Inequalities in access to prenatal care during the COVID-19 pandemic: Analysis of a population-based cohort.

BACKGROUND: Before the COVID-19 pandemic, access to prenatal care was lower among some socio-demographic groups. This pandemic caused disruptions to routine preventative care, which could have increased inequalities. OBJECTIVES: To investigate if the COVID-19 pandemic increased inequalities in access to prenatal care among those who are younger, live in rural areas, have a lower socio-economic situation (SES) and are recent immigrants. METHODS: We used linked administrative datasets from ICES to identify a population-based cohort of 455,245 deliveries in Ontario from January 2018 to December 2021. Our outcomes were first-trimester prenatal visits, first-trimester ultrasound and adequacy of prenatal care. We used joinpoint analysis to examine outcome time trends and identify trend change points. We stratified analyses by age, rural residence, SES and recent immigration, and examined risk differences (RD) with 95% confidence intervals (CI) between groups at the beginning and end of the study period. RESULTS: For all outcomes, we noted disruptions to care beginning in March or April 2020 and returning to previous trends by November 2020. Inequalities were stable across groups, except recent immigrants. In July 2017, 65.0% and 69.8% of recent immigrants and non-immigrants, respectively, received ultrasounds in the first trimester (RD -4.8%, 95% CI -8.0, -1.5). By October 2020, this had increased to 75.4%, with no difference with non-immigrants (RD 0.4%, 95% CI -2.4, 3.2). Adequacy of prenatal care showed more intensive care as of November 2020, reflecting a higher number of visits. CONCLUSIONS: We found no evidence that inequalities between socio-economic groups that existed prior to the pandemic worsened after March 2020. The pandemic may be associated with increased access to care for recent immigrants. The introduction of virtual visits may have resulted in a higher number of prenatal care visits.

Average Estimates in Line Graphs Are Biased Toward Areas of Higher Variability.

We investigate variability overweighting, a previously undocumented bias in line graphs, where estimates of average value are biased toward areas of higher variability in that line. We found this effect across two preregistered experiments with 140 and 420 participants. These experiments also show that the bias is reduced when using a dot encoding of the same series. We can model the bias with the average of the data series and the average of the points drawn along the line. This bias might arise because higher variability leads to stronger weighting in the average calculation, either due to the longer line segments (even though those segments contain the same number of data values) or line segments with higher variability being otherwise more visually salient. Understanding and predicting this bias is important for visualization design guidelines, recommendation systems, and tool builders, as the bias can adversely affect estimates of averages and trends.

Amphetamine-Related Emergency Department Visits in Ontario, Canada, 2003-2020.

OBJECTIVES: Despite unregulated amphetamine use increasing, there are limited data on related emergency department (ED) visits in Canada. Our primary objective was to examine trends in amphetamine-related ED visits over time in Ontario, including by age and sex. Secondary objectives were to examine whether patient characteristics were associated with ED revisit within 6 months. METHODS: Using administrative claims and census data, we calculated annual patient- and encounter-based rates of amphetamine-related ED visits from 2003 to 2020 among individuals 18+ years of age. We also performed a retrospective cohort study of individuals with amphetamine-related ED visits between 2019 and 2020 to determine whether select factors were associated with ED revisit within 6 months. Multivariable logistic regression modelling was used to measure associations. RESULTS: The population-based rate of amphetamine-related ED visits increased nearly 15-fold between 2003 (1.9/100,000 Ontarians) and 2020 (27.9/100,000 Ontarians). Seventy-five percent of individuals returned to the ED for any reason within 6 months. Psychosis and use of other substances were both independently associated with ED revisit for any reason within 6 months (psychosis: AOR = 1.54, 95% CI = 1.30-1.83; other substances: AOR = 1.84, 95% CI = 1.57-2.15), whereas having a primary care physician was negatively associated with ED revisit (AOR = 0.77, 95% CI = 0.60-0.98). CONCLUSIONS: Increasing rates of amphetamine-related ED visits in Ontario are cause for concern. Diagnoses of psychosis and the use of other substances may serve to identify individuals who are most likely to benefit from both primary and substance-specific care.

