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Excessive synaptic loss is thought to be one of the earliest events in Alzheimer's disease. Amyloid beta (Aβ), a peptide secreted in an activity-modulated manner by neurons, has been implicated in the pathogenesis of Alzheimer's disease by removing dendritic spines, sites of excitatory synaptic transmission. However, issues regarding the subcellular source of Aβ, as well as the mechanisms of its production and actions that lead to synaptic loss, remain poorly understood. In rat organotypic slices, we found that acute overproduction of either axonal or dendritic Aβ reduced spine density and plasticity at nearby (∼5–10 μm) dendrites. The production of Aβ and its effects on spines were sensitive to blockade of action potentials or nicotinic receptors; the effects of Aβ (but not its production) were sensitive to NMDA receptor blockade. Notably, only 30–60 min blockade of Aβ overproduction permitted induction of plasticity. Our results indicate that continuous overproduction of Aβ at dendrites or axons acts locally to reduce the number and plasticity of synapses. [ABSTRACT FROM AUTHOR]

Background: The outcomes after elective surgery in patients with cirrhosis have not been well studied. Study Design: We used the Nationwide Inpatient Sample (NIS) to identify all patients undergoing elective surgery for four index operations (cholecystectomy, colectomy, abdominal aortic aneurysm repair, and coronary artery bypass grafting) from 1998 to 2005. Elixhauser comorbidity measures were used to characterize patients'' disease burden. Three distinct groups were created based on severity of liver disease: patients without cirrhosis (NON-CIRR), those with cirrhosis (CIRR), and patients with cirrhosis complicated by portal hypertension (PHTN). In-hospital mortality was the primary endpoint. Results: There were 22,569 patients with cirrhosis (of whom 4,214 had PHTN) who underwent 1 of the 4 index operations compared with approximately 2.8 million patients without cirrhosis having these operations. Patients with CIRR or PHTN were more likely to be women (49.5% versus 44.0%, p < 0.0001) and were less likely to be treated in a large hospital (62.8% versus 67.6%, p < 0.0001) than NON-CIRR patients. Length of hospital stay and total charges per hospitalization increased with severity of liver disease for all operations (p < 0.001, respectively). Adjusted mortality rates increased with increasing liver disease for each operation (cholecystectomy: CIRR hazard ratio [HR] 3.4, 95% CI 2.3 to 5.0; PHTN HR 12.3, 95% CI 7.6 to 19.9; colectomy: CIRR HR 3.7, 95% CI 2.6 to 5.2; PHTN HR 14.3, 95% CI 9.7 to 21.0; coronary artery bypass grafting: CIRR HR 8.0, 95% CI 5.0 to 13.0, PHTN HR 22.7, 95% CI 10.0 to 53.8; abdominal aortic aneurysm: CIRR HR 5.0, 95% CI 2.6 to 9.8, PHTN HR 7.8, 95% CI 2.3 to 26.5). Conclusions: In-hospital mortality, length of stay, and total hospital charges are significantly higher after elective surgery in cirrhotic patients, even in the absence of portal hypertension. Careful decision-making about surgery in these patients is critical as the nationwide increase in hepatitis C and cirrhosis continues. [Copyright &y& Elsevier]

Diagnosis of hand ischemia secondary to an arteriovenous (AV) hemodialysis access is predominantly based on clinical findings. Occasionally, this diagnosis is unclear and more objective diagnostic testing is needed. No validated method of objective testing currently exists. The purpose of this study is to evaluate digital pressure measurements in the diagnosis of AV access-induced hand ischemia. A case-control study of 40 patients with an upper extremity AV access consisted of 15 patients (38%) with clinical AV access-induced hand ischemia and 25 patients (62%) without clinical evidence of ischemia. Arterial pressure in the third finger ipsilateral to the AV access was measured by digital photoplethysmography. Basal digital pressure (BDP), digital to contralateral brachial index (DBI), and change in digital pressure with access compression (CDP) were determined. Logistic regression modeling with gains tables and ROC calculations were used to determine optimal test thresholds and to test model discrimination for predicting AV access-induced hand ischemia. The mean BDP (30 vs 102mmHg; p < 0.001) and mean DBI (0.3 vs 0.8; p < 0.001) were significantly lower in patients with AV access-induced hand ischemia than in those without. The accuracy for determining hand ischemia using a thresholdadjusted BDP of 60 mmHg was 92% (sensitivity 100%, specificity 87%) and using DBI of 0.4 was 94% (sensitivity 92%, specificity 96%). While the mean CDP was significantly higher in patients with hand ischemia (85 vs 40; p < 0.001), the accuracy for predicting ischemia was marginal (78%). In conclusion, a BDP less than 60mmHg or a DBI less than 0.4 in a patient with an AV access were highly associated with hand ischemia. CDP's marginal discrimination ability likely stems from the presence of asymptomatic physiologic steal in the group without clinical steal. Nonetheless, CDP may be useful in identifying patients with ischemia who will not benefit from an intervention that specifically targets the AV access. [ABSTRACT FROM AUTHOR]

Drosophila N-cadherin is required for the formation of precise patterns of connections in the fly brain. Alternative splicing is predicted to give rise to 12 N-cadherin isoforms. We identified an N-cadherin allele, N-cad18Astop, that eliminates the six isoforms containing alternative exon ISA and demonstrate that it strongly disrupts the connections of Ri photoreceptor neurons. During the first half of pupal development, N-cadherin is required for R7 growth cones to terminate within a temporary target layer in the medulla. N-cadherin isoforms containing exon 18B are sufficient for this initial targeting. By contrast, IBA isoforms are preferentially expressed in R7 during the second half of pupal development and are necessary for R7 to terminate in the appropriate synaptic layer in the medulla neuropil. Transgene rescue experiments suggest that differences in isoform expression, rather than biochemical differences between isoforms, underlie the 18A isoform requirement in R7 neurons. [ABSTRACT FROM AUTHOR]

