Citations

Background: Blood pressure (BP) measurement is a national core quality measure for hypertension care and hypertension control rates remain a major performance measure. It remains unclear whether improving measurement directly results in better control rates in hypertension management. Purpose: To utilize electronic medical records to explore the relationship between measurement of blood pressure and hypertension control rates among 4 eligible primary care providers groups - Primary Care Internal Medicine (PCIM), Family medicine (FM), General Internal Medicine (GIM), Preventive Medicine (PREV) - and 2 eligible specialist groups - Cardiology (CARD), Nephrology (NEPH) at an academic group medical practice. Methods: A two year cross sectional study involving adults seen by eligible primary or specialist providers at 2 or more office visits with a hypertension ICD-9 code in two years with at least one office visit in the measurement year. We measured the proportion of patients who had their BP measured at their last hypertension visit (LHV) in 2009 and 2010. We compared measurement rates with control rates as defined by the proportion of hypertension patients with BP < 140/90 mmHg at their LHV. Results: In 2009, 84.2% of 17989 patients (95% CI 83.6 - 84.7%) had their BP measured at their LHV compared to 85.3% (95% CI 84.8 - 85.8%) of 17992 patients in 2010, an increase of 1.2% (p=0.0026). Measurement rates varied widely across the different provider groups. PCIM, a high performing group, had significant improvement in measurement rates from 2009 to 2010 and demonstrated improvement in control rates. Lower performing groups, Nephrology and GIM, had significant improvement in measurement but did not see a direct translation to improved control rates. There was an associated worsening of the control rates for Preventive medicine along with a decrease in the measurement rates from 2009 to 2010. Conclusion: High BP measurement rates are associated with high hypertension control rates. Prioritizing BP measurement may result in improved intermediate outcomes in hypertension management.

Background: The diagnosis of hypertension requires systolic blood pressure (SBP) ≥ 140 mmHg or diastolic blood pressure (DBP) ≥ 90 mmHg on at least 2 different occasions. Therefore, there is the possibility of patients with elevated BP remaining undiagnosed if not seen by the same provider. Purpose: To utilize electronic medical records (EMR) to identify patients not previously diagnosed with hypertension that have elevated blood pressure meeting criteria for a diagnosis of hypertension using a threshold of SBP ≥ 140mmHg or DBP ≥ 90 mmHg (high BP) on 2 or more occasions. Methods: This was a cross sectional design utilizing retrospective multi-year billing and clinical data from a large multi-specialty center in the Midwest. Using electronic records of all outpatient visits in each year from 2009 - 2011, patients with at least 2 visits with SBP ≥ 140mmHg or DBP ≥ 90 mmHg (2HBP) in the measurement year were identified. These patients were compared with previously identified cohorts of known hypertension patients (Known HTN) compiled using the EMR problem list. A sensitivity analysis was done using patients with high BP at 2 consecutive visits (2CHBP) and also those with high BP at 3 consecutive visits (3CHBP). We compared proportions of patients with high BP without a prior diagnosis of hypertension (UDHTN). Results: The proportion of patients with SBP ≥ 140mmHg or DBP ≥ 90 mmHg without a prior diagnosis of hypertension (UDHTN) when compared to the cohort of known patients with a diagnosis of hypertension (Known HTN) was 25% in 2009, 26% in 2010, and 28% in 2011 in the 2CHBP cohort compared to 27% in 2009, 28% in 2010, and 30% in 2011 in the 2HBP cohort and 18% in 2009, 19% in 2010 and 23% in 2011 in the 3CHBP cohort. Conclusion: About a quarter of patients meeting current thresholds on multiple and consecutive visits did not have a known diagnosis of hypertension. The use of EMR can identify these patients for commencement of appropriate management. Table 1

