Adjusting for bias introduced by instrumental variable estimation in the Cox Proportional Hazards Model

Instrumental variable (IV) methods are widely used for estimating average treatment effects in the presence of unmeasured confounders. However, the capability of existing IV procedures, and most notably the two-stage residual inclusion (2SRI) procedure recommended for use in nonlinear contexts, to account for unmeasured confounders in the Cox proportional hazard model is unclear. We show that instrumenting an endogenous treatment induces an unmeasured covariate, referred to as an individual frailty in survival analysis parlance, which if not accounted for leads to bias. We propose a new procedure that augments 2SRI with an individual frailty and prove that it is consistent under certain conditions. The finite sample-size behavior is studied across a broad set of conditions via Monte Carlo simulations. Finally, the proposed methodology is used to estimate the average effect of carotid endarterectomy versus carotid artery stenting on the mortality of patients suffering from carotid artery disease. Results suggest that the 2SRI-frailty estimator generally reduces the bias of both point and interval estimators compared to traditional 2SRI.Comment: 27 pages, 8 figures, 4 table

Patient-predicted sleep position vs. HST data: a tendency to underestimate supine sleep

Purpose The purpose of this study is to measure people’s accuracy when they estimate what proportion of their nightly sleep at home is supine vs. non-supine. Methods A series of patients referred for obstructive sleep apnea (OSA) evaluation were asked if they Bknew with confidence^ how they slept with regard to their body position. BYes^ responders were then asked to estimate what percentage of their sleep was supine vs. non-supine. This value was compared with the actual proportion of supine vs. non-supine sleep that they exhibited in a home sleep test (HST) that followed. Results We obtained data from 49 subjects who expressed that they Bknew with confidence^ how they sleep in terms of body position. Subjects in aggregate underestimated their proportion of supine sleep by 21.6% (p \u3c .001). Thirty-nine subjects (80%) slept supine more in the HST whereas 8 (16%) slept supine less compared to their pre-test estimates. Using a common classification of OSA severity, 9 subjects (18%) demonstrated a more severe degree of OSA than would have occurred had they slept as they had predicted. Conclusions Subjects in this study frequently underestimated their proportion of supine sleep compared to values measured in an HST. Because of the increased supine sleep they exhibited, the severity of their OSAwas often greater in the test than it would have been had the subjects slept as they predicted

Characterizing rescue performance in a tertiary care medical center: a systems approach to provide management decision support

Background: Allocation of limited resources to improve quality, patient safety, and outcomes is a decision-making challenge health care leaders face every day. While much valuable health care management research has concentrated on administrative data analysis, this approach often falls short of providing actionable information essential for effective management of specific system implementations and complex systems. This comprehensive performance analysis of a hospital-wide system illustrates application of various analysis approaches to support understanding specific system behaviors and identify leverage points for improvement. The study focuses on performance of a hospital rescue system supporting early recognition and response to patient deterioration, which is essential to reduce preventable inpatient deaths. Methods: Retrospective analysis of tertiary care hospital inpatient and rescue data was conducted using a systems analysis approach to characterize: patient demographics; rescue activation types and locations; temporal patterns of activation; and associations of patient factors, including complications, with post-rescue care disposition and outcomes. Results: Increases in bedside consultations (20% per year) were found with increased rescue activations during periods of resource limitations and changes (e.g., shift changes, weekends). Cardiac arrest, respiratory failure, and sepsis complications present the highest risk for rescue and death. Distributions of incidence of rescue and death by day of patient stay may suggest opportunities for earlier recognition. Conclusions: Specific findings highlight the potential of using rescue-related risk and targeted resource deployment strategies to improve early detection of deterioration. The approach and methods applied can be used by other institutions to understand performance and allow rational incremental improvements to complex care delivery systems

Consistency of Hemoglobin A1c Testing and Cardiovascular Outcomes in Medicare Patients With Diabetes

Background: Annual hemoglobin A1c testing is recommended for patients with diabetes mellitus. However, it is unknown how consistently patients with diabetes mellitus receive hemoglobin A1c testing over time, or whether testing consistency is associated with adverse cardiovascular outcomes. Methods and Results: We identified 1 574 415 Medicare patients (2002–2012) with diabetes mellitus over the age of 65. We followed each patient for a minimum of 3 years to determine their consistency in hemoglobin A1C testing, using 3 categories: low (testing in 0 or 1 of 3 years), medium (testing in 2 of 3 years), and high (testing in all 3 years). In unweighted and inverse propensity‐weighted cohorts, we examined associations between testing consistency and major adverse cardiovascular events, defined as death, myocardial infarction, stroke, amputation, or the need for leg revascularization. Overall, 70.2% of patients received high‐consistency testing, 17.6% of patients received medium‐consistency testing, and 12.2% of patients received low‐consistency testing. When compared to high‐consistency testing, low‐consistency testing was associated with a higher risk of adverse cardiovascular events or death in unweighted analyses (hazard ratio [HR]=1.21; 95% CI, 1.20–1.23; P\u3c0.001), inverse propensity‐weighted analyses (HR=1.16; 95% CI, 1.15–1.17; P\u3c0.001), and weighted analyses limited to patients who had at least 4 physician visits annually (HR=1.15; 95% CI, 1.15–1.16; P\u3c0.001). Less‐consistent testing was associated with worse results for each cardiovascular outcome and in analyses using all years as the exposure. Conclusions: Consistent annual hemoglobin A1c testing is associated with fewer adverse cardiovascular outcomes in this observational cohort of Medicare patients of diabetes mellitus

