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Item ASO Visual Abstract: Breast Cancer Screening, Diagnosis, and Surgery During the Pre- and Peri-pandemic—Experience of Patients in a Statewide Health Information Exchange(Springer, 2023) Milgrom, Zheng Z.; Milgrom, Daniel P.; Han, Yan; Hui, Siu L.; Haggstrom, David A.; Fisher, Carla S.; Mendonca, Eneida A.; Pediatrics, School of MedicineThe COVID-19 pandemic affected delivery of breast cancer care, including screening, diagnosis, and surgery. This study (https://doi.org/10.1245/s10434-023-13119-w) compared patient data from 1 year before the outbreak, during lockdown, and 1 year after lockdown to identify changes in patterns or timeliness of care.Item Breast Cancer Screening, Diagnosis, and Surgery during the Pre- and Peri-pandemic: Experience of Patients in a Statewide Health Information Exchange(Springer Nature, 2023) Milgrom, Zheng Z.; Milgrom, Daniel P.; Han, Yan; Hui, Siu L.; Haggstrom, David A.; Fisher, Carla S.; Mendonca, Eneida A.; Pediatrics, School of MedicineBackground: Measures taken to address the COVID-19 pandemic interrupted routine diagnosis and care for breast cancer. The aim of this study was to characterize the effects of the pandemic on breast cancer care in a statewide cohort. Patients and methods: Using data from a large health information exchange, we retrospectively analyzed the timing of breast cancer screening, and identified a cohort of newly diagnosed patients with any stage of breast cancer to further access the information available about their surgical treatments. We compared data for four subgroups: pre-lockdown (preLD) 25 March to 16 June 2019; lockdown (LD) 23 March to 3 May 2020; reopening (RO) 4 May to 14 June 2020; and post-lockdown (postLD) 22 March to 13 June 2021. Results: During LD and RO, screening mammograms in the cohort decreased by 96.3% and 36.2%, respectively. The overall breast cancer diagnosis and surgery volumes decreased up to 38.7%, and the median time to surgery was prolonged from 1.5 months to 2.4 for LD and 1.8 months for RO. Interestingly, higher mean DCIS diagnosis (5.0 per week vs. 3.1 per week, p < 0.05) and surgery volume (14.8 vs. 10.5, p < 0.05) were found for postLD compared with preLD, while median time to surgery was shorter (1.2 months vs. 1.5 months, p < 0.0001). However, the postLD average weekly screening and diagnostic mammogram did not fully recover to preLD levels (2055.3 vs. 2326.2, p < 0.05; 574.2 vs. 624.1, p < 0.05). Conclusions: Breast cancer diagnosis and treatment patterns were interrupted during the lockdown and still altered 1 year after. Screening in primary care should be expanded to mitigate possible longer-term effects of these interruptions.Item The CAM-ICU-7 Delirium Severity Scale: A Novel Delirium Severity Instrument for Use in the Intensive Care Unit(Wolters Kluwer, 2017-05) Khan, Babar A.; Perkins, Anthony J.; Gao, Sujuan; Hui, Siu L.; Campbell, Noll L.; Farber, Mark O.; Chlan, Linda L.; Boustani, Malaz A.; Medicine, School of MedicineOBJECTIVES: Delirium severity is independently associated with longer hospital stays, nursing home placement, and death in patients outside the ICU. Delirium severity in the ICU is not routinely measured because the available instruments are difficult to complete in critically ill patients. We designed our study to assess the reliability and validity of a new ICU delirium severity tool, the Confusion Assessment Method for the ICU-7 delirium severity scale. DESIGN: Observational cohort study. SETTING: Medical, surgical, and progressive ICUs of three academic hospitals. PATIENTS: Five hundred eighteen adult (≥ 18 yr) patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients received the Confusion Assessment Method for the ICU, Richmond Agitation-Sedation Scale, and Delirium Rating Scale-Revised-98 assessments. A 7-point scale (0-7) was derived from responses to the Confusion Assessment Method for the ICU and Richmond Agitation-Sedation Scale items. Confusion Assessment Method for the ICU-7 showed high internal consistency (Cronbach's α = 0.85) and good correlation with Delirium Rating Scale-Revised-98 scores (correlation coefficient = 0.64). Known-groups validity was supported by the separation of mechanically ventilated and nonventilated assessments. Median Confusion Assessment Method for the ICU-7 scores demonstrated good predictive validity with higher odds (odds ratio = 1.47; 95% CI = 1.30-1.66) of in-hospital mortality and lower odds (odds ratio = 0.8; 95% CI = 