Background: Hypertension (HTN) control rate is a core clinical quality measure. It is presently assessed by manual review of a random sample of patients with HTN billing claims. There is an increasing push by regulators towards the use of electronic medical records (EMR) to assess quality of care. Purpose: To use EMR to obtain a more in-depth assessment of quality of hypertension care. Methods: Cross sectional study involving adults with HTN seen at 2 or more office visits in 2009 by eligible primary or specialist providers at a large medical group practice. We measured the proportion of HTN patients with blood pressure (BP) at goal (BP < 140/90 mm Hg) at their last hypertension visit (LHV). Results: Of a total of 10,401 patients, 5970 (57%) were controlled and 1959 (19%) were uncontrolled at their LHV. Control could not be assessed in 2472 (24%) as BP values were unavailable from the vital signs section of the visit notes in the EMR. Of a random sample of 250 patients with unavailable BP, only 94 (37.6%) had BP values documented in other parts of the visit note. In 29 patients (11.6%) billing for HTN was done without adequate evidence that it was addressed at that visit. Control rates were highest for primary care providers where measurement and documentation of BP was a focus - Family Medicine 77% controlled, 1% unavailable; Primary Care Internal Medicine 71% controlled, 4% unavailable. A considerable proportion of patients in the other four provider groups did not have BP available from their last hypertension visit - Cardiology 59% controlled, 22% unavailable; Nephrology 38% controlled, 47% unavailable; Preventive Medicine 48% controlled, 39% unavailable; General Internal Medicine 41% controlled, 45% unavailable. Control rates were similar across provider groups when patients with unavailable BP were excluded: Family Medicine 78%, Primary Care 74%, Cardiology 75%, Nephrology 73%, Preventive Medicine 79%, and General Medicine 75%. Conclusions: Up to a quarter of HTN patients did not have properly documented BP in the EMR at their LHV. For those with measurements recorded, control rates were similar across primary care and specialty clinics, but measurement rates were higher for primary care practices. Use of the EMR facilitates efficient and granular assessment of the measurement process and control rates for HTN among various provider groups.

Introduction: Patients with hypertension (HTN) may remain undiagnosed as the diagnosis requires systolic blood pressure (SBP) ≥ 140 mmHg or diastolic blood pressure (DBP) ≥ 90 mmHg on ≥ 2 different occasions. Hypothesis: We sought to evaluate outcomes of patients without diagnosed hypertension who have elevated BP meeting current thresholds for hypertension on 2 consecutive episodes. Methods: Together with retrospective billing and clinical data, electronic records of all outpatient visits in 2009 were used to identify 24,277 patients with 2 consecutive visits (2CHBP) with SBP ≥ 140mmHg or DBP ≥ 90 mmHg and were compared with a previously identified cohort of 53,998 known hypertension patients. Among the 2CHBP group, 6,071 (25%) were identified without a prior diagnosis of hypertension and were categorized as undiagnosed hypertension. They were compared with patients with known hypertension who had ≥ 1 visit in 2009. Cross-sectional analysis of cardiovascular comorbidities and proportional hazards for survival were done. Results: Of 5,978 undiagnosed HTN patients, 49% were female compared to 51% of 10,311 known HTN. In the undiagnosed HTN group, 19.5% were ≥ 80 years compared to 30.4% of known HTN patients. Cardiovascular comorbidities were generally lower in the undiagnosed HTN group compared to the known HTN group - heart failure (7% v 8%; OR 0.88, 95% CI: 0.77 - 0.99; p < 0.038), atrial fibrillation (11% v 12%, OR 0.88 95% CI 0.79 - 0.97) and coronary artery disease (17% v 26%, OR 0.57 95% CI 0.52 - 0.61). However after a four year followup, mortality was higher in the undiagnosed HTN group with unadjusted hazard ratio HR 1.4 (95% CI 1.29 - 1.60, p<0.0001) and HR 2.41 (2.16 -2.68, p<0.0001) when adjusted for age, sex, heart failure and diabetes. Conclusions: Over a quarter of patients meeting current thresholds on 2 consecutive visits did not carry a known diagnosis of hypertension. Although younger and with less cardiovascular comorbidities than those with diagnosed hypertension, mortality after 4 years was significantly higher in those with undiagnosed hypertension. Electronic records can be used to identify these high risk patients.