Direct Oral Anticoagulation Versus Warfarin in Patients with Atrial Fibrillation and Bioprosthetic Heart Valves: a Retrospective, Real-World Cohort Study.

OBJECTIVE: In this retrospective cohort study of consecutive patients with atrial fibrillation and surgical or transcatheter bioprosthetic valve, we compared the efficacy and safety of direct oral anticoagulants with warfarin. METHODS: Using linked health administrative databases housed at the Institute for Clinical Evaluative Sciences, we identified consecutive patients in Ontario (Canada) 65 years of age or older with AF who underwent bioprosthetic valve replacement between 1 April 2012 and 31 March 2017. We created a time-varying Cox model to examine the relationship between the type of anticoagulant and time to thrombotic or bleeding events after adjustment for baseline risk of thrombosis using the CHA2DS2-VASc score and risk of bleeding using the HAS-BLED scores. We conducted prespecified subgroup analyses according to whether valve implantation was surgical or transcatheter. RESULTS: We identified 2245 eligible patients. The mean age was 79 years, 41% were female, and 39% had transcatheter aortic valve replacement. Risk of death or thrombosis was not different between direct oral anticoagulants and warfarin after adjustment for CHA2DS2-VASc score (hazard ratio [HR] 1.02, 95% confidence interval [CI], 0.83-1.25). Risk of death or bleeding was not different between direct oral anticoagulants and warfarin after adjustment for HAS-BLED score (HR 0.89, 95% CI 0.75-1.07). Subgroup analyses of surgical or transcatheter valves were consistent with overall results. CONCLUSIONS: In a real-world population of patients with atrial fibrillation and bioprosthetic valve replacement, we found no difference between direct oral anticoagulants and warfarin with regard to the risk of thrombosis or bleeding.

An Agile Systems Modeling Framework for Bed Resource Planning During COVID-19 Pandemic in Singapore.

Background: The COVID-19 pandemic has had a major impact on health systems globally. The sufficiency of hospitals' bed resource is a cornerstone for access to care which can significantly impact the public health outcomes. Objective: We describe the development of a dynamic simulation framework to support agile resource planning during the COVID-19 pandemic in Singapore. Materials and Methods: The study data were derived from the Singapore General Hospital and public domain sources over the period from 1 January 2020 till 31 May 2020 covering the period when the initial outbreak and surge of COVID-19 cases in Singapore happened. The simulation models and its variants take into consideration the dynamic evolution of the pandemic and the rapidly evolving policies and processes in Singapore. Results: The models were calibrated against historical data for the Singapore COVID-19 situation. Several variants of the resource planning model were rapidly developed to adapt to the fast-changing COVID-19 situation in Singapore. Conclusion: The agility in adaptable models and robust collaborative management structure enabled the quick deployment of human and capital resources to sustain the high level of health services delivery during the COVID-19 surge.

Length of initial prescription at hospital discharge and long-term medication adherence for elderly, post-myocardial infarction patients: a population-based interrupted time series study.

