: Sacubitril/valsartan (Sac/Val) is the first angiotensin receptor-neprilysin inhibitor indicated for symptomatic chronic heart failure (HF) with reduced ejection fraction (HFrEF). Given most patients with HF in Germany are managed by general practitioners, AURORA-HF investigated the baseline characteristics and 1­year follow-up of patients starting Sac/Val in primary care in Germany. METHODS: This was a prospective, multicenter, observational study, with all treatment decisions independent of participation. The only inclusion criteria were adults (age ≥ 18 years) with symptomatic HFrEF. The study comprised four groups, depending on therapy on entry: initiation of (1) Sac/Val or (2) other HF therapy; and no change in HF regimen that (3) included or (4) did not include Sac/Val. Baseline data were captured for all groups; 1­year follow-up was recorded in groups 1 and 2. RESULTS: Of 1278 patients in the baseline analyses, 513 (40.1%) had newly started Sac/Val (449 [87.5%] completing the 1­year follow-up), 265 (20.7%) had newly started other HF regimens (245, 92.5%) with 1­year follow-up, while 249 with Sac/Val (19.5%) and 251 without Sac/Val (19.6%) patients had unchanged therapies. Patients treated with Sac/Val had a higher New York Heart Association (NYHA) class at baseline and more often a left ventricular ejection fraction (LVEF) < 35%. The only baseline parameter significantly correlating with Sac/Val discontinuation during the 1­year follow-up was diabetes mellitus (odds ratio: 2.44; 95% confidence interval: 1.14-5.24). In the Sac/Val group, 30.7% of patients were in NYHA class I/II on study entry, improving to 51.0% at 1­year follow-up. In the no Sac/Val group, the corresponding rates of NYHA I and II classes were 49.8% and 58.2%, respectively. The overall adverse event profile of Sac/Val was good, with only 6.0% patients experiencing serious adverse events leading to permanent discontinuation. CONCLUSION: In patients with symptomatic HFrEF treated in primary care, the group in whom Sac/Val was initiated was characterized by a higher NYHA class and lower LVEF compared to patients in whom Sac/Val was not initiated. Sac/Val was well tolerated, with a high proportion completing 1 year of therapy.

The coagulant dipping process of nitrile latex: investigations of former motion effects and coagulant loss into the dipping compound.

Coagulant dipping, the process used in thin glove manufacture, involves electrolyte ions diffusing from the surface of a hand-shaped former into latex compound, causing a deposit (wet gel) to accumulate on the former. In this work, two aspects of the process were examined, both experimentally and theoretically. For the experimental work, a commercial nitrile latex was used. The motion of formers through a latex dipping tank is intuitively expected to affect the electrolyte diffusion and hence the wet gel growth. This was investigated at laboratory scale with small glass formers moving in a metre-long dip tank. Former velocities ranged from zero to almost 0.2 m s-1. No effect of former lateral movement on wet gel thickness was observed. One obvious explanation is that most of the coagulant diffusion occurs within the wet gel deposit, which provides protection to the diffusive flux. However, the critical zone is just ahead of the coagulating front, where coagulant is present in the liquid compound at concentrations below the level needed for coagulation. A fluid mechanical model was constructed that assumed a uniform fluid flow along the side face of a rectangular former. The model confirmed that for calcium nitrate, the most commonly used coagulant, the effect of movement is very small. In the second investigation, coagulant leakage into the host latex compound during the dwell time was investigated by taking samples during repeat static dips. This experiment was modelled using diffusion theory, focusing on the critical zone just outside the wet gel at the point of former withdrawal. The model and experiment agreed well, both showing a small but definite coagulant leakage that tended towards a plateau concentration. Coagulant leakage from a moving former was also considered, from a theoretical perspective. In this case, the mechanism is advective movement of coagulant from the critical zone into the host compound. In the worst case, where all of this coagulant is swept away, the model suggested that the plateau coagulant concentration could reach an amount that would cause coagulation. Reduced flow in the critical zone (boundary layer) and former shape are factors that would reduce leakage.

Variabilities of Magnetic Resonance Imaging-, Computed Tomography-, and Positron Emission Tomography-Computed Tomography-Based Tumor and Lymph Node Delineations for Lung Cancer Radiation Therapy Planning.