Growing impact of restenosis on the surgical treatment of peripheral arterial disease

BACKGROUND: Patients with peripheral arterial disease often experience treatment failure from restenosis at the site of a prior peripheral endovascular intervention (PVI) or lower extremity bypass (LEB). The impact of these treatment failures on the utilization and outcomes of secondary interventions is poorly understood. METHODS AND RESULTS: In our regional vascular quality improvement collaborative, we compared 2350 patients undergoing primary infrainguinal LEB with 1154 patients undergoing secondary infrainguinal LEB (LEB performed after previous revascularization in the index limb) between 2003 and 2011. The proportion of patients undergoing secondary LEB increased by 72% during the study period (22% of all LEBs in 2003 to 38% in 2011, P\u3c0.001). In-hospital outcomes, such as myocardial infarction, death, and amputation, were similar between primary and secondary LEB groups. However, in both crude and propensity-weighted analyses, secondary LEB was associated with significantly inferior 1-year outcomes, including major adverse limb event-free survival (composite of death, new bypass graft, surgical bypass graft revision, thrombectomy/thrombolysis, or above-ankle amputation; Secondary LEB MALE-free survival = 61.6% vs primary LEB MALE-free survival = 67.5%, P=0.002) and reintervention or amputation-free survival (composite of death, reintervention, or above-ankle amputation; Secondary LEB RAO-free survival = 58.9% vs Primary LEB RAO-free survival 64.1%, P=0.003). Inferior outcomes for secondary LEB were observed regardless of the prior failed treatment type (PVI or LEB). CONCLUSIONS: In an era of increasing utilization of PVI, a growing proportion of patients undergo LEB in the setting of a prior failed PVI or surgical bypass. When caring for patients with peripheral arterial disease, physicians should recognize that first treatment failure (PVI or LEB) affects the success of subsequent revascularizations

Incomplete Polyp Resection During Colonoscopy—Results of the Complete Adenoma Resection (CARE) Study

Although the adenoma detection rate is used as a measure of colonoscopy quality, there are limited data on the quality of endoscopic resection of detected adenomas. We determined the rate of incompletely resected neoplastic polyps in clinical practice.We performed a prospective study on 1427 patients who underwent colonoscopy at 2 medical centers and had at least 1 nonpedunculated polyp (5-20 mm). After polyp removal was considered complete macroscopically, biopsies were obtained from the resection margin. The main outcome was the percentage of incompletely resected neoplastic polyps (incomplete resection rate [IRR]) determined by the presence of neoplastic tissue in post-polypectomy biopsies. Associations between IRR and polyp size, morphology, histology, and endoscopist were assessed by regression analysis. Of 346 neoplastic polyps (269 patients; 84.0% men; mean age, 63.4 years) removed by 11 gastroenterologists, 10.1% were incompletely resected. IRR increased with polyp size and was significantly higher for large (10-20 mm) than small (5-9 mm) neoplastic polyps (17.3% vs 6.8%; relative risk = 2.1), and for sessile serrated adenomas/polyps than for conventional adenomas (31.0% vs 7.2%; relative risk = 3.7). The IRR for endoscopists with at least 20 polypectomies ranged from 6.5% to 22.7%; there was a 3.4-fold difference between the highest and lowest IRR after adjusting for size and sessile serrated histology. Neoplastic polyps are often incompletely resected, and the rate of incomplete resection varies broadly among endoscopists. Incomplete resection might contribute to the development of colon cancers after colonoscopy (interval cancers). Efforts are needed to ensure complete resection, especially of larger lesions