BACKGROUND: Preliminary evidence suggests that providing longer duration prescriptions at discharge may improve long-term adherence to secondary preventative cardiac medications among post-myocardial infarction (MI) patients. We implemented and assessed the effects of two hospital-based interventions-(1) standardized prolonged discharge prescription forms (90-day supply with 3 repeats for recommended cardiac medications) plus education and (2) education only-on long-term cardiac medication adherence among elderly patients post-MI. METHODS: We conducted an interrupted time series study of all post-MI patients aged 65-104 years in Ontario, Canada, discharged from hospital between September 2015 and August 2018 with ≥ 1 dispensation(s) for a statin, beta blocker, angiotensin system inhibitor, and/or secondary antiplatelet within 7 days post-discharge. The standardized prolonged discharge prescription forms plus education and education-only interventions were implemented at 2 (1,414 patients) and 4 (926 patients) non-randomly selected hospitals in September 2017 for 12 months, with all other Ontario hospitals (n = 143; 18,556 patients) comprising an external control group. The primary outcome, long-term cardiac medication adherence, was defined at the patient-level as an average proportion of days covered (over 1-year post-discharge) ≥ 80% across cardiac medication classes dispensed at their index fill. Primary outcome data were aggregated within hospital groups (intervention 1, 2, or control) to monthly proportions and independently analyzed using segmented regression to evaluate intervention effects. A process evaluation was conducted to assess intervention fidelity. RESULTS: At 12 months post-implementation, there was no statistically significant effect on long-term cardiac medication adherence for either intervention-standardized prolonged discharge prescription forms plus education (5.4%; 95% CI - 6.4%, 17.2%) or education only (1.0%; 95% CI - 28.6%, 30.6%)-over and above the counterfactual trend; similarly, no change was observed in the control group (- 0.3%; 95% CI - 3.6%, 3.1%). During the intervention period, only 10.8% of patients in the intervention groups received ≥ 90 days, on average, for cardiac medications at their index fill. CONCLUSIONS: Recognizing intervention fidelity was low at the pharmacy level, and no statistically significant post-implementation differences in adherence were found, the trends in this study-coupled with other published retrospective analyses of administrative data-support further evaluation of this simple intervention to improve long-term adherence to cardiac medications. TRIAL REGISTRATION: ClinicalTrials.gov : NCT03257579 , registered June 16, 2017 Protocol available at: https://pubmed.ncbi.nlm.nih.gov/33146624/ .

Specialty Psychiatric Services in US Emergency Departments and General Hospitals: Results From a Nationwide Survey.

OBJECTIVE: To explore the handling of psychiatric patients in medical hospitals and emergency departments (EDs) as well as hospital characteristics associated with the availability of psychiatric services in these settings. METHODS: From October 1, 2017, to April 1, 2018, a telephone survey regarding the presence and nature of psychiatric services was attempted among all US registered Medicare hospitals. RESULTS: Of the included 4812 US hospitals, 2394 (50%) were surveyed. Of these hospitals, 1108 (46%) have some psychiatric services available, either in medical EDs or through psychiatric consultation on general medical inpatient wards. If medical ED patients with active psychiatric issues need admission, 59% of hospitals transfer the patient to a different hospital and 28% admit the patient to a medical ward. Exploration by logistic regression analysis of the association of selected variables and available psychiatric expertise suggested that larger hospitals, nonprofit services, or hospitals in urban settings were more likely to have psychiatrists on staff or available for consultation. CONCLUSION: Despite the growing number of psychiatric patients seeking help in medical EDs and general hospitals, more than 50% of the EDs and general hospitals lack psychiatric services. These results suggest that accessibility to psychiatric care in medical settings requires improvement.

Resuming elective surgery after COVID-19: A simulation modelling framework for guiding the phased opening of operating rooms.

