Cancer incidence in immunocompromised patients: a single-center cohort study.

BACKGROUND: Diminished immune defense plays an important role in cancer development. Cancer risk in immunocompromised patients may differ. Identifying individuals with elevated cancer risk can inform strategies for routine cancer screening. This study aimed to understand and compare cancer incidence and risk in three patient groups: recipients of solid organ transplant (SOT) or hematopoietic stem cell transplant (HSCT); diagnosis of primary or secondary immunodeficiency disorder (PID/SID); and recipients of tumor necrosis factor inhibitor (TNF-i) therapy. METHODS: This retrospective cohort study used the University of Utah Health System database and Huntsman Cancer Institute tumor registry. Patients aged ≥18 years with SOT/HSCT, PID/SID or ≥ 3 months of TNF-i therapy were included. The date of transplant, diagnosis of PID/SID, or 1st TNF-i medication order date was defined as the index date. We calculated cumulative cancer incidence by Kaplan-Meier method. A Cox-proportional hazard regression model with a stepwise variable selection process was used to identify independent risk factors associated with the time to onset of a new primary cancer. RESULTS: In total, 13,887 patients were included which comprised of 2982 (21%) SOT/HSCT, 7542 (54%) PID/SID and 3363 (24%) patients receiving TNF-i. The mean (SD) age ranged from 46.8 (15) years - 50.4 (18.2) years. The proportion of white patients ranged from 72.3-84.8%. The estimated cumulative cancer incidence was 11.5% in the SOT/HSCT cohort, 14.3% in the PID/SID cohort, and 8.8% in the TNF-i cohort. The multivariable model adjusted for age, benign in-situ disease, Charlson Comorbidity Index, hypertension/cardiovascular disease/end stage renal disease, gender, race/ethnicity, and renal cyst as significant risk factors. The adjusted hazard ratios for cancer development in SOT/HSCT and PID/SID cohorts compared to the TNF-i cohort over the full follow-up period were 1.57 (95% CI: 1.16-2.13) and 2.14 (95% CI: 1.65-2.77), respectively. CONCLUSION: A significantly increased risk of cancer was observed in PID/SID patients and SOT/HSCT patients compared to TNF-i patients. Age ≥ 50 years, male gender, and clinical comorbidities were additional factors impacting cancer risk. PID/SID and SOT/HSCT patients may benefit from more intensive cancer screening.

BRCA testing and outcomes in women with breast cancer.

MAIN PURPOSE: Germline BRCA mutations (BRCAm) strongly influence the risk of developing breast cancer. This study aimed to understand the role of BRCAm testing in affected individuals and to assess its impact on the outcome of BRCAm carriers compared to non-carriers (BRCAwt) with breast cancer. RESEARCH QUESTION: The research question is "Does standard of care testing for BRCAm improve survival outcomes of breast cancer patients?" METHODS: In a single institution observational cohort study, demographic and clinical characteristics were compared between breast cancer patients with and without BRCAm. Frequency of BRCA testing was assessed. Survival outcomes were assessed by initial treatment setting stratified by BRCA status. RESULTS: Of 5712 identified women with breast cancer, 14.6% (n = 835) were tested for a BRCA mutation and had a documented result. The total number and proportion of women tested for a BRCAm increased between 2000 and 2014, resulting in an increased number of BRCAm carriers identified. However, the proportion of women who underwent testing and had a BRCAm decreased during the study period from 27.5% in 2000-2004 to 13.3% in 2010-2014. Disease-free survival was similar in the adjuvant and neoadjuvant treatment settings between BRCAm and BRCAwt patients. Progression-free survival on first line treatment and overall survival for patients with metastatic disease was also similar between BRCAm and BRCAwt patients. CONCLUSIONS: The proportion of women tested and the number of BRCAm identified increased during the study period despite a decreasing proportion of positive results among women tested.

Longitudinal changes in glycated haemoglobin following treatment intensification after inadequate response to two oral antidiabetic agents in patients with type 2 diabetes.