0.72-0.9) of being discharged home after adjusting for age, race, gender, severity of illness, and chronic comorbidities. Higher Confusion Assessment Method for the ICU-7 scores were also associated with increased length of ICU stay (p = 0.001). CONCLUSIONS: Our results suggest that Confusion Assessment Method for the ICU-7 is a valid and reliable delirium severity measure among ICU patients. Further research comparing it to other delirium severity measures, its use in delirium efficacy trials, and real-life implementation is needed to determine its role in research and clinical practice.Item Cardiovascular disease in thymic cancer patients(Frontiers Media, 2024-09-10) Khemka, Abhishek; Clasen, Suparna C.; Loehrer, Patrick J.; Roberts, Anna R.; Golzarri-Arroyo, Lilian; Badve, Sunil S.; Raman, Subha V.; Hui, Siu L.; Schleyer, Titus K. L.; Medicine, School of MedicineIntroduction: Cancer patients may have increased risk for adverse cardiac events, but our understanding of cardiovascular risk in thymic cancer patients is not clear. We sought to characterize baseline cardiometabolic risk factors before thymic cancer diagnosis and the potential association between cancer treatment and subsequent cardiac events. Methods: This was a retrospective cohort study evaluating patients with thymic cancer from 2003 to 2020 compared to age- and sex-matched controls without cancer. Baseline cardiovascular risk factors, cancer characteristics, and incidence of cardiac events were collected from the health information exchange. Multivariable regression was used to examine the impact of cardiovascular risk factors and cancer therapies. Results: We compared 296 patients with pathology-confirmed thymic cancer to 2,960 noncancer controls. Prior to cancer diagnosis, thymic cancer patients (TCPs) had lower prevalence of hypertension, dyslipidemia, and diabetes mellitus and similar rates of obesity, tobacco use, and pre-existing cardiovascular disease (CVD) compared to controls. After diagnosis, high-risk TCPs (>2 cardiovascular risk factors or pre-existing CVD) had higher risk for cardiac events (HR 3.73, 95% CI 2.88-4.83, p < 0.001). In the first 3 years after diagnosis, TCPs had higher incidence of cardiac events (HR 1.38, 95% CI 1.01-1.87, p = 0.042). High-risk TCPs who received radiotherapy or chemotherapy had higher risk of cardiac events (HR 4.99, 95% CI 2.30-10.81, p < 0.001; HR 6.24, 95% CI 2.84-13.72, p < 0.001). Discussion/conclusion: Compared to noncancer controls, TCPs experienced more cardiac events when adjusted for risk factors. Patients with multiple cardiovascular risk factors receiving radiotherapy or chemotherapy had higher incidence of cardiac events.Item Database queries for hospitalizations for acute congestive heart failure: flexible methods and validation based on set theory(Oxford University Press, 2014-03-01) Rosenman, Marc; He, Jinghua; Martin, Joel; Nutakki, Kavitha; Eckert, George; Lane, Kathleen; Gradus-Pizlo, Irmina; Hui, Siu L.; Department of Pediatrics, IU School of MedicineBackground and objective Electronic health records databases are increasingly used for identifying cohort populations, covariates, or outcomes, but discerning such clinical ‘phenotypes’ accurately is an ongoing challenge. We developed a flexible method using overlapping (Venn diagram) queries. Here we describe this approach to find patients hospitalized with acute congestive heart failure (CHF), a sampling strategy for one-by-one ‘gold standard’ chart review, and calculation of positive predictive value (PPV) and sensitivities, with SEs, across different definitions. Materials and methods We used retrospective queries of hospitalizations (2002–2011) in the Indiana Network for Patient Care with any CHF ICD-9 diagnoses, a primary diagnosis, an echocardiogram performed, a B-natriuretic peptide (BNP) drawn, or BNP >500 pg/mL. We used a hybrid between proportional sampling by Venn zone and over-sampling non-overlapping zones. The acute CHF (presence/absence) outcome was based on expert chart review using a priori criteria. Results Among 79 091 hospitalizations, we reviewed 908. A query for any ICD-9 code for CHF had PPV 42.8% (SE 1.5%) for acute CHF and sensitivity 94.3% (1.3%). Primary diagnosis of 428 and BNP >500 pg/mL had PPV 90.4% (SE 2.4%) and sensitivity 28.8% (1.1%). PPV was <10% when there was no echocardiogram, no BNP, and no primary diagnosis. ‘False positive’ hospitalizations were for other heart disease, lung disease, or other reasons. Conclusions This novel