OBJECTIVE: To develop a 2-stage discrete events simulation (DES) based framework for the evaluation of elective surgery cancellation strategies and resumption scenarios across multiple operational outcomes. MATERIALS AND METHODS: Study data was derived from the data warehouse and domain knowledge on the operational process of the largest tertiary hospital in Singapore. 34,025 unique cases over 43 operating rooms (ORs) and 18 surgical disciplines performed from 1 January 2019 to 31 May 2020 were extracted for the study. A clustering approach was used in stage 1 of the modelling framework to develop the groups of surgeries that followed distinctive postponement patterns. These clusters were then used as inputs for stage 2 where the DES model was used to evaluate alternative phased resumption strategies considering the outcomes of OR utilization, waiting times to surgeries and the time to clear the backlogs. RESULTS: The tool enabled us to understand the elective postponement patterns during the COVID-19 partial lockdown period, and evaluate the best phased resumption strategy. Differences in the performance measures were evaluated based on 95% confidence intervals. The results indicate that two of the gradual phased resumption strategies provided lower peak OR and bed utilizations but required a longer time to return to BAU levels. Minimum peak bed demands could also be reduced by approximately 14 beds daily with the gradual resumption strategy, whilst the maximum peak bed demands by approximately 8.2 beds. Peak OR utilization could be reduced to 92% for gradual resumption as compared to a minimum peak of 94.2% with the full resumption strategy. CONCLUSIONS: The 2-stage modelling framework coupled with a user-friendly visualization interface were key enablers for understanding the elective surgery postponement patterns during a partial lockdown phase. The DES model enabled the identification and evaluation of optimal phased resumption policies across multiple important operational outcome measures. LAY ABSTRACT: During the height of the COVID-19 pandemic, most healthcare systems suspended their non-urgent elective surgery services. This strategy was undertaken as a means to expand surge capacity, through the preservation of structural resources (such as operating theaters, ICU beds, and ventilators), consumables (such as personal protective equipment and medications), and critical healthcare manpower. As a result, some patients had less-essential surgeries postponed due to the pandemic. As the first wave of the pandemic waned, there was an urgent need to quickly develop optimal strategies for the resumption of these surgeries. We developed a 2-stage discrete events simulation (DES) framework based on 34,025 unique cases over 43 operating rooms (ORs) and 18 surgical disciplines performed from 1 January 2019 to 31 May 2020 captured in the Singapore General Hospital (SGH) enterprise data warehouse. The outcomes evaluated were OR utilization, waiting times to surgeries and time to clear the backlogs. A user-friendly visualization interface was developed to enable decision makers to determine the most promising surgery resumption strategy across these outcomes. Hospitals globally can make use of the modelling framework to adapt to their own surgical systems to evaluate strategies for postponement and resumption of elective surgeries.

The impact of multimorbidity level and functional limitations on the accuracy of using self-reported survey data compared to administrative data to measure general practitioner and specialist visits in community-living adults.

BACKGROUND: Researchers often use survey data to study the effect of health and social variables on physician use, but how self-reported physician use compares to administrative data, the gold standard, in particular within the context of multimorbidity and functional limitations remains unclear. We examine whether multimorbidity and functional limitations are related to agreement between self-reported and administrative data for physician use. METHODS: Cross-sectional data from 52,854 Ontario participants of the Canadian Community Health Survey linked to administrative data were used to assess agreement on physician use. The number of general practitioner (GP) and specialist visits in the previous year was assessed using both data sources; multimorbidity and functional limitation were from self-report. RESULTS: Fewer participants self-reported GP visits (84.8%) compared to administrative data (89.1%), but more self-reported specialist visits (69.2% vs. 64.9%). Sensitivity was higher for GP visits (≥90% for all multimorbidity levels) compared to specialist visits (approximately 75% for 0 to 90% for 4+ chronic conditions). Specificity started higher for GP than specialist visits but decreased more swiftly with multimorbidity level; in both cases, specificity levels fell below 50%. Functional limitations, age and sex did not impact the patterns of sensitivity and specificity seen across level of multimorbidity. CONCLUSIONS: Countries around the world collect health surveys to inform health policy and planning, but the extent to which these are linked with administrative, or similar, data are limited. Our study illustrates the potential for misclassification of physician use in self-report data and the need for sensitivity analyses or other corrections.

Comparison of 4-Year Health Care Expenditures Associated With Roux-en-Y Gastric Bypass vs Sleeve Gastrectomy.