EphA4 is a member of the Eph family of receptor tyrosine kinases and has important functions in the developing and adult nervous system. In the adult, EphA4 is enriched in the hippocampus and cortex, two brain structures critical for learning and memory. To identify reagents that can discriminate between the many Eph receptors and selectively target EphA4, we used a phage display approach. We identified three 12-amino acid peptides that preferentially bind to EphA4. Despite lack of a common sequence motif, these peptides compete with each other for binding to EphA4 and antagonize ephrin binding and EphA4 activation at micromolar concentrations, indicating that they bind with high affinity to the ephrin-binding site. Furthermore, one of the peptides perturbs the segmental migration of EphA4-positive neural crest cells in chick trunk organotypic explants. Hence, this peptide can disrupt the physiological function of endogenous EphA4 in situ. We also identified additional peptides that bind to EphA5 and EphA7, two other receptors expressed in the nervous system. This panel of peptides may lead to the development of pharmaceuticals that differentially target Eph receptors to modulate neuronal function in specific regions of the nervous system. [Copyright &y& Elsevier]

Communication between glial cells and neurons is emerging as a critical parameter of synaptic function. However, the molecular mechanisms underlying the ability of glial cells to modify synaptic structure and physiology are poorly understood. Here we describe a repulsive interaction that regulates postsynaptic morphology through the EphA4 receptor tyrosine kinase and its ligand ephrin-A3. EphA4 is enriched on dendritic spines of pyramidal neurons in the adult mouse hippocampus, and ephrin-A3 is localized on astrocytic processes that envelop spines. Activation of EphA4 by ephrin-A3 was found to induce spine retraction, whereas inhibiting ephrin/EphA4 interactions distorted spine shape and organization in hippocampal slices. Furthermore, spine irregularities in pyramidal neurons from EphA4 knockout mice and in slices transfected with kinase-inactive EphA4 indicated that ephrin/EphA4 signaling is critical for spine morphology. Thus, our data support a model in which transient interactions between the ephrin-A3 ligand and the EphA4 receptor regulate the structure of excitatory synaptic connections through neuroglial cross-talk. [ABSTRACT FROM AUTHOR]

To establish a more reliable reference instrument for calibration normalization, this paper examines the differences between the various thermal infrared imager channels on a set of research and operational satellites. Mean brightness temperatures from the Visible Infrared Scanner (VIRS) on the Tropical Rainfall Measuring Mission (TRMM) satellite and the second Along-Track Scanning Radiometer (ATSR-2) on the second European Remote Sensing Satellite (ERS-2) are correlated with matched data from the eighth Geostationary Operational Environmental Satellite (GOES-8), the fifth Geostationary Meteorological Satellite (GMS-5), and with each other. VIRS data are also correlated with the Terra satellite's Moderate Resolution Imaging Spectroradiometer (MODIS) provisional data as a preliminary assessment of their relative calibrations. As an additional check on their long-term stability, the VIRS data are compared to the broadband longwave radiances of the Clouds and the Earth's Radiant Energy System (CERES) scanners on TRMM. No statistically significant trend in the calibration of any of the three (3.7, 10.8, and 12.0 µm) VIRS thermal channels could be detected from the comparisons with CERES data taken during 1998 and 2000 indicating that the VIRS channels can serve as a reliable reference for intercalibrating satellite imagers. However, a small day-night difference in the VIRS thermal channels detected at very low temperatures should be taken into account. In general, most of the channels agreed to within less than ±0.7 K over a temperature range between 200 and 300 K. Some of the smaller differences can be explained by spectral differences in the channel response functions. A few larger differences were found at 200 K for some of the channels suggesting some basic calibration differences for lower temperatures. A nearly 3-K bias in the ATSR-2 11-µm channel relative to VIRS and GOES-8 was found at the cold end of the temperature range. The... [ABSTRACT FROM AUTHOR]

Operational meteorological satellites generally lack reliable onboard calibration systems for solar-imaging channels. Current methods for calibrating these channels and for normalizing similar channels on contemporaneous satellite imagers typically rely on a poorly calibrated reference source. To establish a more reliable reference instrument for calibration normalization, this paper examines the use of research satellite imagers that maintain their solar-channel calibrations by using onboard diffuser systems that rely on the sun as an absolute reference. The Visible Infrared Scanner (VIRS) on the Tropical Rainfall Measuring Mission (TRMM) satellite and the second Along-Track Scanning Radiometer (ATSR-2) on the second European Remote Sensing Satellite (ERS-2) are correlated with matched data from the eighth Geostationary Operational Environmental Satellite (GOES-8), the fifth Geostationary Meteorological satellite (GMS-5), and with each other to examine trends in the solar channels. VIRS data are also correlated with the Terra satellite's Moderate Resolution Imaging Spectroradiometer (MODIS) provisional data as a preliminary assessment of their relative calibrations. As an additional check on their long-term stability, the VIRS data are compared to the relevant corresponding broadband shortwave radiances of the Clouds and the Earth's Radiant Energy System (CERES) scanners on TRMM. No statistically significant trend in the calibration of the VIRS 0.65- and 1.64-µm channels could be detected from the comparisons with CERES data taken during 1998 and 2000. The VIRS-to-GOES-8 correlations revealed an annual degradation rate for the GOES-8 visible (0.67 µm) channel of ∼7.5% and an initial drop of 16% in the gain from the prelaunch value. The slopes in the GOES-8 visible-channel gain trend lines derived from VIRS data taken after January 1998 and ATSR-2 data taken between October 1995 and December 1999 differed by only 1%-2% indicating that both... [ABSTRACT FROM AUTHOR]

Background: Confounding by indication is a serious threat to comparative studies using real world data. We assessed the utility of automated data-adaptive analytic approach for confounding adjustment when both claims and clinical registry data are available. Methods: We used a comparative study example of carotid artery stenting (CAS) vs. carotid endarterectomy (CEA) in 2005–2008 when CAS was only indicated for patients with high surgical risk. We included Medicare beneficiaries linked to the Society for Vascular Surgery's Vascular Registry >65 years old undergoing CAS/CEA. We compared hazard ratios (HRs) for death while adjusting for confounding by combining various 1) Propensity score (PS) modeling strategies (investigator-specified [IS-PS] vs. automated data-adaptive [ada-PS]); 2) data sources (claims-only, registry-only and claims-plus-registry); and 3) PS adjustment approaches (matching vs. quintiles-adjustment with/without trimming). An HR of 1.0 was used as a benchmark effect estimate based on CREST trial. Results: The cohort included 1,999 CAS and 3,255 CEA patients (mean age 76). CAS patients were more likely symptomatic and at high surgical risk, and experienced higher mortality (crude HR = 1.82 for CAS vs. CEA). HRs from PS-quintile adjustment without trimming were 1.48 and 1.52 for claims-only IS-PS and ada-PS, 1.51 and 1.42 for registry-only IS-PS and ada-PS, and 1.34 and 1.23 for claims-plus-registry IS-PS and ada-PS, respectively. Estimates from other PS adjustment approaches showed similar patterns. Conclusions: In a comparative effectiveness study of CAS vs. CEA with strong confounding by indication, ada-PS performed better than IS-PS in general, but both claims and registry data were needed to adequately control for bias. [ABSTRACT FROM AUTHOR]