method successfully allowed flexible application and validation of queries for patients hospitalized with acute CHF.Item Design of the Association of Uterine Perforation and Expulsion of Intrauterine Device study: a multisite retrospective cohort study(Elsevier, 2021) Anthony, Mary S.; Reed, Susan D.; Armstrong, Mary Anne; Getahun, Darios; Gatz, Jennifer L.; Saltus, Catherine W.; Zhou, Xiaolei; Schoendorf, Juliane; Postlethwaite, Debbie A.; Raine-Bennett, Tina; Fassett, Michael J.; Peipert, Jeffrey F.; Ritchey, Mary E.; Ichikawa, Laura E.; Lynen, Richard; Alabaster, Amy L.; Merchant, Maqdooda; Chiu, Vicki Y.; Shi, Jiaxiao M.; Xie, Fagen; Hui, Siu L.; Wang, Jinyi; Hunter, Shannon; Bartsch, Jennifer; Frenz, Ann-Kathrin; Chillemi, Giulia; Im, Theresa M.; Takhar, Harpreet S.; Asiimwe, Alex; Obstetrics and Gynecology, School of MedicineBackground Intrauterine devices are effective and safe, long-acting reversible contraceptives, but the risk of uterine perforation occurs with an estimated incidence of 1 to 2 per 1000 insertions. The European Active Surveillance Study for Intrauterine Devices, a European prospective observational study that enrolled 61,448 participants (2006–2012), found that women breastfeeding at the time of device insertion or with the device inserted at ≤36 weeks after delivery had a higher risk of uterine perforation. The Association of Uterine Perforation and Expulsion of Intrauterine Device (APEX-IUD) study was a Food and Drug Administration–mandated study designed to reflect current United States clinical practice. The aims of the APEX-IUD study were to evaluate the risk of intrauterine device–related uterine perforation and device expulsion among women who were breastfeeding or within 12 months after delivery at insertion. Objective We aimed to describe the APEX-IUD study design, methodology, and analytical plan and present population characteristics, size of risk factor groups, and duration of follow-up. Study Design APEX-IUD study was a retrospective cohort study conducted in 4 organizations with access to electronic health records: Kaiser Permanente Northern California, Kaiser Permanente Southern California, Kaiser Permanente Washington, and Regenstrief Institute in Indiana. Variables were identified through structured data (eg, diagnostic, procedural, medication codes) and unstructured data (eg, clinical notes) via natural language processing. Outcomes include uterine perforation and device expulsion; potential risk factors were breastfeeding at insertion, postpartum timing of insertion, device type, and menorrhagia diagnosis in the year before insertion. Covariates include demographic characteristics, clinical characteristics, and procedure-related variables, such as difficult insertion. The first potential date of inclusion for eligible women varies by research site (from January 1, 2001 to January 1, 2010). Follow-up begins at insertion and ends at first occurrence of an outcome of interest, a censoring event (device removal or reinsertion, pregnancy, hysterectomy, sterilization, device expiration, death, disenrollment, last clinical encounter), or end of the study period (June 30, 2018). Comparisons of levels of exposure variables were made using Cox regression models with confounding adjusted by propensity score weighting using overlap weights. Results The study population includes 326,658 women with at least 1 device insertion during the study period (Kaiser Permanente Northern California, 161,442; Kaiser Permanente Southern California, 123,214; Kaiser Permanente Washington, 20,526; Regenstrief Institute, 21,476). The median duration of continuous enrollment was 90 (site medians 74–177) months. The mean age was 32 years, and the population was racially and ethnically diverse across the 4 sites. The mean body mass index was 28.5 kg/m2, and of the women included in the study, 10.0% had menorrhagia ≤12 months before insertion, 5.3% had uterine fibroids, and 10% were recent smokers; furthermore, among these women, 79.4% had levonorgestrel-releasing devices, and 19.5% had copper devices. Across sites, 97,824 women had an intrauterine device insertion at ≤52 weeks after delivery, of which 94,817 women (97%) had breastfeeding status at insertion determined; in addition, 228,834 women had intrauterine device insertion at >52 weeks after delivery or no evidence of a delivery in their health record. Conclusion Combining retrospective data from multiple sites allowed for a large and diverse study population. Collaboration with