Importance: Data on the long-term health care expenditures associated with bariatric surgery consisting of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy are lacking. Objective: To compare 4-year health care expenditures after RYGB vs sleeve gastrectomy, identify factors independently associated with 4-year health care expenditures, and compare the procedures in terms of subsequent hospitalizations, bariatric procedures, and all-cause mortality. Design, Setting, and Participants: In this propensity score-matched cohort study, all residents of Ontario, Canada, who underwent publicly funded surgery with RYGB (n = 6301) or sleeve gastrectomy (n = 926) from March 1, 2010, to March 31, 2015, and consented to participate in the Ontario Bariatric Registry were eligible for the study. Follow-up was completed on March 31, 2019, and data were analyzed from May 5, 2020, to May 20, 2021. Interventions: RYGB and sleeve gastrectomy. Main Outcomes and Measures: Publicly funded health care expenditures, subsequent hospitalizations, bariatric procedures, and mortality during the 4 years after RYGB or sleeve gastrectomy. Results: The 1:1 matched study cohorts consisted of 1624 patients (812 per cohort) with a mean (SD) age of 48.0 (10.6) years, and 1242 women (76.5%). The mean body mass index (calculated as weight in kilograms divided by height in square meters) was 51.9 (8.3) for the RYGB cohort and 51.9 (8.9) for the sleeve gastrectomy cohort. The 4-year cumulative costs were not statistically significantly different between RYGB and sleeve gastrectomy (mean [SD], $33 682 [$31 169] vs $33 948 [$32 633], respectively; P = .86). Having a history of coronary artery disease was associated with a 35% increase in overall health care expenditures; chronic kidney disease, a 54% increase; and mental health admissions, a 67% increase. There were no statistically significant differences in all-cause mortality between RYGB and sleeve gastrectomy (1.5% vs 2.2%, respectively; P = .26) or the total number of hospitalizations (754 vs 669, respectively; P = .11) during the 4-year follow-up period. However, nonelective hospitalizations occurred more frequently with RYGB vs sleeve gastrectomy (472 vs 339, respectively; P = .002). Roux-en-Y gastric bypass was associated with relatively fewer subsequent bariatric procedures during the 4-year follow-up period (9 vs 40, respectively; P < .001). Conclusions and Relevance: In this Canadian population-based study, key results indicated that 4-year health care expenditures, all-cause mortality, and number of hospital admissions associated with RYGB did not significantly differ from those for sleeve gastrectomy. The rate of subsequent bariatric surgery was lower with RYGB. This study identified important patient-level drivers of health care expenditures that need to be further investigated.

The impact of routine HIV drug resistance testing in Ontario: A controlled interrupted time series study.

BACKGROUND: Knowledge of HIV drug resistance informs the choice of regimens and ensures that the most efficacious options are selected. In January 2014, a policy change to routine resistance testing was implemented in Ontario, Canada. The objective of this study was to investigate the policy change impact of routine resistance testing in people with HIV in Ontario, Canada since January 2014. METHODS: We used data on people with HIV living in Ontario from administrative databases of the Institute for Clinical Evaluative Sciences (ICES) and Public Health Ontario (PHO), and ran ordinary least squares (OLS) models of interrupted time series to measure the levels and trends of 2-year mortality, 2-year hospitalizations and 2-year emergency department visits before (2005-2013) and after the policy change (2014-2017). Outcomes were collected in biannual periods, generating 18 periods before the intervention and 8 periods after. We included a control series of people who did not receive a resistance test within 3 months of HIV diagnosis. RESULTS: Data included 12,996 people with HIV, of which 8881 (68.3%) were diagnosed between 2005 and 2013, and 4115 (31.7%) were diagnosed between 2014 and 2017. Policy change to routine resistance testing within 3 months of HIV diagnosis led to a decreasing trend in 2-year mortality of 0.8% every six months compared to the control group. No significant differences in hospitalizations or emergency department visits were noted. INTERPRETATION: The policy of routine resistance testing within three months of diagnosis is beneficial at the population level.

Effect of socio-demographic and health factors on the association between multimorbidity and acute care service use: population-based survey linked to health administrative data.