Background: Surgical patients with limited digital literacy may experience reduced telemedicine access. We investigated racial/ethnic and socioeconomic disparities in telemedicine compared with in-person surgical consultation during the coronavirus disease 2019 (COVID-19) pandemic.Study Design: Retrospective analysis of new visits within the Division of General & Gastrointestinal Surgery at an academic medical center occurring between March 24 through June 23, 2020 (Phase I, Massachusetts Public Health Emergency) and June 24 through December 31, 2020 (Phase II, relaxation of restrictions on healthcare operations) was performed. Visit modality (telemedicine/phone vs in-person) and demographic data were extracted. Bivariate analysis and multivariable logistic regression were performed to evaluate associations between patient characteristics and visit modality.Results: During Phase I, 347 in-person and 638 virtual visits were completed. Multivariable modeling demonstrated no significant differences in virtual compared with in-person visit use across racial/ethnic or insurance groups. Among patients using virtual visits, Latinx patients were less likely to have video compared with audio-only visits than White patients (OR, 0.46; 95% CI 0.22-0.96). Black race and insurance type were not significant predictors of video use. During Phase II, 2,922 in-person and 1,001 virtual visits were completed. Multivariable modeling demonstrated that Black patients (OR, 1.52; 95% CI 1.12-2.06) were more likely to have virtual visits than White patients. No significant differences were observed across insurance types. Among patients using virtual visits, race/ethnicity and insurance type were not significant predictors of video use.Conclusion: Black patients used telemedicine platforms more often than White patients during the second phase of the COVID-19 pandemic. Virtual consultation may help increase access to surgical care among traditionally under-resourced populations. [ABSTRACT FROM AUTHOR]

Background: Racial disparities in colorectal cancer (CRC) screening are frequently attributed to variations in insurance status. The objective of this study was to ascertain whether universal insurance would lead to more equitable utilization of CRC screening for black patients in comparison with white patients.Methods: Claims data from TRICARE (insurance coverage for active, reserve, and retired members of the US Armed Services and their dependents) for 2007-2010 were queried for adults aged 50 years in 2007, and they were followed forward in time for 4 years (ages, 50-53 years) to identify their first lower endoscopy and/or fecal occult blood test (FOBT). Variations in CRC screening were compared with descriptive statistics and multivariate logistic regression.Results: Among the 24,944 patients studied, 69.2% were white, 20.3% were black, 4.9% were Asian, and 5.6% were other. Overall, 54.0% received any screening: 83.7% received endoscopy, and 16.3% received FOBT alone. Compared with whites, black patients had higher screening rates (56.5%) and had 20% higher risk-adjusted odds of being screened (95% confidence interval [CI], 1.11-1.29). Asian patients had a likelihood of screening similar to that of white patients (odds ratio [OR], 1.06; 95% CI, 0.92-1.23). Females (OR, 1.20; 95% CI, 1.10-1.33), active-duty personnel (OR, 1.15; 95% CI, 1.06-1.25), and officers (OR, 1.28; 95% CI, 1.18-1.37) were also more likely to be screened.Conclusion: Within an equal-access, universal health care system, black patients had higher rates of CRC screening in comparison with prior reports and even in comparison with white patients within the population. These findings highlight the need to understand and develop meaningful approaches for promoting more equitable access to preventative care. Moreover, equal-access, universal health insurance for both the military and civilian populations can be presumed to improve access for underserved minorities. [ABSTRACT FROM AUTHOR]

Arising from: J. Laurén et al. 457, 1128–1132 (2009); Laurén et al. replyIncreased levels of brain amyloid-?, a secreted peptide cleavage product of amyloid precursor protein (APP), is believed to be critical in the aetiology of Alzheimer’s disease. Increased amyloid-? can cause synaptic depression, reduce the number of spine protrusions (that is, sites of synaptic contacts) and block long-term synaptic potentiation (LTP), a form of synaptic plasticity; however, the receptor through which amyloid-? produces these synaptic perturbations has remained elusive. Laurén et al. suggested that binding between oligomeric amyloid-? (a form of amyloid-? thought to be most active) and the cellular prion protein (PrPC) is necessary for synaptic perturbations. Here we show that PrPC is not required for amyloid-?-induced synaptic depression, reduction in spine density, or blockade of LTP; our results indicate that amyloid-?-mediated synaptic defects do not require PrPc. [ABSTRACT FROM AUTHOR]

The author reflects on health-related quality of life (HRQoL) in the U.S. He states that assessing changes in HRQoL allows health personnel to measure a more comprehensive outcome that reflects a patient. He cites that HRQoL has been used as predicator of outcomes, specially survival, in patients with coronary heart disease. He cites that health personnel must incorporate measure of HRQoL to their clinical research designs to analyze composite outcomes relevant to the patient's perspective

Background: Shared decision making and patient‐centred communication have become part of pre‐procedural decisions and perioperative care across medical specialties. However, gaps exist in patient communication about the implanted device received and the benefits in sharing information about their procedure and device. Objective: To understand the patients' knowledge of identifying information for their implanted devices and perspectives on sharing their implanted device information. Methods: Four focus groups were conducted with patients who had received a cardiac or vascular implanted device from one of the study sites within the previous 6 months. Data were transcribed and thematically analysed. Results: Five themes emerged: lack of awareness of identifying information on implanted devices; value of information on implanted devices; varying trust with sharing device information; perceived risk with sharing device information; and lack of consensus on a systematic process for tracking implanted devices. Discussion: Patients desire post‐procedural information on their implanted device and a designated plan for longitudinal follow‐up, but lack trust and perceive risk with broadly sharing their implanted device information. Conclusion: After receiving an implanted device, post‐procedural patient communication needs to be expanded to include identifying information on the device including the unique device identifier, how long‐term tracking will be supported and the process for notification in case of a problem with the device. This communication should also include education on how sharing device information supports patients' long‐term health care, post‐market safety surveillance and research. Patient or Public Contribution: The research team included members who were also patients with implanted devices. [ABSTRACT FROM AUTHOR]