AIMS: To identify change in glycated haemoglobin (HbA1c) for 1 year after treatment intensification in patients with HbA1c >53 mmol/mol (7.0%) while on two classes of oral antidiabetic drugs (OADs). MATERIAL AND METHODS: A retrospective cohort study was conducted using a regional health plan claims database for the period January 1, 2010 to March 31, 2017. Patients with type 2 diabetes (T2DM) whose treatment was intensified with insulin, a glucagon-like peptide-1 receptor agonist or a third OAD within 365 days of having HbA1c ≥53 mmol/mol (7.0%) on two OADs were included. The HbA1c trajectory for 1 year after intensification was estimated using a mixed-effects regression model. RESULTS: The analysis included 1226 patients with a mean ± SD HbA1c at treatment intensification of 74.2 ± 18.7 mmol/mol (8.93 ± 1.7%). HbA1c was higher in the insulin group (74.2 mmol/mol) than in the non-insulin group (70.6 mmol/mol), as was the HbA1c decrease (P < 0.01) over the 1-year follow-up, particularly in patients with baseline HbA1c >9%. After intensification, insulin- and non-insulin-treated patients achieved an average change by month in HbA1c of -4.7 mmol/mol and -2.6 mmol/mol points, respectively. The analysis predicted HbA1c to be the lowest at 6 to 10 months post intensification, depending on intensification treatment and HbA1c at intensification; however, on average, HbA1c remained above 64.0 mmol/mol (8.0%). CONCLUSION: In patients with T2DM, intensification following an HbA1c value ≥53 mmol/mol (7.0%) while on two OADs was associated with a significant improvement in glycaemic control. Patients intensified with insulin had a higher baseline HbA1c but greater HbA1c reduction than those intensified with a non-insulin agent. However, HbA1c remained above 64 mmol/mol (8.0%) overall. Additional opportunity exists to further intensify therapy to improve glycaemic control.

Cost-effectiveness of early cancer surveillance for patients with Li-Fraumeni syndrome.

INTRODUCTION: Patients with germline TP53 pathogenic variants (Li-Fraumeni syndrome [LFS]) are at extremely high lifetime risk of developing cancer. Recent data suggest that tumor surveillance for patients with LFS may improve survival through early cancer detection. The objective of this study was to assess the cost-effectiveness of a cancer surveillance strategy for patients with LFS compared with those whose tumors present clinically. METHODS: A Markov decision analytic model was developed from a third-party payer perspective to estimate cost-effectiveness of routine cancer surveillance over a patient's lifetime. The model consisted of four possible health states: no cancer, cancer, post-cancer survivorship, and death. Model outcomes were costs (2015 United States Dollars [USD]), effectiveness (life years [LY] gained), and incremental cost-effectiveness ratio (ICER; change in cost/LY gained). One-way sensitivity analyses and probabilistic sensitivity analyses examined parameter uncertainty. RESULTS: The model showed a mean cost of $46 496 and $117 102 and yielded 23 and 27 LY for the nonsurveillance and surveillance strategies, respectively. The ICER for early cancer surveillance versus no surveillance was $17 125 per additional LY gained. At the commonly accepted willingness to pay threshold of $100 000/life-year gained, surveillance had a 98% probability of being the most cost-effective strategy for early cancer detection in this high-risk population. CONCLUSIONS: Presymptomatic cancer surveillance is cost-effective for patients with germline pathogenic variants in TP53. Lack of insurance coverage or reimbursement in this population may have significant consequences and leads to undetected cancers presenting in later stages of disease with worse clinical outcomes.

Impact of a genetic counseling requirement prior to genetic testing.