BACKGROUND: This study explores how socio-demographic and health factors shape the relationship between multimorbidity and one-year acute care service use (i.e., hospital, emergency department visits) in older adults in Ontario, Canada. METHODS: We linked multiple cycles (2005-2006, 2007-2008, 2009-2010, 2011-2012) of the Canadian Community Health Survey (CCHS) to health administrative data to create a cohort of adults aged 65 and older. Administrative data were used to estimate one-year service use and to identify 12 chronic conditions used to measure multimorbidity. We examined the relationship between multimorbidity and service use stratified by a range of socio-demographic and health variables available from the CCHS. Logistic and Poisson regressions were used to explore the association between multimorbidity and service use and the role of socio-demographic factors in this relationship. RESULTS: Of the 28,361 members of the study sample, 60% were between the ages of 65 and 74 years, 57% were female, 72% were non-immigrant, and over 75% lived in an urban area. Emergency department visits and hospitalizations consistently increased with the level of multimorbidity. This study did not find strong evidence of moderator or interaction effects across a range of socio-demographic factors. Stratified analyses revealed further patterns, with many being similar for both services - e.g., the odds ratios were higher at all levels of multimorbidity for men, older age groups, and those with lower household income. Rurality and immigrant status influenced emergency department use (higher in rural residents and non-immigrants) but not hospitalizations. Multimorbidity and the range of socio-demographic variables remained significant predictors of service use in the regressions. CONCLUSIONS: Strong evidence links multimorbidity with increased acute care service use. This study showed that a range of factors did not modify this relationship. Nevertheless, the factors were independently associated with acute care service use, pointing to modifiable risk factors that can be the focus of resource allocation and intervention design to reduce service use in those with multimorbidity. The study's results suggest that optimizing acute care service use in older adults requires attention to both multimorbidity and social determinants, with programs that are multifactorial and integrated across the health and social service sectors.

Impact of Delayed Recognition of Iatrogenic Ureteral Injury in a Retrospective Population-Based Study.

INTRODUCTION: Iatrogenic ureteral injuries (IUIs) are rare but can lead to significant consequences if unrecognized at the time of injury. We compare the impact of immediate vs delayed recognition of IUIs on clinical, cost and health care utilization outcomes. METHODS: We conducted a population-based retrospective cohort study on patients who had a diagnosis of an IUI between 2003 and 2018. The primary independent variable was the time of diagnosis of IUI. The primary clinical outcomes evaluated included renal impairment and a composite outcome: hydronephrosis or stricture. Secondary outcomes included total direct health care costs and health care utilization. RESULTS: We identified 1,193 patients who experienced an IUI, 25.2% of whom had a delay in recognition. Delayed recognition of IUI was associated with hydronephrosis or stricture within 1 year following treatment of IUI (OR 2.27, 95% CI 1.69-3.04, p <0.0001) and renal impairment within 2 years following treatment of IUI (OR 2.69, 95% CI 1.84-3.94, p <0.0001) compared to immediate diagnosis. Total health care costs (incident rate ratio [IRR] 2.06, 95% CI 1.89-2.24, p <0.0001), emergency department visits (IRR 2.07, 95% CI 1.77-2.43, p <0.0001), hospitalizations (IRR 1.62, 95% CI 1.48-1.78, p <0.0001) and outpatient urology visits (IRR 1.45, 95% CI 1.31-1.60, p <0.0001) were significantly higher in those with delayed recognition compared to immediate. Previous radiation was significantly associated with delayed recognition of IUI (OR 0.64, 95% CI 0.42-0.97, p=0.04). CONCLUSIONS: Delayed recognition of IUI is associated with significant clinical, cost and health care utilization consequences.

Prescription patterns of outpatients and the potential of multiplexed pharmacogenomic testing.