Background: Conventional economic principles suggest that increases in competition are associated with price decreases. The purpose of this study is to determine whether this association holds true between objective measures of hospital competition and gross charges, by analyzing standardized operations where variations in costs should be minimal. Study Design: Hospital Market Structure file (from Agency for Healthcare Research and Quality, available for years 2000 and 2003) was linked to Nationwide Inpatient Sample database. Appendectomy, carotid endarterectomy, bariatric surgery, radical prostatectomy, and pyloromyotomy were analyzed, after excluding patients with possible complications. Primary outcomes included total hospital charges. Primary independent variable was Herfindahl-Hirschman Index (HHI) calculated by the Agency for Healthcare Research and Quality for each hospital based on its patient-flow market. Higher HHI represents the presence of more dominant hospitals in the market or lower competition. Results: A total of 162,823 patients from 1,492 hospitals (85,791 appendectomies, 38,619 carotid endarterectomies, 18,383 bariatric operations, 16,784 radical prostatectomies, 3,246 pyloromyotomies) were analyzed. Single linear regression analyses demonstrated higher HHI was significantly associated with lower hospital gross charges in all cases. On multivariate analysis, a 1 percentage-point increase on HHI was associated with −$114 for appendectomy, −$163 for carotid endarterectomy, and −$193 for radical prostatectomy (all p ≤ 0.001), and were independent of hospital urbanicity, teaching status, and payer mix. In contrast, no association was found between competition and hospital costs. Conclusions: Higher level of hospital competition is associated with higher hospital gross charges, although competition intensity is not associated with hospital costs. These data are important as health policy makers consider possible cost-control measures. [Copyright &y& Elsevier]

Several recent research satellites carry self-calibrating multispectral imagers that can be used for calibrating operational imagers lacking complete self-calibrating capabilities. In particular, the visible (VIS, 0.65 μm) channels on operational meteorological satellites are generally calibrated before launch, but require vicarious calibration techniques to monitor the gains and offsets once they are in orbit. To ensure that the self-calibrating instruments are performing as expected, this paper examines the consistencies between the VIS channel (channel 1) reflectances of the Moderate Resolution Imaging Spectroradiometer (MODIS) instruments on the Terra and Aqua satellites and the version 5a and 6 reflectances of the Visible Infrared Scanner (VIRS) on the Tropical Rainfall Measuring Mission using a variety of techniques. These include comparisons of Terra and Aqua VIS radiances with coincident broadband shortwave radiances from the well-calibrated Clouds and the Earth’s Radiant Energy System (CERES), time series of deep convective cloud (DCC) albedos, and ray-matching intercalibrations between each of the three satellites. Time series of matched Terra and VIRS data, Aqua and VIRS data, and DCC reflected fluxes reveal that an older version (version 5a, ending in early 2004) of the VIRS calibration produced a highly stable record, while the latest version (version 6) appears to overestimate the sensor gain change by ∼1% yr-1 as the result of a manually induced gain adjustment. Comparisons with the CERES shortwave radiances unearthed a sudden change in the Terra MODIS calibration that caused a 1.17% decrease in the gain on 19 November 2003 that can be easily reversed. After correction for these manual adjustments, the trends in the VIRS and Terra channels are no greater than 0.1% yr-1. Although the results were more ambiguous, no statistically significant trends were found in the Aqua MODIS channel 1 gain. The Aqua radiances are 1% greater, on average, than their Terra counterparts, and after normalization are 4.6% greater than VIRS radiances, in agreement with theoretical calculations. The discrepancy between the two MODIS instruments should be taken into account to ensure consistency between parameters derived from them. With the adjustments, any of the three instruments can serve as references for calibrating other satellites. Monitoring of the calibrations continues in near–real time and the results are available via the World Wide Web. [ABSTRACT FROM AUTHOR]

We despread persistent contrails over the western Great Lakes during 9 October 2000 were examined using commercial flight data, coincident meteorological data, and satellite remote sensing data from several platforms. The data were analyzed to determine the atmospheric conditions under which the contrails formed and to measure several physical properties of the contrails, including areal coverage, spreading rates, fall speeds, and optical properties. Most of the contrails were located between 10.6 and 11.8 km in atmospheric conditions consistent with a modified form of the Appleman contrail formation theory. However, the Rapid Update Cycle-2 analyses have a dry bias in the upper-tropospheric relative humidity with respect to ice (RHI), as indicated by persistent contrail generation during the outbreak where RHI ≥ 85%. The model analyses show that synoptic-scale vertical velocities affect the formation of persistent contrails. Areal coverage by linear contrails peaked at 30 000 km2, but the maximum contrail-generated cirrus coverage was over twice as large. Contrail spreading rates averaged around 2.7 km h-1, and the contrails were visible in the 4-km Geostationary Operational Environmental Satellite (GOES) imagery approximately 1 h after formation. Contrail fall speed estimates were between 0.00 and 0.045 m s-1 based on observed contrail advection rates. Optical depth measurements ranged from 0.1 to 0.6, with consistent differences between remote sensing methods. Contrail formation density was roughly correlated with air traffic density after the effects of competing cloud coverage, humidity, and vertical velocity were considered. Improved tropospheric humidity measurements are needed for realistic simulations of contrail and cirrus development. [ABSTRACT FROM AUTHOR]

Index length of stay (LOS) and readmissions are viewed as important quality measures. However, these metrics represent competing demands as an inordinate reduction in LOS may lead to unplanned readmissions. We sought to assess the optimal LOS associated with the lowest 90-d readmission rate following discharge after common surgical procedures. This was a retrospective study relying on Tricare claims. We identified all eligible adult patients (18-64 y) receiving a series of common surgical procedures between 2006 and 2014. We used a generalized additive model with spline regression to determine the optimal LOS associated with the lowest 90-d risk of readmission. Ninety-day readmission rates varied from 6.03% to 34.69%. Most procedures exhibited a logit linear relationship, with the lowest risk of readmission evident on postoperative day-1 and increasing thereafter. Among the more invasive procedures (e.g., esophagectomy and radical cystectomy), a U-shaped relationship was realized, indicating that expedited discharge would increase the potential for readmission as would any extended hospital LOS. For these procedures, the ideal index LOS appeared to be 6-7 d for radical cystectomy and 12-13 d for esophagectomy. Our results support the practice of discharging patients as soon as clinically feasible after hip and knee arthroplasty, lumbar spine surgery, hernia repair, appendectomy, nephrectomy, and colectomy. Among esophagectomy or radical cystectomy, there is a well-defined optimal index admission period and discharge outside this window appears to be detrimental. Our results suggest that invasive procedures appear to possess a unique "signature" when it comes to optimal LOS. [ABSTRACT FROM AUTHOR]