BACKGROUND: Genetic counseling by a Genetic Counselor (GC) is a requirement prior to genetic testing for cancer susceptibility genes (GC-mandate policy) for some insurers. This study evaluated the impact of this policy from the patient perspective. METHODS: Surveys were sent to individuals for whom their insurer ordered genetic testing for the cancer susceptibility genes BCRA1 and BRCA2 over a 1 year time period that spanned the introduction of a GC-mandate policy. Responses were assessed by time period (before/after policy introduction) and genetic test completion. RESULTS: The surveys were completed by 1247/4950 (25.7%) eligible individuals. After policy introduction, there was no change in the proportion of respondents who completed genetic testing (p = 0.13) or had a mutation (p = 0.55). Overall decisional conflict (uncertainty or feeling uninformed) around genetic testing did not change after policy introduction (p = 0.16), but was significantly higher among respondents who did not complete genetic testing (p < 0.01). Although a larger proportion of respondents saw a GC after policy introduction (p < 0.01), fewer did so to better understand their test results (p < 0.01). The proportion of respondents who did not see a GC due to insurance issues/requirements and time restraints was higher among those tested after policy introduction or who did not complete genetic testing (p < 0.01). In multivariate analysis, respondents with a household income of $25,000 or greater were 3-times more likely to complete testing. CONCLUSIONS: A GC-mandate policy did not improve decisional conflict or increase the number of deleterious mutations identified and low-income respondents were less likely to complete testing. On the contrary, insurance requirements and time constraints may be preventing individuals at risk from receiving appropriate testing.

Cost-Utility of a Prognostic Test Guiding Adjuvant Chemotherapy Decisions in Early-Stage Non-Small Cell Lung Cancer.

BACKGROUND: A prognostic test was developed to guide adjuvant chemotherapy (ACT) decisions in early-stage non-small cell lung cancer (NSCLC) adenocarcinomas. The objective of this study was to compare the cost-utility of the prognostic test to the current standard of care (SoC) in patients with early-stage NSCLC. MATERIALS AND METHODS: Lifetime costs (2014 U.S. dollars) and effectiveness (quality-adjusted life-years [QALYs]) of ACT treatment decisions were examined using a Markov microsimulation model from a U.S. third-party payer perspective. Cancer stage distribution and probability of receiving ACT with the SoC were based on data from an academic cancer center. The probability of receiving ACT with the prognostic test was estimated from a physician survey. Risk classification was based on the 5-year predicted NSCLC-related mortality. Treatment benefit with ACT was based on the prognostic score. Discounting at a 3% annual rate was applied to costs and QALYs. Deterministic one-way and probabilistic sensitivity analyses examined parameter uncertainty. RESULTS: Lifetime costs and effectiveness were $137,403 and 5.45 QALYs with the prognostic test and $127,359 and 5.17 QALYs with the SoC. The resulting incremental cost-effectiveness ratio for the prognostic test versus the SoC was $35,867/QALY gained. One-way sensitivity analyses indicated the model was most sensitive to the utility of patients without recurrence after ACT and the ACT treatment benefit. Probabilistic sensitivity analysis indicated the prognostic test was cost-effective in 65.5% of simulations at a willingness to pay of $50,000/QALY. CONCLUSION: The study suggests using a prognostic test to guide ACT decisions in early-stage NSCLC is potentially cost-effective compared with using the SoC based on globally accepted willingness-to-pay thresholds. IMPLICATIONS FOR PRACTICE: Providing prognostic information to decision makers may help some patients with high-risk early stage non-small cell lung cancer receive appropriate adjuvant chemotherapy while avoiding the associated toxicities and costs in patients with low-risk disease. This study used an economic model to assess the effectiveness and costs associated with using a prognostic test to guide adjuvant chemotherapy decisions compared with the current standard of care in patients with non-small cell lung cancer. When compared with current standard care, the prognostic test was potentially cost effective at commonly accepted thresholds in the U.S. This study can be used to help inform decision makers who are considering using prognostic tests.

Response monitoring, tolerability, and effectiveness of imatinib treatment for chronic myeloid leukemia in a retrospective research database.