BACKGROUND: Pre-emptive pharmacogenomic (PGx) testing is potentially an efficient approach to improve drug safety and efficacy but the target population to test is unclear. OBJECTIVES: We aim to describe the prescription pattern of PGx drugs among adult medical outpatients. METHODS: We estimated the 5-year cumulative incidence (CI) for receiving three groups of PGx drugs using competing risks analysis: (i) all PGx drugs, (ii) PGx drugs with guidelines and (iii) PGx drugs with serious clinical effects. Comparisons of CIs were also done by patient characteristics using Gray's test. RESULTS: The 5-year CIs of receiving any new PGx drug, PGx drug with guidelines and serious clinical effects were 42.6%, 37.3% and 13.7%, respectively. The 5-year CI of receiving any new PGx drug was higher for patients >40 years old (43.6% vs ≤40 years old 36.0%, P < 2.2 × 10-22 ), Malays and Indians (50.3% and 49.8% vs Chinese 31.1%, P < 2.2 × 10-22 ), those who attended one of the following four specialties at the index visit compared to other specialties (infectious diseases [46.2% vs 42.6%, P = 2.9 × 10-4 ], psychiatry [48.3% vs 42.3%, P = 7.4 × 10-13 ], renal [49.8% vs 40.9%, P < 2.2 × 10-22 ], and rheumatology and immunology [54.8% vs 41.7%, P < 2.2 × 10-22 ]) and those prescribed ≥5 drugs at index visit (51.7% vs 0-4 drugs 41.7%, P < 2.2 × 10-22 ). CONCLUSIONS: Medical outpatients have a substantial probability of benefiting from pre-emptive PGx testing and this is higher in certain subgroups of patients.

Defining Patient Engagement in Research: Results of a Systematic Review and Analysis: Report of the ISPOR Patient-Centered Special Interest Group.

OBJECTIVES: Lack of clarity on the definition of "patient engagement" has been highlighted as a barrier to fully implementing patient engagement in research. This study identified themes within existing definitions related to patient engagement and proposes a consensus definition of "patient engagement in research." METHODS: A systematic review was conducted to identify definitions of patient engagement and related terms in published literature (2006-2018). Definitions were extracted and qualitatively analyzed to identify themes and characteristics. A multistakeholder approach, including academia, industry, and patient representation, was taken at all stages. A proposed definition is offered based on a synthesis of the findings. RESULTS: Of 1821 abstracts identified and screened for eligibility, 317 were selected for full-text review. Of these, 169 articles met inclusion criteria, from which 244 distinct definitions were extracted for analysis. The most frequently defined terms were: "patient-centered" (30.5%), "patient engagement" (15.5%), and "patient participation" (13.4%). The majority of definitions were specific to the healthcare delivery setting (70.5%); 11.9% were specific to research. Among the definitions of "patient engagement," the most common themes were "active process," "patient involvement," and "patient as participant." In the research setting, the top themes were "patient as partner," "patient involvement," and "active process"; these did not appear in the top 3 themes of nonresearch definitions. CONCLUSION: Distinct themes are associated with the term "patient engagement" and with engagement in the "research" setting. Based on an analysis of existing literature and review by patient, industry, and academic stakeholders, we propose a scalable consensus definition of "patient engagement in research."

Validation of the kidney failure risk equation for end-stage kidney disease in Southeast Asia.