PURPOSE: To investigate interobserver delineation variability for gross tumor volumes of primary lung tumors and associated pathologic lymph nodes using magnetic resonance imaging (MRI), and to compare the results with computed tomography (CT) alone- and positron emission tomography (PET)-CT-based delineations. METHODS AND MATERIALS: Seven physicians delineated the tumor volumes of 10 patients for the following scenarios: (1) CT only, (2) PET-CT fusion images registered to CT ("clinical standard"), and (3) postcontrast T1-weighted MRI registered with diffusion-weighted MRI. To compute interobserver variability, the median surface was generated from all observers' contours and used as the reference surface. A physician labeled the interface types (tumor to lung, atelectasis (collapsed lung), hilum, mediastinum, or chest wall) on the median surface. Contoured volumes and bidirectional local distances between individual observers' contours and the reference contour were analyzed. RESULTS: Computed tomography- and MRI-based tumor volumes normalized relative to PET-CT-based volumes were 1.62 ± 0.76 (mean ± standard deviation) and 1.38 ± 0.44, respectively. Volume differences between the imaging modalities were not significant. Between observers, the mean normalized volumes per patient averaged over all patients varied significantly by a factor of 1.6 (MRI) and 2.0 (CT and PET-CT) (P=4.10 × 10-5 to 3.82 × 10-9). The tumor-atelectasis interface had a significantly higher variability than other interfaces for all modalities combined (P=.0006). The interfaces with the smallest uncertainties were tumor-lung (on CT) and tumor-mediastinum (on PET-CT and MRI). CONCLUSIONS: Although MRI-based contouring showed overall larger variability than PET-CT, contouring variability depended on the interface type and was not significantly different between modalities, despite the limited observer experience with MRI. Multimodality imaging and combining different imaging characteristics might be the best approach to define the tumor volume most accurately.

A quality improvement project to improve the Medicare and Medicaid Services (CMS) sepsis bundle compliance rate in a large healthcare system.

Sepsis is a leading cause of mortality and morbidity in hospitalised patients. The Centers for Medicare and Medicaid Services (CMS) mandated that US hospitals report sepsis bundle compliance rate as a quality process measure in October 2015. The specific aim of our study was to improve the CMS sepsis bundle compliance rate from 30% to 40% across 20 acute care hospitals in our healthcare system within 1 year. The study included all adult inpatients with sepsis sampled according to CMS specifications from October 2015 to September 2016. The CMS sepsis bundle compliance rate was tracked monthly using statistical process control charting. A baseline rate of 28.5% with 99% control limits was established. We implemented multiple interventions including computerised decision support systems (CDSSs) to increase compliance with the most commonly missing bundle elements. Compliance reached 42% (99% statistical process control limits 18.4%-38.6%) as CDSS was implemented system-wide, but this improvement was not sustained after CMS changed specifications of the outcome measure. Difficulties encountered elucidate shortcomings of our study methodology and of the CMS sepsis bundle compliance rate as a quality process measure.

Apparent diffusion coefficient (ADC) change on repeated diffusion-weighted magnetic resonance imaging during radiochemotherapy for non-small cell lung cancer: A pilot study.

OBJECTIVES: Serial diffusion-weighted magnetic resonance imaging (DW-MRI) during radiochemotherapy of non-small cell lung cancer (NSCLC) is analyzed to investigate the apparent diffusion coefficient (ADC) as a potential biomarker for tumor response. METHODS: Ten patients underwent DW-MRI prior to and at three and six weeks during radiochemotherapy. Three methods of contouring primary tumors (PT) were performed to evaluate the impact of tumor heterogeneity on ADC values: PTT: whole tumor volume; PTT-N: PTT-necrosis; PTL: small volume of presumed active tumor with low ADC value. Pretreatment and during-treatment absolute ADC values and ADC value changes were analyzed for PT and involved lymph nodes (LN). RESULTS: ADC values for PTT, PTT-N, PTL and LN increased by 8-14% (PT) and 15% (LN) at three weeks, and 19-26% and 23% at 6 weeks post initial treatment (p=0.04-0.002). Average percent ADC value increase was smaller than tumor volume regression (p=0.06-0.0005). Patients with overall survival <12 months had a lower increase of ADC values compared to longer surviving patients (p=0.008 for PTT). CONCLUSIONS: Significant ADC value increases during radiochemotherapy for non-small cell lung cancer were observed. ADC value change during treatment appears to be an independent marker of patient outcome and warrants further investigation.