This study aimed to assess tropical cloud properties predicted by Environment and Climate Change Canada's Global Environmental Multiscale (GEM) model when run with the Milbrandt–Yau double‐moment cloud microphysical scheme and one‐way nesting that culminated at a (∼300 km)2 inner domain with 0.25 km horizontal grid spacing. The assessment utilized satellite and in situ data collected during the High Ice Water Content (HIWC) and High Altitude Ice Crystals (HAIC) projects for a mesoscale convective system on 16 May 2015 over French Guiana. Data from CloudSat's cloud‐profiling radar and GOES‐13's imager were compared to data either simulated directly by GEM or produced by operating on GEM's cloud data with both the CFMIP (Cloud Feedback Model Intercomparison Project) Observation Simulator Package (COSP) instrument simulator and a three‐dimensional Monte Carlo solar radiative transfer model. In situ observations were made from research aircraft – Canada's National Research Council Convair‐580 and the French SAFIRE Falcon‐20 – whose flight paths were aligned with CloudSat's ground‐track. Spatial and temporal shifts of clouds simulated by GEM compared well to GOES‐13 imagery. There are, however, differences between simulated and observed amounts of high and low cloud. While GEM did well at predicting ranges of ice‐water content (IWC) near 11 km altitude (Falcon‐20), it produces too much graupel and snow near 7 km (Convair‐580). This produced large differences between CloudSat's and COSP‐generated radar reflectivities and two‐way attenuations. On the other hand, CloudSat's inferred values of IWC agree well with in situ samples at both altitudes. Generally, GEM's visible reflectances exceeded GOES‐13's on account of having produced too much low‐level liquid cloud. It is expected that GEM's disproportioning of cloud hydrometeors will improve once it includes a better representation of secondary ice production. The tropical convective clouds generate high ice‐water content at high altitude which can compromise the safe operation of commercial jet engines. This study evaluates the potential of a high‐resolution NWP model's capability of predicting the region with excessive ice‐water content as illustrated by Figure S1. The results of this evaluation have also led to further considerations of the role of secondary ice processes in the modelling of cloud properties for tropical regions. [ABSTRACT FROM AUTHOR]

Critical limb ischemia (CLI) is a frequent and major vascular problem and can lead to amputation and death despite surgical revascularization. Women have been shown to have 3 to 4 per cent lower revascularization rates for CLI compared with men as well as inferior outcomes. We hypothesize that this difference is a result of women being more likely admitted to low-volume hospitals, which in turn perform fewer revascularizations. Prospective cohort study. Data from the Nationwide Inpatient Sample 2007 to 2010 were used to identify admissions with primary International Classification of Diseases-9 codes for CLI (International Classification of Diseases-9 codes: 440.22, 440.23, 440.24, 707.1, 707.10-707.15, or 707.19). Hospitals were grouped in quintiles by annual revascularization procedures. Bivariate analyses were performed and multivariable logistic regression was used to analyze the odds of revascularization, amputation, and mortality while controlling for patient and hospital-level factors. Of 113,631 admissions, 54,370 (47.8%) were women, who were more likely admitted to low-volume hospitals (very low: 49.6% vs very high: 47.1%; P < 0.001). Revascularization rates were lower in women (31.6% vs 35.1%, P < 0.001) across all volume quintiles, whereas the difference was greatest in the use of open surgical revascularization (12.5% vs 16.0%, P < 0.001). In multivariable analysis, female gender [odds ratio (OR) 0.87, 95% confidence interval (CI) 0.83-0.92, P < 0.001] and very-low hospital volume (OR 0.21, 95% CI 0.17-0.26, P < 0.001) were both significantly associated with lower rates of revascularization. Women had lower odds of major amputation compared with men (OR 0.75, 95% CI 0.69-0.82, P < 0.001), whereas treatment in a very high-volume hospital was associated with increased odds for amputation (OR 1.37, 95% CI 1.09-1.73, P = 0.008). Neither gender nor hospital volume were independently associated with in-hospital mortality in the multivariable regression model. Women are more likely to be admitted to low-volume hospitals for treatment of CLI. Because of this, they are less likely to undergo revascularization, although they also had lower rates of major amputation. [ABSTRACT FROM AUTHOR]

Recent studies have found that ingestion of high mass concentrations of ice particles in regions of deep convective storms, with radar reflectivity considered safe for aircraft penetration, can adversely impact aircraft engine performance. Previous aviation industry studies have used the term high ice water content (HIWC) to define such conditions. Three airborne field campaigns were conducted in 2014 and 2015 to better understand how HIWC is distributed in deep convection, both as a function of altitude and proximity to convective updraft regions, and to facilitate development of new methods for detecting HIWC conditions, in addition to many other research and regulatory goals. This paper describes a prototype method for detecting HIWC conditions using geostationary (GEO) satellite imager data coupled with in situ total water content (TWC) observations collected during the flight campaigns. Three satellite-derived parameters were determined to be most useful for determining HIWC probability: (1) the horizontal proximity of the aircraft to the nearest overshooting convective updraft or textured anvil cloud, (2) tropopause-relative infrared brightness temperature, and (3) daytime-only cloud optical depth. Statistical fits between collocated TWC and GEO satellite parameters were used to determine the membership functions for the fuzzy logic derivation of HIWC probability. The products were demonstrated using data from several campaign flights and validated using a subset of the satellite-aircraft collocation database. The daytime HIWC probability was found to agree quite well with TWC time trends and identified extreme TWC events with high probability. Discrimination of HIWC was more challenging at night with IRonly information. The products show the greatest capability for discriminating TWC ≥0.5 gm-3. Product validation remains challenging due to vertical TWC uncertainties and the typically coarse spatio-temporal resolution of the GEO data. [ABSTRACT FROM AUTHOR]