Retrospective review of imatinib monitoring through electronic health records (EHR) can provide valuable insight into the current management of chronic myelogenous leukemia (CML). This study retrospectively reviewed EHRs from 2001 to 2010 of patients with chronic phase CML (CP-CML) treated with first-line imatinib. Chart evaluations included a review of cytogenetic and molecular testing, overall survival, adverse drug events (ADEs), and therapy modifications. A total of 54 patients with CP-CML were treated with first-line imatinib and had either cytogenetic or molecular testing within 18 months of imatinib initiation. Within the first 18 months of treatment, 33 of 45 patients (73%) undergoing cytogenetic testing experienced a complete cytogenetic response (median, 241 days; range, 110-542 days) and 24 of 48 patients (50%) receiving molecular testing achieved at least a major molecular response (median, 253 days; range, 99-546 days). The average number of cytogenetic and molecular tests conducted within the first 18 months was 2.5 and 3.8, respectively. Nineteen of 54 (35%) had a dose increase of imatinib (>400 mg; median, 329 days; range, 21-1968 days). The 5-year estimated overall survival rate was 88.5%. Between 2006 and 2010 (n=30; 56%), 7 patients (23%) transitioned to dasatinib or nilotinib (median, 399 days from diagnosis; range, 180-1046 days) because of suboptimal response or treatment failure (n=5) and imatinib ADEs (n=2). Forty-six imatinib-associated ADEs occurred in 31 patients (57%), of which 10 (32%) received dose reductions (median, 52 days) and 6 (19%) had discontinuations (median, 139 days). Closely monitored patients with CML treated with imatinib at an NCCN Member Institution experienced outcomes comparable to those reported in key clinical trials.

New therapies for treating Down syndrome require quality of life measurement.

Down syndrome (DS) is the most common genetic cause of cognitive deficits. Using mouse models and therapies for Alzheimer disease, researchers are exploring therapies that may improve cognitive function in people with DS. These developments shift the health economic paradigm of understanding DS from determining the appropriate screening tool to the effect of therapy on quality of life in those with DS. To date, there are no validated quality of life instruments for DS. Research should begin to develop instruments that can evaluate changes in quality of life in therapeutic trials and beyond.

Use of clomiphene citrate in the University of Utah Community Clinics.

OBJECTIVE: To determine patterns of usage of clomiphene citrate (CC) by primary care providers (obstetrician-gynecologists, family physicians, and other providers) within University of Utah Community Clinics. STUDY DESIGN: We performed a retrospective chart review (n = 79) and followup telephone survey of patients (n = 43) who were prescribed CC in the University of Utah Community Clinics in 2006. RESULTS: Most women who were prescribed CC had appropriate indications for therapy (65% with a diagnosis related to irregular menses and 33% with a diagnosis of female infertility), but there was variable and inconsistent monitoring of ovulation (much of which was apparently initiated by the patients). In the interview, 24 of the women (56%) said they would be fine having twins, and 14 (33%) said they would prefer to have twins if possible. CONCLUSION: In this primary care setting, clomiphene was prescribed for appropriate indications, but the monitoring of treatment could be improved. The preference of some patients for twin gestations represents a challenge for optimum clinical care and public health.

Cost-effectiveness of the tubeless automated insulin delivery system vs standard of care in the management of type 1 diabetes in the United States.