ICU Telemedicine Comanagement Methods and Length of Stay.

BACKGROUND: Studies have identified processes that are associated with more favorable length of stay (LOS) outcomes when an ICU telemedicine program is implemented. Despite these studies, the relation of the acceptance of ICU telemedicine management services by individual ICUs to LOS outcomes is unknown. METHODS: This is a single ICU telemedicine center study that compares LOS outcomes among three groups of intensivist-staffed mixed medical-surgical ICUs that used alternative comanagement strategies. The proportion of provider orders recorded by an ICU telemedicine provider to all recorded orders was compared among ICUs that used a monitor and notify comanagement approach, a direct intervention with timely notification process, and ICUs that used a mix of these two approaches. The primary outcome was acuity-adjusted hospital LOS. RESULTS: ICUs that used the direct intervention with timely notification strategy had a significantly larger proportion of provider orders recorded by ICU telemedicine physicians than the mixed methods of comanagement group, which had a larger proportion than ICUs that used the monitor and notify method (P < .001). Acuity-adjusted hospital LOS was significantly lower for the direct intervention with timely notification comanagement strategy (0.68; 0.65-0.70) compared with the mixed methods group (0.70 [0.69-0.72]; P = .01), which was significantly lower than the monitor and notify group (0.83 [0.80-0.86]; P < .001). CONCLUSIONS: Direct intervention with timely notification strategies of ICU telemedicine comanagement were associated with shorter LOS outcomes than monitor and notify comanagement strategies.

Real-Time Automated Sampling of Electronic Medical Records Predicts Hospital Mortality.

BACKGROUND: Real-time automated continuous sampling of electronic medical record data may expeditiously identify patients at risk for death and enable prompt life-saving interventions. We hypothesized that a real-time electronic medical record-based alert could identify hospitalized patients at risk for mortality. METHODS: An automated alert was developed and implemented to continuously sample electronic medical record data and trigger when at least 2 of 4 systemic inflammatory response syndrome criteria plus at least one of 14 acute organ dysfunction parameters was detected. The systemic inflammatory response syndrome and organ dysfunction alert was applied in real time to 312,214 patients in 24 hospitals and analyzed in 2 phases: training and validation datasets. RESULTS: In the training phase, 29,317 (18.8%) triggered the alert and 5.2% of such patients died, whereas only 0.2% without the alert died (unadjusted odds ratio 30.1; 95% confidence interval, 26.1-34.5; P < .0001). In the validation phase, the sensitivity, specificity, area under the curve, and positive and negative likelihood ratios for predicting mortality were 0.86, 0.82, 0.84, 4.9, and 0.16, respectively. Multivariate Cox-proportional hazard regression model revealed greater hospital mortality when the alert was triggered (adjusted hazards ratio 4.0; 95% confidence interval, 3.3-4.9; P < .0001). Triggering the alert was associated with additional hospitalization days (+3.0 days) and ventilator days (+1.6 days; P < .0001). CONCLUSION: An automated alert system that continuously samples electronic medical record data can be implemented, has excellent test characteristics, and can assist in the real-time identification of hospitalized patients at risk for death.

Estimation of optimal b-value sets for obtaining apparent diffusion coefficient free from perfusion in non-small cell lung cancer.