BACKGROUND: Patients with chronic kidney disease (CKD) are at high risk of end-stage kidney disease (ESKD). The Kidney Failure Risk Equation (KFRE), which predicts ESKD risk among patients with CKD, has not been validated in primary care clinics in Southeast Asia (SEA). Therefore, we aimed to (1) evaluate the performance of existing KFRE equations, (2) recalibrate KFRE for better predictive precision, and (3) identify optimally feasible KFRE thresholds for nephrologist referral and dialysis planning in SEA. METHODS: All patients with CKD visiting nine primary care clinics from 2010 to 2013 in Singapore were included and applied 4-variable KFRE equations incorporating age, sex, estimated glomerular filtration rate (eGFR), and albumin-to-creatinine ratio (ACR). ESKD onset within two and five years were acquired via linkage to the Singapore Renal Registry. A weighted Brier score (the squared difference between observed vs predicted ESKD risks), bias (the median difference between observed vs predicted ESKD risks) and precision (the interquartile range of the bias) were used to select the best-calibrated KFRE equation. RESULTS: The recalibrated KFRE (named Recalibrated Pooled KFRE SEA) performed better than existing and other recalibrated KFRE equations in terms of having a smaller Brier score (square root: 2.8% vs. 4.0-9.3% at 5 years; 2.0% vs. 6.1-9.1% at 2 years), less bias (2.5% vs. 3.3-5.2% at 5 years; 1.8% vs. 3.2-3.6% at 2 years), and improved precision (0.5% vs. 1.7-5.2% at 5 years; 0.5% vs. 3.8-4.2% at 2 years). Area under ROC curve for the Recalibrated Pooled KFRE SEA equations were 0.94 (95% confidence interval [CI]: 0.93 to 0.95) at 5 years and 0.96 (95% CI: 0.95 to 0.97) at 2 years. The optimally feasible KFRE thresholds were > 10-16% for 5-year nephrologist referral and > 45% for 2-year dialysis planning. Using the Recalibrated Pooled KFRE SEA, an estimated 82 and 89% ESKD events were included among 10% of subjects at highest estimated risk of ESKD at 5-year and 2-year, respectively. CONCLUSIONS: The Recalibrated Pooled KFRE SEA performs better than existing KFREs and warrants implementation in primary care settings in SEA.

BPG: Seamless, automated and interactive visualization of scientific data.

BACKGROUND: We introduce BPG, a framework for generating publication-quality, highly-customizable plots in the R statistical environment. RESULTS: This open-source package includes multiple methods of displaying high-dimensional datasets and facilitates generation of complex multi-panel figures, making it suitable for complex datasets. A web-based interactive tool allows online figure customization, from which R code can be downloaded for integration with computational pipelines. CONCLUSION: BPG provides a new approach for linking interactive and scripted data visualization and is available at http://labs.oicr.on.ca/boutros-lab/software/bpg or via CRAN at https://cran.r-project.org/web/packages/BoutrosLab.plotting.general.

Machine Learning for Integrating Data in Biology and Medicine: Principles, Practice, and Opportunities.

New technologies have enabled the investigation of biology and human health at an unprecedented scale and in multiple dimensions. These dimensions include myriad properties describing genome, epigenome, transcriptome, microbiome, phenotype, and lifestyle. No single data type, however, can capture the complexity of all the factors relevant to understanding a phenomenon such as a disease. Integrative methods that combine data from multiple technologies have thus emerged as critical statistical and computational approaches. The key challenge in developing such approaches is the identification of effective models to provide a comprehensive and relevant systems view. An ideal method can answer a biological or medical question, identifying important features and predicting outcomes, by harnessing heterogeneous data across several dimensions of biological variation. In this Review, we describe the principles of data integration and discuss current methods and available implementations. We provide examples of successful data integration in biology and medicine. Finally, we discuss current challenges in biomedical integrative methods and our perspective on the future development of the field.

Pathway-based subnetworks enable cross-disease biomarker discovery.

Biomarkers lie at the heart of precision medicine. Surprisingly, while rapid genomic profiling is becoming ubiquitous, the development of biomarkers usually involves the application of bespoke techniques that cannot be directly applied to other datasets. There is an urgent need for a systematic methodology to create biologically-interpretable molecular models that robustly predict key phenotypes. Here we present SIMMS (Subnetwork Integration for Multi-Modal Signatures): an algorithm that fragments pathways into functional modules and uses these to predict phenotypes. We apply SIMMS to multiple data types across five diseases, and in each it reproducibly identifies known and novel subtypes, and makes superior predictions to the best bespoke approaches. To demonstrate its ability on a new dataset, we profile 33 genes/nodes of the PI3K pathway in 1734 FFPE breast tumors and create a four-subnetwork prediction model. This model out-performs a clinically-validated molecular test in an independent cohort of 1742 patients. SIMMS is generic and enables systematic data integration for robust biomarker discovery.