BACKGROUND: A tubeless, on-body automated insulin delivery (AID) system (Omnipod 5 Automated Insulin Delivery System) demonstrated improved glycated hemoglobin A1c levels and increased time in range (70 mg/dL to 180 mg/dL) for both adults and children with type 1 diabetes in a 13-week multicenter, single-arm study. OBJECTIVE: To assess the cost-effectiveness of the tubeless AID system compared with standard of care (SoC) in the management of type 1 diabetes (T1D) in the United States. METHODS: Cost-effectiveness analyses were conducted from a US payer's perspective, using the IQVIA Core Diabetes Model (version 9.5), with a time horizon of 60 years and an annual discount of 3.0% on both costs and effects. Simulated patients received either tubeless AID or SoC, the latter being defined as either continuous subcutaneous insulin infusion (86% of patients) or multiple daily injections. Two cohorts (children: <18 years; adults: ≥18 years) of patients with T1D and 2 thresholds for nonsevere hypoglycemia (nonsevere hypoglycemia event [NSHE] <54 mg/dL and <70 mg/dL) were considered. Baseline cohort characteristics and treatment effects of different risk factors for tubeless AID were sourced from the clinical trial. Utilities and cost of diabetes-related complications were obtained from published sources. Treatment costs were derived from US national database sources. Scenario analyses and probabilistic sensitivity analyses were performed to test the robustness of the results. RESULTS: Treating children with T1D with tubeless AID, considering an NSHE threshold of less than 54 mg/dL, brings incremental life-years (1.375) and quality-adjusted life-years (QALYs) (1.521) at an incremental cost of $15,099 compared with SoC, resulting in an incremental cost-effectiveness ratio of $9,927 per QALY gained. Similar results were obtained for adults with T1D assuming an NSHE threshold of less than 54 mg/dL (incremental cost-effectiveness ratio = $10,310 per QALY gained). Furthermore, tubeless AID is a dominant treatment option for children and adults with T1D assuming an NSHE threshold of less than 70 mg/dL compared with SoC. The probabilistic sensitivity analyses results showed that compared with SoC, in both children and adults with T1D, tubeless AID was cost-effective in more than 90% of simulations, assuming a willingness-to-pay threshold of $100,000 per QALY gained. The key drivers of the model were the cost of ketoacidosis, duration of treatment effect, threshold of NSHE, and definition of severe hypoglycemia. CONCLUSIONS: The current analyses suggest that the tubeless AID system can be considered a cost-effective treatment compared with SoC in people with T1D from a US payer's perspective. DISCLOSURES: This research was funded by Insulet. Mr Hopley, Ms Boyd, and Mr Swift are full-time Insulet employees and own stock in Insulet Corporation. IQVIA, the employer of Ms Ramos and Dr Lamotte, received consulting fees for this work. Dr Biskupiak is receiving research support and consulting fees from Insulet. Dr Brixner has received consulting fees from Insulet. The University of Utah has received research funding from Insulet. Dr Levy is a consultant with Dexcom and Eli Lilly and has received grant/research support from Insulet, Tandem, Dexcom, and Abbott Diabetes. Dr Forlenza conducted research sponsored by Medtronic, Dexcom, Abbott, Tandem, Insulet, Beta Bionics, and Lilly. He has been speaker/consultant/advisory board member for Medtronic, Dexcom, Abbott, Tandem, Insulet, Beta Bionics, and Lilly.

Assessing adherence-based quality measures in epilepsy.

OBJECTIVE: To examine the relationship of three alternative measures of adherence with seven negative outcomes associated with epilepsy for development of a quality measure in epilepsy. DESIGN: Retrospective cohort analysis. SETTING: PharMetrics national claims database. PARTICIPANTS: Patients in the PharMetrics database for the years 2004-08 taking antiepileptic drugs. INTERVENTION: None. MAIN OUTCOME MEASURES: For each definition of adherence, the odds ratios (ORs) comparing non-adherent with adherent groups were assessed for consistency and direction for the number of hospital admissions, emergency room (ER) visits, head injuries including traumatic brain injuries, falls, motor vehicle accidents (MVAs), fractures and a 'seizure' outcome defined as hospital admissions or ER visits with a primary diagnosis of epilepsy or convulsions. RESULTS: The inclusion criteria were met by 31 635 individuals. In the multivariate analysis, the adherent group had lower odds of hospital admissions with ORs for the eight specifications ranging from 0.729 to 0.872 and ER visits where ORs for the eight specifications ranged from 0.750 to 0.893. The eight ORs for head injuries ranged from 0.647 to 0.888. For fractures, the ORs ranged from 0.407 to 0.841. Our proxy for seizure was inconsistently associated with adherence status. CONCLUSIONS: All the adherence measures defined non-adherent groups that were associated with negative outcomes in epilepsy.

The Rise of Prescription Digital Therapeutics in Behavioral Health.

Medicine is evolving to incorporate digital technologies of all kinds-technologies that may improve patient health, reduce clinician workload, lower costs, reduce health disparities, and expand access to needed treatments. Prescription digital therapeutics (PDTs) are an emerging technology with particular potential. These are software-based treatments delivered on mobile devices that address the behavioral dimensions of many diseases and conditions. Unlike health and wellness apps, PDTs are rigorously evaluated for safety and effectiveness and are authorized by the US Food and Drug Administration (FDA). Nine PDTs are currently authorized to treat conditions such as substance use disorders, attention-deficit disorder, and chronic insomnia. The findings reported in two recent research papers published by Advances in Therapy related to use of PDTs for substance use disorder and opioid use disorder provide real-world evidence of clinical and cost effectiveness, strengthening the evidence base for these technologies and suggesting a role for these technologies in the efforts to help patients recover from these often-chronic and deadly conditions.