clinicians in the study design and validation of outcomes ensured that the APEX-IUD study results reflect current United States clinical practice. Results from this study will provide valuable information based on real-world evidence about risk factors for intrauterine devices perforation and expulsion for clinicians.Item Development, validation, and proof-of-concept implementation of a two-year risk prediction model for undiagnosed atrial fibrillation using common electronic health data (UNAFIED)(BMC, 2021-04-03) Grout, Randall W.; Hui, Siu L.; Imler, Timothy D.; El‑Azab, Sarah; Sands, George H.; Ateya, Mohammad; Pike, Francis; Pediatrics, School of MedicineBackground: Many patients with atrial fibrillation (AF) remain undiagnosed despite availability of interventions to reduce stroke risk. Predictive models to date are limited by data requirements and theoretical usage. We aimed to develop a model for predicting the 2-year probability of AF diagnosis and implement it as proof-of-concept (POC) in a production electronic health record (EHR). Methods: We used a nested case-control design using data from the Indiana Network for Patient Care. The development cohort came from 2016 to 2017 (outcome period) and 2014 to 2015 (baseline). A separate validation cohort used outcome and baseline periods shifted 2 years before respective development cohort times. Machine learning approaches were used to build predictive model. Patients ≥ 18 years, later restricted to age ≥ 40 years, with at least two encounters and no AF during baseline, were included. In the 6-week EHR prospective pilot, the model was silently implemented in the production system at a large safety-net urban hospital. Three new and two previous logistic regression models were evaluated using receiver-operating characteristics. Number, characteristics, and CHA2DS2-VASc scores of patients identified by the model in the pilot are presented. Results: After restricting age to ≥ 40 years, 31,474 AF cases (mean age, 71.5 years; female 49%) and 22,078 controls (mean age, 59.5 years; female 61%) comprised the development cohort. A 10-variable model using age, acute heart disease, albumin, body mass index, chronic obstructive pulmonary disease, gender, heart failure, insurance, kidney disease, and shock yielded the best performance (C-statistic, 0.80 [95% CI 0.79-0.80]). The model performed well in the validation cohort (C-statistic, 0.81 [95% CI 0.8-0.81]). In the EHR pilot, 7916/22,272 (35.5%; mean age, 66 years; female 50%) were identified as higher risk for AF; 5582 (70%) had CHA2DS2-VASc score ≥ 2. Conclusions: Using variables commonly available in the EHR, we created a predictive model to identify 2-year risk of developing AF in those previously without diagnosed AF. Successful POC implementation of the model in an EHR provided a practical strategy to identify patients who may benefit from interventions to reduce their stroke risk.Item Effectiveness of implementing a wake up and breathe program on sedation and delirium in the ICU(Ovid Technologies (Wolters Kluwer) - Lippincott Williams & Wilkins, 2014-12) Khan, Babar A.; Fadel, William F.; Tricker, Jason L.; Carlos, W. Graham; Farber, Mark O.; Hui, Siu L.; Campbell, Noll L.; Ely, E. Wesley; Boustani, Malaz A.; Department of Medicine, IU School of MedicineOBJECTIVES: Mechanically ventilated critically ill patients receive significant amounts of sedatives and analgesics that increase their risk of developing coma and delirium. We evaluated the impact of a "Wake-up and Breathe Protocol" at our local ICU on sedation and delirium. DESIGN: A pre/post implementation study design. SETTING: A 22-bed mixed surgical and medical ICU. PATIENTS: Seven hundred two consecutive mechanically ventilated ICU patients from June 2010 to January 2013. INTERVENTIONS: Implementation of daily paired spontaneous awakening trials (daily sedation vacation plus spontaneous breathing trials) as a quality improvement project. MEASUREMENTS AND MAIN RESULTS: After implementation of our program, there was an increase in the mean Richmond Agitation Sedation Scale scores on weekdays of 0.88 (p < 0.0001) and an increase in the mean Richmond Agitation Sedation Scale scores on weekends of 1.21 (p < 0.0001). After adjusting for age, race, gender, severity of illness, primary diagnosis, and ICU, the incidence and prevalence of delirium did not change post implementation of the protocol (incidence: 23% pre vs 19.6% post; p = 0.40; prevalence: 66.7% pre vs 55.3% post; p = 0.06). The combined prevalence of delirium/coma decreased from 90.8% pre protocol implementation to 85% postimplementation (odds ratio, 0.505; 95% CI, 0.299-0.853; p = 0.01). CONCLUSIONS: Implementing a "Wake Up and Breathe Program" resulted in reduced sedation among critically ill mechanically ventilated patients but did not change the incidence or prevalence of delirium.Item Incorporating conditional dependence in latent class models for probabilistic record linkage: Does it matter?