The purpose of this study was to determine optimal sets of b-values in diffusion-weighted MRI (DW-MRI) for obtaining monoexponential apparent diffusion coefficient (ADC) close to perfusion-insensitive intravoxel incoherent motion (IVIM) model ADC (ADCIVIM) in non-small cell lung cancer. Ten subjects had 40 DW-MRI scans before and during radiotherapy in a 1.5 T MRI scanner. Respiratory triggering was applied to the echo-planar DW-MRI with TR ≈ 4500 ms, TE = 74 ms, eight b-values of 0-1000 µs µm(-2), pixel size = 1.98 × 1.98 mm(2), slice thickness = 6 mm, interslice gap = 1.2 mm, 7 axial slices and total acquisition time ≈6 min. One or more DW-MRI scans together covered the whole tumour volume. Monoexponential model ADC values using various b-value sets were compared to reference-standard ADCIVIM values using all eight b-values. Intra-scan coefficient of variation (CV) of active tumour volumes was computed to compare the relative noise in ADC maps. ADC values for one pre-treatment DW-MRI scan of each of the 10 subjects were computed using b-value pairs from DW-MRI images synthesized for b-values of 0-2000 µs µm(-2) from the estimated IVIM parametric maps and corrupted by various Rician noise levels. The square root of mean of squared error percentage (RMSE) of the ADC value relative to the corresponding ADCIVIM for the tumour volume of the scan was computed. Monoexponential ADC values for the b-value sets of 250 and 1000; 250, 500 and 1000; 250, 650 and 1000; 250, 800 and 1000; and 250-1000 µs µm(-2) were not significantly different from ADCIVIM values (p > 0.05, paired t-test). Mean error in ADC values for these sets relative to ADCIVIM were within 3.5%. Intra-scan CVs for these sets were comparable to that for ADCIVIM. The monoexponential ADC values for other sets-0-1000; 50-1000; 100-1000; 500-1000; and 250 and 800 µs µm(-2) were significantly different from the ADCIVIM values. From Rician noise simulation using b-value pairs, there was a wide range of acceptable b-value pairs giving small RMSE of ADC values relative to ADCIVIM. The pairs for small RMSE had lower b-values as the noise level increased. ADC values of a two b-value set-250 and 1000 µs µm(-2), and all three b-value sets with 250, 1000 µs µm(-2) and an intermediate value approached ADCIVIM, with relative noise comparable to that of ADCIVIM. These sets may be used in lung tumours using comparatively short scan and post-processing times. Rician noise simulation suggested that the b-values in the vicinity of these experimental best b-values can be used with error within an acceptable limit. It also suggested that the optimal sets will have lower b-values as the noise level becomes higher.

Lung cancer screening with low-dose computed tomography: an analysis of the MEDCAC decision.

Lung cancer is the leading cause of cancer death in the United States and worldwide. However, among the top 4 deadliest cancers, lung cancer is the only one not subject to routine screening. Optimism for an effective lung cancer-screening examination soared after the release of the National Lung Screening Trial results in November 2011. Since then, nearly 40 major medical societies and organizations have endorsed low-dose computed tomography (LDCT) screening. In December 2013, the United States Preventive Services Task Force also endorsed LDCT. However, the momentum for LDCT screening slowed in April 2014 when the Medicare Evidence Development and Coverage Advisory Committee (MEDCAC) panel concluded that there was not enough evidence to justify the annual use of LDCT scans for the detection of early lung cancer. This article briefly reviews the epidemiology of lung cancer, the National Lung Screening Trial study results, and the growing national endorsement of LDCT from a variety of key stakeholder organizations. We subsequently analyze and offer our evidence-based counterpoints to the major assumptions underlying the MEDCAC decision.

MR imaging evaluation of pericardial constriction.

Abnormal thickening or rigidity of the pericardium may compromise normal cardiac function. This condition is known as pericardial constriction, or constrictive pericarditis. Several imaging modalities are used to evaluate the pericardium, including MR, computed tomography, and echocardiography, which can all play a complementary role aiding diagnosis. This article focuses on MR imaging and its role in the detection and evaluation of pericardial constriction. MR imaging has many advantages compared with other modalities including precise delineation of the pericardial thickness, evaluation of ventricular function, detection of wall motion abnormalities, and provision of information about common (and potentially harmful) sequelae of pericardial constriction.

Critical care telemedicine: evolution and state of the art.