Clinical risk factors for fracture among postmenopausal patients at risk for fracture: a historical cohort study using electronic medical record data.

Osteoporosis represents a growing health burden, but recognition and screening rates are low. Electronic reminders for osteoporosis have been beneficial but are not based on clinical risk factors. Available risk screening tools may contain useful constructs for creating risk-based electronic medical record (EMR) reminders. Using a cohort study design among women ≥50 years with osteoporosis or osteoporosis risk, we searched the EMR for five World Health Organization (WHO) clinical risk factors including older age, lower body mass index (BMI), low bone mineral density (BMD), history of fracture since age 50, and maternal history of osteoporosis or fracture. Rates of reporting were lower than expected for BMD (6.8%), personal history of fracture (3.5%), and maternal history of fracture (0.3%). Despite the limitations, the EMR data were useful for identifying women at highest risk for fracture. Some evidence of bias in reporting rates was present. EMR data can be useful for identifying high fracture risk patients.

Hemorrhagic and thrombotic events associated with generic substitution of warfarin in patients with atrial fibrillation: a retrospective analysis.

BACKGROUND: Substitution of generic warfarin for imprint warfarin (Coumadin; DuPont/Bristol-Myers Squibb) has been a controversial issue due to bioavailability and bioequivalence concerns. OBJECTIVE: To assess the risk of thrombotic and hemorrhagic events following substitution of warfarin formulations in patients with atrial fibrillation (AF). METHODS: Historical cohort analysis was performed using a commercial insurance claims database. Adults with a diagnosis of AF between January 2003 and December 2007, with 16 or more months of continuous eligibility, a warfarin prescription within 30 days after index AF diagnosis, and at least 3 warfarin prescription fills during the follow-up period were included. Individuals with AF diagnosis or warfarin prescription during the pre-index period were excluded. Cox proportional hazard regression models controlling for sex and baseline comorbidities (Charlson comorbidity index, CCI) were used to evaluate the risks of thrombotic and hemorrhagic events following warfarin formulation switches. RESULTS: Of 37,756 subjects included in the analysis (mean age 70.96 years, 42.3% females), 12,996 (34.4%) switched warfarin formulations, 20,292 (53.7%) used only 1 generic product, and 4468 (11.8%) used only Coumadin during follow-up. Compared with continued use of Coumadin, switching from that product to the generic formulation was associated with a significantly higher risk of thrombotic events (HR = 1.81; 95% CI 1.42 to 2.31). Similar findings were observed for switching from generic warfarin to Coumadin (HR = 1.76; 95% CI 1.35 to 2.30), and from 1 generic to another generic product (HR = 1.89; 95% CI 1.57 to 2.29). Similarly, switching from Coumadin to generic warfarin (HR = 1.51; 95% CI 1.17 to 1.93), generic warfarin to Coumadin (HR = 1.60; 95% CI 1.23 to 2.1), and from 1 generic to another generic product (HR = 1.74; 95% CI 1.45 to 2.11) were associated with significantly higher risk of hemorrhage than remaining on Coumadin. CONCLUSIONS: Switching warfarin formulations exposed patients with AF to a higher risk of bleeding events compared to remaining on a single product. Maintaining patients on a product with consistent bioavailability may optimize the risk-benefit balance of anticoagulation therapy.

Can Cost-effectiveness Analysis Inform Genotype-Guided Aspirin Use for Primary Colorectal Cancer Prevention?