Recent studies have found that flight through deep convective storms and ingestion of high mass concentrations of ice crystals, also known as high ice water content (HIWC), into aircraft engines can adversely impact aircraft engine performance. These aircraft engine icing events caused by HIWC have been documented during flight in weak reflectivity regions near convective updraft regions that do not appear threatening in onboard weather radar data. Three airborne field campaigns were conducted in 2014 and 2015 to better understand how HIWC is distributed in deep convection, both as a function of altitude and proximity to convective updraft regions, and to facilitate development of new methods for detecting HIWC conditions, in addition to many other research and regulatory goals. This paper describes a prototype method for detecting HIWC conditions using geostationary (GEO) satellite imager data coupled with in-situ total water content (TWC) observations collected during the flight campaigns. Three satellite-derived parameters were determined to be most useful for determining HIWC probability: 1) the horizontal proximity of the aircraft to the nearest overshooting convective updraft or textured anvil cloud, 2) tropopause-relative infrared brightness temperature, and 3) daytime-only cloud optical depth. Statistical fits between collocated TWC and GEO satellite parameters were used to determine the membership functions for the fuzzy logic derivation of HIWC probability. The products were demonstrated using data from several campaign flights and validated using a subset of the satellite-aircraft collocation database. The daytime HIWC probability was found to agree quite well with TWC time trends and identified extreme TWC events with high probability. Discrimination of HIWC was more challenging at night with IR-only information. The products show the greatest capability for discriminating TWC ≥ 0.5 g m-3. Product validation remains challenging due to vertical TWC uncertainties and the typically coarse spatio-temporal resolution of the GEO data. [ABSTRACT FROM AUTHOR]

Medical studies increasingly involve a large sample of independent clusters, where the cluster sizes are also large. Our motivating example from the 2010 Nationwide Inpatient Sample (NIS) has 8,001,068 patients and 1049 clusters, with average cluster size of 7627. Consistent parameter estimates can be obtained naively assuming independence, which are inefficient when the intra-cluster correlation (ICC) is high. Efficient generalized estimating equations (GEE) incorporate the ICC and sum all pairs of observations within a cluster when estimating the ICC. For the 2010 NIS, there are 92.6 billion pairs of observations, making summation of pairs computationally prohibitive. We propose a one-step GEE estimator that (1) matches the asymptotic efficiency of the fully iterated GEE; (2) uses a simpler formula to estimate the ICC that avoids summing over all pairs; and (3) completely avoids matrix multiplications and inversions. These three features make the proposed estimator much less computationally intensive, especially with large cluster sizes. A unique contribution of this article is that it expresses the GEE estimating equations incorporating the ICC as a simple sum of vectors and scalars. [ABSTRACT FROM PUBLISHER]

Background: This study seeks to quantify variation in healthcare utilization and per capita costs using system-defined geographic regions based on enrollee residence within the Military Health System (MHS).Methods: Data for fiscal years 2007 - 2010 were obtained from the Military Health System under a data sharing agreement with the Defense Health Agency (DHA). DHA manages all aspects of the Department of Defense Military Health System, including TRICARE. Adjusted rates were calculated for per capita costs and for two procedures with high interest to the MHS- back surgery and Cesarean sections for TRICARE Prime and Plus enrollees. Coefficients of variation (CoV) and interquartile ranges (IQR) were calculated and analyzed using residence catchment area as the geographic unit. Catchment areas anchored by a Military Treatment Facility (MTF) were compared to catchment areas not anchored by a MTF.Results: Variation, as measured by CoV, was 0.37 for back surgery and 0.13 for C-sections in FY 2010- comparable to rates documented in other healthcare systems. The 2010 CoV (and average cost) for per capita costs was 0.26 ($3,479.51). Procedure rates were generally lower and CoVs higher in regions anchored by a MTF compared with regions not anchored by a MTF, based on both system-wide comparisons and comparisons of neighboring areas.Conclusions: In spite of its centrally managed system and relatively healthy beneficiaries with very robust health benefits, the MHS is not immune to unexplained variation in utilization and cost of healthcare. [ABSTRACT FROM AUTHOR]

Background Liver transplantation centers are unevenly distributed within the Donor Service Areas (DSAs) of the United States. This study assessed how market competition and liver transplantation center density are associated with liver transplantation volume within individual DSAs. Study Design We conducted a retrospective cohort study of 53,156 adult liver transplants in 45 DSAs with 110 transplantation centers identified from the Scientific Registry of Transplant Recipients between 2003 and 2012. The following measures were derived annually for each DSA: market competition using the Herfindahl Hirschman Index, transplantation center density by the Average Nearest Neighbor method, liver quality by the Liver Donor Risk Index, and patient risk by the Model for End-Stage Liver Disease. A hierarchical mixed effects negative binomial regression model of the relationship between liver transplants and market factors was created annually. Patient and graft survival were investigated with a Cox proportional hazards model. Results Transplantation center density was associated with market competition (p < 0.0001), listings for organ transplantation (p < 0.0001), and Model for End-Stage Liver Disease at transplantation (p = 0.0005). More liver transplantation centers (incidence rate ratio [IRR] = 1.03; p = 0.04), greater market competition (IRR = 1.36; p = 0.02), increased listings (IRR = 1.14; p < 0.0001), more donors (IRR = 1.24; p < 0.0001), and higher Liver Donor Risk Index (IRR = 3.35; p < 0.0001) were associated with more transplants. No market variables were associated with increased mortality after transplantation. Conclusions After controlling for demographic and market factors, a greater concentration of centers was associated with more liver transplants without impacting overall survival. These results warrant additional investigation into the relationship between geospatial factors and liver transplantation volume with consideration for the optimization of scarce resources. [ABSTRACT FROM AUTHOR]

Background Failure-to-rescue (FTR or death after postoperative complication) is thought to explain surgical mortality excesses across hospitals, and FTR is an emerging performance measure and target for quality improvement. We compared the FTR population to preoperatively identifiable subpopulations for their potential to close the mortality gap between lowest- and highest-mortality hospitals. Study Design Patients undergoing small bowel resection, pancreatectomy, colorectal resection, open abdominal aortic aneurysm repair, lower extremity arterial bypass, and nephrectomy were identified in the 2007 to 2011 Nationwide Inpatient Sample. Lowest- and highest-mortality hospitals were defined using risk- and reliability-adjusted mortality quintiles. Five target subpopulations were established a priori: the FTR population, predicted high-mortality risk (predicted highest-risk quintile), emergency surgery, elderly (>75 years old), and diabetic patients. Results Across the lowest mortality quintile (n = 282 hospitals, 56,893 patients) and highest-mortality quintile (282 hospitals, 45,784 patients), respectively, the size of target subpopulations varied only for the FTR population (20.2% vs 22.4%, p = 0.002) but not for other subpopulations. Variation in mortality rates across lowest- and highest-mortality hospitals was greatest for the high-mortality risk (7.5% vs 20.2%, p < 0.0001) and FTR subpopulations (7.8% vs 18.9%, p < 0.0001). The FTR and high-risk populations had comparable sensitivity (81% and 75%) and positive predictive value (19% and 20%, respectively) for mortality. In Monte Carlo simulations, the mortality gap between the lowest- and highest-mortality hospitals was reduced by nearly 75% when targeting the FTR population or the high-risk population, 78% for the emergency surgery population, but less for elderly (51%) and diabetic (17%) populations. Conclusions Preoperatively identifiable patients with high estimated mortality risk may be preferable to the FTR population as a target for surgical mortality reduction. [ABSTRACT FROM AUTHOR]