OBJECTIVES: To review the growth and current penetration of ICU telemedicine programs, association with outcomes, studies of their impact on medical education, associations with medicolegal risks, identify program revenue sources and costs, regulatory aspects, and the ICU telemedicine research agenda. DATA SOURCES: Review of the published medical literature, governmental documents, and opinions of experts from the Society of Critical Care Medicine ICU Telemedicine Committee. DATA SYNTHESIS: Formal ICU telemedicine programs now support 11% of nonfederal hospital critically ill adult patients. There is increasingly robust evidence of association with lower ICU (0.79; 95% CI, 0.65-0.96) and hospital mortality (0.83; 95% CI, 0.73-0.94) and shorter ICU (-0.62 d; 95% CI, -1.21 to -0.04 d) and hospital (-1.26 d; 95% CI, -2.49 to -0.03 d) length of stay. Physicians in training report experiences with telemedicine intensivists that are positive and increased patient safety. Early studies suggest that implementation of ICU telemedicine programs has been associated with lower numbers of malpractice claims and costs. The requirements for Medicare reimbursement and states with legislation addressing providing professional services by telemedicine are detailed. CONCLUSIONS: The inclusion of an ICU telemedicine program as a major part of their critical care delivery paradigm has been implemented for 11% of critically ill U.S. adults as a solution for the problem of access to adult critical care services. Implementation of an ICU telemedicine program is one practical way to increase access and reduce mortality as well as length of stay. ICU telemedicine research including comparative effectiveness studies is urgently needed.

Responsive Design, Weighting, andVariance Estimation in the 2006-2010 National Survey of Family Growth.

Objective-The National Survey of Family Growth (NSFG) collects data on pregnancy, childbearing, men's and women's health, and parenting from a national sample of men and women aged 15-44 in the United States. The 2006-2010 NSFG design was a significant departure from the previous periodic design, used in 1973-2002. This report shows fieldwork results and weighting, imputation, and variance estimation procedures. The report should be useful to users of the 2006-2010 public-use data file and to survey methodologists wishing to learn how the NSFG was conducted. Methods-NSFG's new design is based on an independent national probability sample of men and women aged 15-44. The University of Michigan's Institute for Social Research conducted fieldwork under a contract with the National Center for Health Statistics. Professional female interviewers conducted in-person, face-to-face interviews using laptop computers. A responsive design approach was used in planning and managing the fieldwork for NSFG to control costs and reduce nonresponse bias. Results-The 2006-2010 NSFG is based on 22,682 completed interviews-10,403 interviews with men and 12,279 with women. Interviews with men lasted an average of 52 minutes, and for women, 71 minutes. Weighted response rates were 75% among men, 78% among women, and 77% overall. Analysis of NSFG data requires the use of sampling weights and estimation of sampling errors that account for the complex sample design and estimation features of the survey. Sampling weights are provided on the data files. The rate of missing data in the survey is generally low.

Responsive survey design, demographic data collection, and models of demographic behavior.

To address declining response rates and rising data-collection costs, survey methodologists have devised new techniques for using process data ("paradata") to address nonresponse by altering the survey design dynamically during data collection. We investigate the substantive consequences of responsive survey design-tools that use paradata to improve the representative qualities of surveys and control costs. By improving representation of reluctant respondents, responsive design can change our understanding of the topic being studied. Using the National Survey of Family Growth Cycle 6, we illustrate how responsive survey design can shape both demographic estimates and models of demographic behaviors based on survey data. By juxtaposing measures from regular and responsive data collection phases, we document how special efforts to interview reluctant respondents may affect demographic estimates. Results demonstrate the potential of responsive survey design to change the quality of demographic research based on survey data.

The 2006-2010 National Survey of Family Growth: sample design and analysis of a continuous survey.

OBJECTIVE: The National Survey of Family Growth (NSFG) collects data on pregnancy, childbearing, men's and women's health, and parenting from a national sample of women and men 15-44 years of age in the United States. This report describes the sample design for the NSFG's new continuous design and the effects of that design on weighting and variance estimation procedures. A working knowledge of this information is important for researchers who wish to use the data. Two data files are being released--the first covering 2.5 years (30 months) of data collection and the second after all data have been collected. This report is being released with the first data file. A later report in this Series will include specific results of the weighting, imputation, and variance estimation. METHODS: The NSFG's new design is based on an independent, national probability sample of women and men 15-44 years of age. Fieldwork was carried out by the University of Michigan's Institute for Social Research (ISR) under a contract with the National Center for Health Statistics (NCHS). In-person, face-to-face interviews were conducted by professional female interviewers using laptop computers. RESULTS: Analysis of NSFG data requires the use of sampling weights and estimation of sampling errors that account for the complex sample design and estimation features of the survey. Sampling weights are provided on the data files. The rate of missing data in the survey is generally low. However, missing data were imputed for about 600 key variables (called "recodes") that are used for most analyses of the survey. Imputation was accomplished using a multiple regression procedure with software called IVEware, available from the University of Michigan website.