BACKGROUND: Inherited genetic variants can modify the cancer-chemopreventive effect of aspirin. We evaluated the clinical and economic value of genotype-guided aspirin use for colorectal cancer chemoprevention in average-risk individuals. METHODS: A decision analytical model compared genotype-guided aspirin use versus no genetic testing, no aspirin. The model simulated 100,000 adults ≥50 years of age with average colorectal cancer and cardiovascular disease risk. Low-dose aspirin daily starting at age 50 years was recommended only for those with a genetic test result indicating a greater reduction in colorectal cancer risk with aspirin use. The primary outcomes were quality-adjusted life-years (QALY), costs, and incremental cost-effectiveness ratio (ICER). RESULTS: The mean cost of using genotype-guided aspirin was $187,109 with 19.922 mean QALYs compared with $186,464 with 19.912 QALYs for no genetic testing, no aspirin. Genotype-guided aspirin yielded an ICER of $66,243 per QALY gained, and was cost-effective in 58% of simulations at the $100,000 willingness-to-pay threshold. Genotype-guided aspirin was associated with 1,461 fewer polyps developed, 510 fewer colorectal cancer cases, and 181 fewer colorectal cancer-related deaths. This strategy prevented 1,078 myocardial infarctions with 1,430 gastrointestinal bleeding events, and 323 intracranial hemorrhage cases compared with no genetic testing, no aspirin. CONCLUSIONS: Genotype-guided aspirin use for colorectal cancer chemoprevention may offer a cost-effective approach for the future management of average-risk individuals. IMPACT: A genotype-guided aspirin strategy may prevent colorectal cancer, colorectal cancer-related deaths, and myocardial infarctions, while minimizing bleeding adverse events. This model establishes a framework for genetically-guided aspirin use for targeted chemoprevention of colorectal cancer with application toward commercial testing in this population.

Impact of body mass index on the incidence of cardiometabolic risk factors in ambulatory care settings over 5 years or more.

OBJECTIVE: This study was performed to evaluate the association of body mass index (BMI) with the incidence of cardiometabolic risk factors in ambulatory care electronic medical records (EMRs) over 5 years or more. DESIGN: A retrospective cohort of normal versus obese patients. SUBJECTS: Subjects>or=18 years were identified between 1996 and 2005. MEASUREMENTS: Patients were categorized as either normal weight (18 kg/m227 kg/m2) based on baseline BMI (measured 395 days or more after first EMR activity). Outcomes included development, at least 180 days after the first BMI reading date, of four cardiometabolic risk factors (elevated triglycerides, low high-density lipoprotein cholesterol [HDL-C], hypertension, or type 2 diabetes) determined from ICD-9 code, prescribed drug, or biometric reading. Logistic regression estimated the odds of developing cardiometabolic risk factors, alone and combined for normal versus obese patients forward for at least 5 years. RESULTS: Seventy-one percent were female, mean age was 43.5 years, and 37.6% had a baseline BMI>27 kg/m2. Comparing obese versus normal weight patients, adjusted odds ratios for the incidence of elevated triglycerides, hypertension, diabetes, and low HDL-C were 2.1 (95% confidence interval [95% CI] 1.9-2.3), 2.2 (95% CI 2.1-2.4), 2.3 (95% CI 2.0-2.7), and 2.2 (95% CI 2.0-2.4), respectively. Adjusted odds ratios of developing one and all four new risk factors were 1.9 (95% CI 1.8-2.1) and 7.9 (95% CI 5.9-10.5), respectively. CONCLUSION: Obese patients are approximately twice as likely to develop cardiometabolic risk factors compared with those having normal weight over 5 or more years.

Predicting Optimal Hypertension Treatment Pathways Using Recurrent Neural Networks.

BACKGROUND: In ambulatory care settings, physicians largely rely on clinical guidelines and guideline-based clinical decision support (CDS) systems to make decisions on hypertension treatment. However, current clinical evidence, which is the knowledge base of clinical guidelines, is insufficient to support definitive optimal treatment. OBJECTIVE: The goal of this study is to test the feasibility of using deep learning predictive models to identify optimal hypertension treatment pathways for individual patients, based on empirical data available from an electronic health record database. MATERIALS AND METHODS: This study used data on 245,499 unique patients who were initially diagnosed with essential hypertension and received anti-hypertensive treatment from January 1, 2001 to December 31, 2010 in ambulatory care settings. We used recurrent neural networks (RNN), including long short-term memory (LSTM) and bi-directional LSTM, to create risk-adapted models to predict the probability of reaching the BP control targets associated with different BP treatment regimens. The ratios for the training set, the validation set, and the test set were 6:2:2. The samples for each set were independently randomly drawn from individual years with corresponding proportions. RESULTS: The LSTM models achieved high accuracy when predicting individual probability of reaching BP goals on different treatments: for systolic BP (<140 mmHg), diastolic BP (<90 mmHg), and both systolic BP and diastolic BP (<140/90 mmHg), F1-scores were 0.928, 0.960, and 0.913, respectively. CONCLUSIONS: The results demonstrated the potential of using predictive models to select optimal hypertension treatment pathways. Along with clinical guidelines and guideline-based CDS systems, the LSTM models could be used as a powerful decision-support tool to form risk-adapted, personalized strategies for hypertension treatment plans, especially for difficult-to-treat patients.