Disentangling a group of lensed submm galaxies at z∼ 2.9

MS0451.6−0305 is a rich galaxy cluster whose strong lensing is particularly prominent at submm wavelengths. We combine new Submillimetre Common-User Bolometer Array (SCUBA)-2 data with imaging from Herschel Spectral and Photometric Imaging Receiver (SPIRE) and PACS and Hubble Space Telescope in order to try to understand the nature of the sources being lensed. In the region of the ‘giant submm arc', we uncover seven multiply imaged galaxies (up from the previously known four), of which six are found to be at a redshift of z∼2.9, and possibly constitute an interacting system. Using a novel forward-modelling approach, we are able to simultaneously deblend and fit spectral energy distributions to the individual galaxies that contribute to the giant submm arc, constraining their dust temperatures, far-infrared luminosities, and star formation rates (SFRs). The submm arc first identified by SCUBA can now be seen to be composed of at least five distinct sources, four of these within a galaxy group at z∼2.9. Only a handful of lensed galaxy groups at this redshift are expected on the sky, and thus this is a unique opportunity for studying such systems in detail. The total unlensed luminosity for this galaxy group is (3.1±0.3)×1012 L⊙, which gives an unlensed SFR of (450±50) M⊙yr−1. This finding suggests that submm source multiplicity, due to physically associated groupings as opposed to chance alignment, extends to fainter flux densities than previously discovered. Many of these systems may also host optical companions undetected in the submm, as is the case her

Evaluation of ACCMIP Outgoing Longwave Radiation from Tropospheric Ozone Using TES Satellite Observations.

We use simultaneous observations of tropospheric ozone and outgoing longwave radiation (OLR) sensitivity to tropospheric ozone from the Tropospheric Emission Spectrometer (TES) to evaluate model tropospheric ozone and its effect on OLR simulated by a suite of chemistry-climate models that participated in the Atmospheric Chemistry and Climate Model Intercomparison Project (ACCMIP). The ensemble mean of ACCMIP models show a persistent but modest tropospheric ozone low bias (5-20 ppb) in the Southern Hemisphere (SH) and modest high bias (5-10 ppb) in the Northern Hemisphere (NH) relative to TES ozone for 2005-2010. These ozone biases have a significant impact on the OLR. Using TES instantaneous radiative kernels (IRK), we show that the ACCMIP ensemble mean tropospheric ozone low bias leads up to 120mW/ sq. m OLR high bias locally but zonally compensating errors reduce the global OLR high bias to 39+/- 41mW/ sq. m relative to TES data. We show that there is a correlation (Sq. R = 0.59) between the magnitude of the ACCMIP OLR bias and the deviation of the ACCMIP preindustrial to present day (1750-2010) ozone radiative forcing (RF) from the ensemble ozone RF mean. However, this correlation is driven primarily by models whose absolute OLR bias from tropospheric ozone exceeds 100mW/ sq. m. Removing these models leads to a mean ozone radiative forcing of 394+/- 42mW/ sq. m. The mean is about the same and the standard deviation is about 30% lower than an ensemble ozone RF of 384 +/- 60mW/ sq. m derived from 14 of the 16 ACCMIP models reported in a companion ACCMIP study. These results point towards a profitable direction of combining satellite observations and chemistry-climate model simulations to reduce uncertainty in ozone radiative forcing

How does study quality affect the results of a diagnostic meta-analysis?

Background: The use of systematic literature review to inform evidence based practice in diagnostics is rapidly expanding. Although the primary diagnostic literature is extensive, studies are often of low methodological quality or poorly reported. There has been no rigorously evaluated, evidence based tool to assess the methodological quality of diagnostic studies. The primary objective of this study was to determine the extent to which variations in the quality of primary studies impact the results of a diagnostic meta-analysis and whether this differs with diagnostic test type. A secondary objective was to contribute to the evaluation of QUADAS, an evidence-based tool for the assessment of quality in diagnostic accuracy studies. Methods: This study was conducted as part of large systematic review of tests used in the diagnosis and further investigation of urinary tract infection (UTI) in children. All studies included in this review were assessed using QUADAS, an evidence-based tool for the assessment of quality in systematic reviews of diagnostic accuracy studies. The impact of individual components of QUADAS on a summary measure of diagnostic accuracy was investigated using regression analysis. The review divided the diagnosis and further investigation of UTI into the following three clinical stages: diagnosis of UTI, localisation of infection, and further investigation of the UTI. Each stage used different types of diagnostic test, which were considered to involve different quality concerns. Results: Many of the studies included in our review were poorly reported. The proportion of QUADAS items fulfilled was similar for studies in different sections of the review. However, as might be expected, the individual items fulfilled differed between the three clinical stages. Regression analysis found that different items showed a strong association with test performance for the different tests evaluated. These differences were observed both within and between the three clinical stages assessed by the review. The results of regression analyses were also affected by whether or not a weighting (by sample size) was applied. Our analysis was severely limited by the completeness of reporting and the differences between the index tests evaluated and the reference standards used to confirm diagnoses in the primary studies. Few tests were evaluated by sufficient studies to allow meaningful use of meta-analytic pooling and investigation of heterogeneity. This meant that further analysis to investigate heterogeneity could only be undertaken using a subset of studies, and that the findings are open to various interpretations. Conclusion: Further work is needed to investigate the influence of methodological quality on the results of diagnostic meta-analyses. Large data sets of well-reported primary studies are needed to address this question. Without significant improvements in the completeness of reporting of primary studies, progress in this area will be limited