Power loss due to testing association between covariate-adjusted traits and genetic variants

Multiple linear regression is commonly used to test for association between genetic variants and continuous traits and estimate genetic effect sizes. Confounding variables are controlled for by including them as additional covariates. An alternative technique that is increasingly used is to regress out covariates from the raw trait and then perform regression analysis with only the genetic variants included as predictors. In the case of single-variant analysis, this adjusted trait regression (ATR) technique is known to be less powerful than the traditional technique when the genetic variant is correlated with the covariates We extend previous results for single-variant tests by deriving exact relationships between the single-variant score, Wald, likelihood-ratio, and F test statistics and their ATR analogs. We also derive the asymptotic power of ATR analogs of the multiple-variant score and burden tests. We show that the maximum power loss of the ATR analog of the multiple-variant score test is completely characterized by the canonical correlations between the set of genetic variants and the set of covariates. Further, we show that for both single- and multiple-variant tests, the power loss for ATR analogs increases with increasing stringency of Type 1 error control () and increasing correlation (or canonical correlations) between the genetic variant (or multiple variants) and covariates. We recommend using ATR only when maximum canonical correlation between variants and covariates is low, as is typically true.     

Shared decision-making for the management of small renal masses: Development and acceptability testing of a novel patient decision aid

IntroductionShared decision-making incorporates patients’ values and preferences to achieve high-quality decisions. The objective of this study was to develop an acceptable patient decision aid to facilitate shared decision-making for the management of small renal masses (SRMs).MethodsThe International Patient Decision Aids Standards were used to guide an evidence-based development process. Management options included active surveillance, thermal ablation, partial nephrectomy, and radical nephrectomy. A literature review was performed to provide incidence rates for outcomes of each option. Once a prototype was complete, alpha-testing was performed using a 10-question survey to assess acceptability with patients, patient advocates, urologists, and methodological experts. The primary outcome was acceptability of the decision aid.ResultsA novel patient decision aid was created to facilitate shared decision-making for the management of SRMs. Acceptability testing was performed with 20 patients, 10 urologists, two patient advocates, and one methodological expert. Responders indicated the decision aid was appropriate in length (82%, 27/33), well-balanced (82%, 27/33), and had language that was easy to follow (94%, 31/33). All patient responders felt the decision aid would have been helpful during their consultation and would recommend the decision aid for future patients (100%, 20/20). Most urologists reported they intend to use the decision aid (90%, 9/10).ConclusionsA novel patient decision aid was created to facilitate shared decision-making for management of SRMs. This clinical tool was acceptable with patients, patient advocates, and urologists and is freely available at: https://decisionaid.ohri.ca/decaids.html.     

Prolonged mechanical ventilation after cardiac surgery: substudy of the Transfusion Requirements in Cardiac Surgery III trial

Purpose

Prolonged mechanical ventilation (MV) is a major complication following cardiac surgery. We conducted a secondary analysis of the Transfusion Requirements in Cardiac Surgery (TRICTS) III trial to describe MV duration, identify factors associated with prolonged MV, and examine associations of prolonged MV with mortality and complications.

Methods

Four thousand, eight hundred and nine participants undergoing cardiac surgery at 71 hospitals worldwide were included. Prolonged MV was defined based on the Society of Thoracic Surgeons definition as MV lasting 24 hr or longer. Adjusted associations of patient and surgical factors with prolonged MV were examined using multivariable logistic regression. Associations of prolonged MV with complications were assessed using odds ratios, and adjusted associations between prolonged MV and mortality were evaluated using multinomial regression. Associations of shorter durations of MV with survival and complications were explored.

Results

Prolonged MV occurred in 15% (725/4,809) of participants. Prolonged MV was associated with surgical factors indicative of complexity, such as previous cardiac surgery, cardiopulmonary bypass duration, and separation attempts; and patient factors such as critical preoperative state, left ventricular impairment, renal failure, and pulmonary hypertension. Prolonged MV was associated with perioperative but not long-term complications. After risk adjustment, prolonged MV was associated with perioperative mortality; its association with long-term mortality among survivors was weaker. Shorter durations of MV were not associated with increased risk of mortality or complications.

Conclusion

In this substudy of the TRICS III trial, prolonged MV was common after cardiac surgery and was associated with patient and surgical risk factors. Although prolonged MV showed strong associations with perioperative complications and mortality, it was not associated with long-term complications and had weaker association with long-term mortality among survivors.

Study registration

www.ClinicalTrials.gov (NCT02042898); registered 23 January 2014. This is a substudy of the Transfusion Requirements in Cardiac Surgery (TRICS) III trial.

     

A second wave of COVID-19 in Cook County: What lessons can be applied?

During the ongoing public health crisis, many agencies are reporting COVID-19 health outcome information based on the overall population. This practice can lead to misleading results and underestimation of high risk areas. To gain a better understanding of spatial and temporal distribution of COVID-19 deaths; the long term care facility (LTCF) and household population (HP) deaths must be used. This approach allows us to better discern high risk areas and provides policy makers with reliable information for community engagement and mitigation strategies. By focusing on high-risk LTCFs and residential areas, protective measures can be implemented to minimize COVID-19 spread and subsequent mortality.  These areas should be a high priority target when COVID-19 vaccines become available

During the current public health crisis, many agencies and media outlets are reporting COVID-19 health outcome information based on the overall population of Cook County. As we have demonstrated, overall COVID-19 case counts and mortality can be misleading (details in >Story Map 1). Moreover, they offer little guidance for delivering public health interventions to high risk populations, a critical need during this second and potentially more devastating wave of the pandemic. The University of Illinois Chicago School of Public Health’s Public Health Geographic Information System Program (UIC-SPH-PHGIS) and Purdue research team has been examining spatial and temporal patterns of COVID-19 mortality with a focus on the significant loss of life from COVID-19 among Long-Term Care Facility (LTCF) residents in contrast to mortality in the community among residents of private households (non-LTCF; referred to as household population, HP). The goals of the study are:

• Improve the accuracy of commonly quoted COVID-19 mortality indicators;
• Gain a better understanding of spatial and temporal distribution of COVID-19 deaths;
• Examine the role of race, ethnicity, and socioeconomic status in COVID-19 mortality;
• Identify population and organizational parameters that can inform strategies for public health interventions.

Prioritizing the allocation of resources based on reliable information is a prerequisite of a successful mitigation strategy and immunization plan. Findings from our research have significant practical implications. The state and federal government face a series of policy decisions both due to the recent surge in positive cases and, when the time comes, the need to rationalize distribution of vaccines to high priority groups beyond healthcare workers and nursing home residents in critical areas. The research team seeks to modify prevailing practices in order to derive reliable information that guides policy decisions. At this stage of the study, we identified high-risk LTCFs and residential areas (HP) of Cook County from readily available, real-time mortality data.     

Comparison of Patch Materials for Pulmonary Artery Reconstruction

Graphical abstract summarizing the overall results of our study comparing reintervention for a main or central branch pulmonary artery reconstruction site and various patch materials. Autologous pericardium was associate with the lowest reintervention and was free. Multivariable analysis demonstrated lack of superiority of homograft branch patch, which clearly has a much higher cost.

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Dose optimization of moxifloxacin and linezolid against tuberculosis using mathematical modeling and simulation

Introduction

There is an urgent need for new anti-tuberculosis (TB) drugs and optimization of current TB treatment. Moxifloxacin and linezolid are valuable options for the treatment of drug-resistant TB; however, it is crucial to find a dose at which these drugs not only show high efficacy but also suppress the development of further drug resistance.