Background Performance measurement has become central to surgical practice. We systematically reviewed all endorsed performance measures from the National Quality Forum, the national clearing house for performance measures in health care, to identify measures relevant to surgical practice and describe measure stewardship, measure types, and identify gaps in measurement. Study Design Performance measures current to June 2014 were categorized by denominator statement as either assessing surgical practice in specific or as part of a mixed medical and surgical population. Measures were further classified by surgical specialty, Donabedian measure type, patients, disease and events targeted, reporting eligibility, and measure stewards. Results Of 637 measures, 123 measures assessed surgical performance in specific and 123 assessed surgical performance in aggregate. Physician societies (51 of 123, 41.5%) were more common than government agencies (32 of 123, 26.0%) among measure stewards for surgical measures, in particular, the Society for Thoracic Surgery (n = 32). Outcomes measures rather than process measures were common among surgical measures (62 of 123, 50.4%) compared with aggregate medical/surgical measures (46 of 123, 37.4%). Among outcomes measures, death alone was the most commonly specified outcome (24 of 62, 38.7%). Only 1 surgical measure addressed patient-centered care and only 1 measure addressed hospital readmission. We found 7 current surgical measures eligible for value-based purchasing. Conclusions Surgical society stewards and outcomes measure types, particularly for cardiac surgery, were well represented in the National Quality Forum. Measures addressing patient-centered outcomes and the value of surgical decision-making were not well represented and may be suitable targets for measure innovation. [ABSTRACT FROM AUTHOR]

Background: Surgical patients and their physicians currently have tools to provide individualized prognostication for morbidity and mortality. For improved shared decision making, formal prediction of patient-centered outcomes is necessary. We derived and validated a simple, interview-based method to predict discharge home after surgery. Study Design: We used the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) Patient User File for 2011. Derivation in general and vascular surgery patients undergoing inpatient surgery was completed using serial multiple logistic regression. Validation was performed within multiple surgical specialties. Results: The derivation cohort included 88,068 patients, of whom 11,771 (13.4%) were not discharged home. The derived Home Calculator had excellent discrimination (c-statistic = 0.864) using 4 variables: age, American Society of Anesthesiologists' performance status, elective surgery, and preadmission residence. Validation cohorts had varying rates of home discharge as follows: general (63,826 of 71,591, 89.2%), vascular (12,319 of 16,102, 76.5%), gynecologic (16,603 of 17,005, 97.6%), urologic (13,662 of 14,435, 94.6%), orthopaedic (12,000 of 19,514, 61.5%), thoracic (4,467 of 5,092, 87.7%). The Home Calculator provided good to excellent discrimination in validation cohorts: general (c = 0.866), vascular (c = 0.800), gynecologic (c = 0.793), urologic (c = 0.814), orthopaedic (c = 0.876), and thoracic (c = 0.800). Comparable discrimination was demonstrated in sensitivity analyses in surgical patients admitted exclusively from home. Conclusions: We derived and validated a simple Home Calculator that reliably predicts discharge to home after surgery and may be useful when counseling patients about postoperative course. Patient-centered tools such as this may allow physicians to better prepare patients and families for surgery and the recovery process. [Copyright &y& Elsevier]

BACKGROUND: We hypothesized that human perivascular and subcutaneous adipose tissues hold distinct phenotypic signatures. We also evaluated the impact of clinical parameters on the adipose phenotype. Our overall goal is to understand. the determinants of adipose biology so that this tissue can be manipulated therapeutically to lessen peripheral vascular disease. METHODS: Perivascular and subcutaneous adipose tissues were collected from patients undergoing lower-extremity amputation (n = 27) and protein assayed for proinflammatory mediators (ie, interleukin 6, interleukin 8, leptin, tumor necrosis factor α, monocyte chemoattractant protein-1 , and resistin), atheroprotective adiponectin, and the fibrinolysis inhibitor plasminogen activator inhibitor-1. RESULTS: Leptin (2.7-fold, P = .015), TNF-α (2.2-fold, P = .013), MCP-1 (1.5-fold, P = .047), and adiponectin (1.8-fold, P = .004) were more abundant in subcutaneous vs perivascular adipose tissue. Age positively correlated with perivascular adipose tissue PAl-I expression (β = .64, P = .042), and hyperlipidemia negatively correlated with perivascular adiponectin (β = -1.18, P = .039). CONCLUSIONS: Human perivascular and subcutaneous adipose tissues hold distinct phenotypic signatures. In amputation patients, the subcutaneous adipose tissue proinflammatory phenotype was relatively attenuated in perivascular adipose tissue. [ABSTRACT FROM AUTHOR]

An algorithm is developed to determine the flight icing threat to aircraft utilizing quantitative information on clouds derived from meteorological satellite data as input. Algorithm inputs include the satellite-derived cloud-top temperature, thermodynamic phase, water path, and effective droplet size. The icing-top and -base altitude boundaries are estimated from the satellite-derived cloud-top and -base altitudes using the freezing level obtained from numerical weather analyses or a lapse-rate approach. The product is available at the nominal resolution of the satellite pixel. Aircraft pilot reports (PIREPs) over the United States and southern Canada provide direct observations of icing and are used extensively in the algorithm development and validation on the basis of correlations with Geostationary Operational Environmental Satellite imager data. Verification studies using PIREPs, Tropospheric Airborne Meteorological Data Reporting, and NASA Icing Remote Sensing System data indicate that the satellite algorithm performs reasonably well, particularly during the daytime. The algorithm is currently being run routinely using data taken from a variety of satellites across the globe and is providing useful information on icing conditions at high spatial and temporal resolutions that are unavailable from any other source. [ABSTRACT FROM AUTHOR]