Experimental Studies of Disclosure Risk, Disclosure Harm, Topic Sensitivity, and Survey Participation.

This article extends earlier work (Couper et al. 2008) that explores how survey topic and risk of identity and attribute disclosure, along with mention of possible harms resulting from such disclosure, affect survey participation. The first study uses web-based vignettes to examine respondents' expressed willingness to participate in the hypothetical surveys described, whereas the second study uses a mail survey to examine actual participation. Results are consistent with the earlier experiments. In general, we find that under normal survey conditions, specific information about the risk of identity or attribute disclosure influences neither respondents' expressed willingness to participate in a hypothetical survey nor their actual participation in a real survey. However, when the possible harm resulting from disclosure is made explicit, the effect on response becomes significant. In addition, sensitivity of the survey topic is a consistent and strong predictor of both expressed willingness to participate and actual participation.

Particulate ionomer films prepared from dispersions of crosslinked polymer colloids: a structure-property study.

Polymers with properties that are governed by ionic interactions in discrete regions are termed ionomers. This work presents a comprehensive study of polymer films prepared from dispersions of crosslinked poly(butadiene/methacrylic acid) (poly(Bd/MAA)) particles in water. We showed recently [O. Pinprayoon, R. Groves, B.R. Saunders, J. Colloid Interface Sci. 321 (2008) 315-322] that poly(Bd/MAA) particles could be considered to have a core-shell structure with a MAA-rich shell. The poly(Bd/MAA) dispersions used here contained added ZnO particles which provided a source of Zn(2+). The films were investigated using AFM, FTIR, small-angle X-ray scattering (SAXS), dynamic mechanical thermal analysis (DMTA) and tensile stress vs. strain measurements. The films showed differences and similarities to conventional ionomers which are discussed. The FTIR data revealed that the Zn(2+) ions formed ionic crosslinks with the carboxylate groups (RCOO(-)). Mechanical property studies were conducted using DMTA and stress vs. strain measurements. The DMTA data revealed evidence of two main phases in the systems: a poly(Bd)-rich phase and a poly(MAA)-rich phase. A third phase was also found; which was ascribed to an interphase between the particle core and shell. The SAXS data showed that the films were composed of distinct poly(Bd/MAA) particles, implying that only partial coalescence occurred across the particle interfaces during formation of these particulate ionomer films. Ionic crosslinking of the particles was suggested to occur in the interfacial region (knit regions). The SAXS data also showed scattering from Zn(2+)(RCOO(-)) ionic-aggregates. These ionic aggregates had an average separation of 2.9 nm, which is much smaller than that for conventional ionomers. Interestingly, the concentration of these aggregates passed through a maximum and decreased as the degree of neutralisation of the MAA groups approached 100%. A conceptual model for the structure of these unconventional ionomers is discussed.

Planning and development of the continuous National Survey of Family Growth.

OBJECTIVES: This report describes how the continuous National Survey of Family Growth (NSFG) (begun in 2006) was designed, planned, and implemented. The NSFG is a continuous national survey of men and women 15-44 years of age designed to provide national estimates of factors affecting pregnancy and birth rates; men's and women's health; and parenting. METHODS: The survey used in-person, face-to-face interviews conducted by trained female interviewers. One person per household was interviewed from a national area probability sample. The data collection used computer-assisted personal interviewing (CAPI). Separate questionnaires were used for male and female respondents. The last section of the questionnaires used a self-administered technique called audio computer-assisted self-interviewing or ACASI. Each data collection period lasted 12 weeks-10 weeks for "Phase 1," the main data collection protocol, and 2 weeks for "Phase 2," an intensive attempt to locate and interview nonrespondents. RESULTS: Each year, about 5,000 persons were interviewed in about 33 areas, called primary sampling units (PSUs). Over a 4-year period, 110 PSUs will be used. This report gives an overview of the procedures used in the conduct of the continuous NSFG. A later report will describe response rates and other results of the data collection, but the early fieldwork has gone well.