Results of a retrospective, observational pilot study using electronic medical records to assess the prevalence and characteristics of patients with resistant hypertension in an ambulatory care setting.

BACKGROUND: Resistant hypertension, or failure to attain blood pressure (BP) goals while treated with > or = 3 antihypertensives (including a diuretic), occurred in 15% to 18% of patients in prospective cohort trials. OBJECTIVES: The aims of this work were to identify the prevalence of resistant hypertension in an ambulatory care setting and to describe the characteristics of patients with resistant hypertension. METHODS: Adults with hypertension were retrospectively identified in a US electronic medical record from November 1, 2002, through November 30, 2005. Antihypertensive treatment and BP values were assessed to identify those with BP > or = 140/90 mm Hg (>130/80 mm Hg for those with diabetes mellitus or kidney disease). Patients treated with > or = 3 agents (including a thiazide) who had > or = 1 BP level above target were classified as having resistant hypertension. Baseline characteristics were compared between those with and those without resistant hypertension. RESULTS: Of 29,474 study patients aged > or = 18 years, 21,460 (72.8%) had > or = 1 prescription order for an antihypertensive and 19,202 (65.1%) had a follow-up BP level above target. The analysis found that 2670 patients (9.1% overall or 12.4% of those who were treated) were classified as having resistant hypertension. Relative to those without resistant hypertension, a greater proportion of those with resistant hypertension were female (65.6% vs 60.5%), were older (66.2 vs 63.0 years), had a higher body mass index (31.6 vs 30.4 kg/m(2)), had higher baseline BP levels (148/81 vs 138/80 mm Hg), and had higher rates of diabetes mellitus (35.2% vs 20.1%) or kidney disease (4.9% vs 2.7%) than those without resistant hypertension (all comparisons, P < 0.001). CONCLUSIONS: This retrospective, observational pilot study of usual community practice supports the findings from prospective trials that resistant hypertension is an important clinical problem. More effective management is needed to enable patients with, or at risk for, resistant hypertension to achieve BP goals.

Immunotargeted therapy in melanoma: patient, provider preferences, and willingness to pay at an academic cancer center.

New melanoma therapies have shifted the expectations of patients and providers. Evaluating the impact of treatment characteristics may enhance shared decision making. A survey, including a discrete choice experiment, was utilized to evaluate perceived trade-offs of different melanoma treatments and to estimate out-of-pocket (OOP) willingness-to-pay (WTP) thresholds (January 2016 to March 2016). Participants included patients with melanoma at Huntsman Cancer Institute and their cancer care providers. Stakeholder focus groups were conducted to identify treatment attributes. Descriptive and comparative statistics and multinomial logit model were used to evaluate responses. Response rates were 41.9% (N = 220) for patients and 37.7% (N = 20) for providers. Immunotherapy and targeted therapy attributes considered important by participants were overall survival, immunotherapy-related side effects, and skin toxicities. Patients and providers had significantly different views of quality-of-life expectations, anxiety toward melanoma, trust to make treatment decisions, sharing concerns about treatment, time to discuss treatment, understanding OOP costs, and willingness to undergo/recommend treatment (half of the patients would undergo treatment if it was effective for > 24 months). Among patients, the average monthly OOP WTP for combination immunotherapy with nivolumab + ipilimumab was $ 2357 and for BRAF/MEK inhibitor was $1648. Among providers, these estimates were $ 2484 and $1350, respectively. Discordance existed between patients' and providers' perceptions about quality of life expectations, degree of anxiety, sharing of opinions, and progression-free survival. Our study suggests that patients and providers exhibit a higher OOP WTP for combination immunotherapy treatment compared with BRAF/MEK inhibitors, influenced predominately by overall survival expectations.