(ims, 2019) Xu, Huiping; Li, Xiaochun; Shen, Changyu; Hui, Siu L.; Grannis, Shaun; Family Medicine, School of MedicineThe conditional independence assumption of the Felligi and Sunter (FS) model in probabilistic record linkage is often violated when matching real-world data. Ignoring conditional dependence has been shown to seriously bias parameter estimates. However, in record linkage, the ultimate goal is to inform the match status of record pairs and therefore, record linkage algorithms should be evaluated in terms of matching accuracy. In the literature, more flexible models have been proposed to relax the conditional independence assumption, but few studies have assessed whether such accommodations improve matching accuracy. In this paper, we show that incorporating the conditional dependence appropriately yields comparable or improved matching accuracy than the FS model using three real-world data linkage examples. Through a simulation study, we further investigate when conditional dependence models provide improved matching accuracy. Our study shows that the FS model is generally robust to the conditional independence assumption and provides comparable matching accuracy as the more complex conditional dependence models. However, when the match prevalence approaches 0% or 100% and conditional dependence exists in the dominating class, it is necessary to address conditional dependence as the FS model produces suboptimal matching accuracy. The need to address conditional dependence becomes less important when highly discriminating fields are used. Our simulation study also shows that conditional dependence models with misspecified dependence structure could produce less accurate record matching than the FS model and therefore we caution against the blind use of conditional dependence models.Item Initial uptake, time to treatment, and real-world effectiveness of all-oral direct-acting antivirals for hepatitis C virus infection in the United States: A retrospective cohort analysis(PLOS, 2019-08-22) Kwo, Paul Y.; Puenpatom, Amy; Zhang, Zuoyi; Hui, Siu L.; Kelley, Andrea A.; Muschi, David; Biostatistics, School of Public HealthBACKGROUND: Data on initiation and utilization of direct-acting antiviral therapies for hepatitis C virus infection in the United States are limited. This study evaluated treatment initiation, time to treatment, and real-world effectiveness of direct-acting antiviral therapy in individuals with hepatitis C virus infection treated during the first 2 years of availability of all-oral direct-acting antiviral therapies. METHODS: A retrospective cohort analysis was undertaken using electronic medical records and chart review abstraction of hepatitis C virus-infected individuals aged >18 years diagnosed with chronic hepatitis C virus infection between January 1, 2014, and December 31, 2015 from the Indiana University Health database. RESULTS: Eight hundred thirty people initiated direct-acting antiviral therapy during the 2-year observation window. The estimated incidence of treatment initiation was 8.8%±0.34% at the end of year 1 and 15.0%±0.5% at the end of year 2. Median time to initiating therapy was 300 days. Using a Cox regression analysis, positive predictors of treatment initiation included age (hazard ratio, 1.008), prior hepatitis C virus treatment (1.74), cirrhosis (2.64), and history of liver transplant (1.5). History of drug abuse (0.43), high baseline alanine aminotransferase levels (0.79), hepatitis B virus infection (0.41), and self-pay (0.39) were negatively associated with treatment initiation. In the evaluable population (n = 423), 83.9% (95% confidence interval, 80.1-87.3%) of people achieved sustained virologic response. CONCLUSION: In the early years of the direct-acting antiviral era, <10% of people diagnosed with chronic hepatitis C virus infection received direct-acting antiviral treatment; median time to treatment initiation was 300 days. Future analyses should evaluate time to treatment initiation among those with less advanced fibrosis.