Cloud properties were retrieved by applying the Clouds and Earth's Radiant Energy System (CERES) project Edition-2 algorithms to 3.5 years of Tropical Rainfall Measuring Mission Visible and Infrared Scanner data and 5.5 and 8 years of MODerate Resolution Imaging Spectroradiometer (MODIS) data from Aqua and Terra, respectively. The cloud products are consistent quantitatively from all three imagers; the greatest discrepancies occur over ice-covered surfaces. The retrieved cloud cover (\sim59%) is divided equally between liquid and ice clouds. Global mean cloud effective heights, optical depth, effective particle sizes, and water paths are 2.5 km, 9.9, 12.9 \mu\m, and 80 \g\cdot \m^-2, respectively, for liquid clouds and 8.3 km, 12.7, 52.2 \mu\m, and 230 \g\cdot \m^-2 for ice clouds. Cloud droplet effective radius is greater over ocean than land and has a pronounced seasonal cycle over southern oceans. Comparisons with independent measurements from surface sites, the Ice Cloud and Land Elevation Satellite, and the Aqua Advanced Microwave Scanning Radiometer–Earth Observing System are used to evaluate the results. The mean CERES and MODIS Atmosphere Science Team cloud properties have many similarities but exhibit large discrepancies in certain parameters due to differences in the algorithms and the number of unretrieved cloud pixels. Problem areas in the CERES algorithms are identified and discussed. [ABSTRACT FROM AUTHOR]

Laser beams emitted from the Geoscience Laser Altimeter System (GLAS), as well as other spaceborne laser instruments, can only penetrate clouds to a limit of a few optical depths. As a result, only optical depths of thinner clouds (< about 3 for GLAS) are retrieved from the reflected lidar signal. This paper presents a comprehensive study of possible retrievals of optical depth of thick clouds using solar background light and treating GLAS as a solar radiometer. To do so one must first calibrate the reflected solar radiation received by the photon-counting detectors of the GLAS 532-nm channel, the primary channel for atmospheric products. Solar background radiation is regarded as a noise to be subtracted in the retrieval process of the lidar products. However, once calibrated, it becomes a signal that can be used in studying the properties of optically thick clouds. In this paper, three calibration methods are presented: (i) calibration with coincident airborne and GLAS observations, (ii) calibration with coincident Geostationary Operational Environmental Satellite (GOES) and GLAS observations of deep convective clouds, and (iii) calibration from first principles using optical depth of thin water clouds over ocean retrieved by GLAS active remote sensing. Results from the three methods agree well with each other. Cloud optical depth (COD) is retrieved from the calibrated solar background signal using a one-channel retrieval. Comparison with COD retrieved from GOES during GLAS overpasses shows that the average difference between the two retrievals is 24%. As an example, the COD values retrieved from GLAS solar background are illustrated for a marine stratocumulus cloud field that is too thick to be penetrated by the GLAS laser. Based on this study, optical depths for thick clouds will be provided as a supplementary product to the existing operational GLAS cloud products in future GLAS data releases. [ABSTRACT FROM AUTHOR]

The restenosis rates of 5% to 15% have been reported after carotid endarterectomy (CEA). We undertook this investigation to determine whether the routine practice of carotid artery patch closure and intraoperative completion duplex ultrasonography would result in lower rates of carotid restenosis after CEA. All consecutive carotid endarterectomies performed between 2000 and 2004 at a single institution were reviewed retrospectively. Patients underwent CEA using a longitudinal arteriotomy, followed by routine patching and intraoperative completion duplex ultrasonography. Only patients with at least one postoperative duplex scan performed at a minimum of 180 days after CEA were included. During the 5-year study period, 407 consecutive carotid endarterectomies were performed, with a combined 30-day stroke and mortality rate of 2.5%; 217 patients (53%) had one or more duplex ultrasound examinations performed at least 180 days after CEA. The mean follow-up duration was 692 days. Of the patients who underwent intraoperative intervention based on the results of the completion duplex study, none experienced restenosis, stroke, or death. CEA that is performed with routine patching and intraoperative duplex completion ultrasonography is a safe, durable operation with restenosis rates below those commonly reported. [ABSTRACT FROM AUTHOR]

Parameters derived from satellite observations depend on the quality of the calibration method applied to the raw satellite radiance measurements. This study investigates the sensitivity of absolute reflectance, derived cloud cover, and estimated surface shortwave (SW) downward fluxes to two different calibration methods for the visible sensor aboard the eighth Geostationary Operational Environmental Satellite (GOES-8). The first method was developed at NOAA's National Environmental Satellite, Data, and Information Service (NESDIS), and the second at the NASA Langley Research Center. Differences in visible reflectance ranged from -0.5% to 3%. The average difference in monthly mean cloud amount was ∼3%, and the average difference in monthly mean shortwave downward flux was 5 W m-2. Differences in bias and rms of the SW fluxes when evaluated against ground station measurements were less than 3 W m-2. Neither calibration method was shown to consistently outperform the other. This evaluation yields an estimate of the errors in fluxes that can be attributed to calibration. [ABSTRACT FROM AUTHOR]

Introduction: Analysis of large complex survey databases is an important research tool for health services researchers in Surgery. Missing data elements are challenging as reasons they are missing are multi-factorial, especially variables with multiple categories such as race. We simulated missing data for race and analyzed the bias from five missing data methods used in predicting major amputation in patients with critical limb ischemia (CLI). Methods: Discharges with fully observed data containing lower extremity revascularization or major amputation and CLI were selected from the 2003-2007 Nationwide Inpatient Sample, a complex survey database (weighted N=684,057). Considering random and non-random missing data schemes, we simulated missing data for race to compare five missing data methods (complete case analysis (CCA), missing indicator variable (MIV), single imputation with mean frequencies, re-weighted estimating equations (RWEEs), and multiple imputation). Bias was determined by comparing mean regression coefficients estimated from 100 simulated datasets (B_miss) to those estimated from the fully observed dataset (B_full), with relative bias calculated as (B_full–B_miss/B_full)*100%. Results: Our results demonstrate that RWEEs produce the least biased and MIV the most biased coefficients. CCA, single imputation, and multiple imputation resulted in moderate bias. Sensitivity analysis demonstrated that optimal method choice depends on quantity and type of missing data encountered. Conclusions: Missing data is an important analytical topic in research with large databases. RWEEs are flexible and provided the least biased coefficients. The commonly used MIV method introduces the most bias and should be used with caution. We present empirical evidence to guide method selection for handling missing data. [ABSTRACT FROM AUTHOR]