7022 Background: Philadelphia-like Acute Lymphoblastic Leukemia (Ph-like ALL) is a high-risk subset of adult ALL. Until recently, there has not been a systematic platform to recognize this entity in clinical practice. Furthermore, data regarding the role of allogeneic hematopoietic cell transplantation (allo-HCT) is lacking. We conducted this study to identify patients with Ph-like ALL and describe their outcomes in comparison to Ph+ and Ph- ALL with emphasis on the role of allo-HCT. Methods: To identify cases of Ph-like ALL, available diagnostic cytogenetic pellets for patients in the Mayo Clinic ALL cohort (N=365) were tested using a targeted fluorescence in situ hybridization (FISH) panel developed by the Mayo Clinic Genomics Laboratory and includes probes to detect Ph-like-specific rearrangements (i.e., ABL1, ABL2, PDGFRB, JAK2 and CRLF2). Results: Thirty-three (9%) patients with Ph-like ALL were identified, the remaining patients were classified as Ph+ (N=132, 36%) or Ph- ALL (N=200, 55%). Patients with Ph-like ALL were younger (Median: 39 vs. 50 vs. 49 years, P=.01), had higher WBC (Median: 27.9 vs. 21.5 vs. 4.5 x109/L, P<.001), were less likely to achieve CR (91% vs. 99% vs. 96%, P=.02), more likely to be MRD+ (64% vs. 34% vs. 36%, P=.03), had a higher relapse rate (5-year: 39% vs. 24% vs. 38%, P=.01) and lower OS (5-year: 41% vs. 64% vs. 49%, P=.02), see Table. Patients who achieved MRD negativity had better OS (MRD+ vs MRD-, P=.01). Importantly, no statistically significant difference in OS, relapse or non-relapse mortality were noted between the 3 groups in patients who underwent allo-HCT in CR1. Conclusions: Ph-like ALL is a high risk subgroup with increased prevalence in younger adults. Allo-HCT appears to offset the poor prognosis associated with this entity. A targeted FISH panel offers timely recognition of this entity in a clinical setting.[Table: see text]

5554 Background: A better understanding regarding the burden of treatment side effects in patients with gynecological malignancies could help guide symptom interventions and oncologic therapy decision-making. We aim to inform understanding of symptom burden in epithelial ovarian cancer (EOC) by analyzing patient-reported symptom data from patients treated for this condition over a 16-month period. Methods: Patients receiving medical oncology care at Mayo Clinic Rochester and at Midwest Mayo Clinic Health System community sites have received symptom-focused surveys prior to each medical oncology visit since March 28, 2019 through the Enhanced Electronic Health Record Facilitated Cancer Symptom Control Study (E2C2). These surveys, administered either through the electronic medical record portal or on a clinic tablet prior to each oncology office visit, no more frequently than every 2 weeks, include six linear analogue scales measuring sleep disturbance, pain, anxiety, emotional distress, and fatigue (SPADE), as well as physical dysfunction on a scale of 0 (none) to 10 (as bad as you can imagine). Scores of 0-3 were considered mild symptoms, 4-6 moderate symptoms, and 7-10 severe symptoms. We collected survey results from March 28, 2019 to July 20, 2020 for patients with EOC and reviewed the number of surveys per patient in addition to the average symptom scores. Results: From March 2019 to July 2020, for patients with EOC, there were 2974 encounter-based surveys from 762 patients. The number of surveys completed by each patient ranged from 1-20. The following number of patients returned the correlating number of surveys: 1 survey:240 patients; 2 surveys:145; 3 surveys:79; 4 surveys:56; 5 surveys:58; 6 surveys:45; 7 surveys:38; 8 surveys:27; 9 surveys:22; ≥10 surveys:52. The average score from all surveys for each symptom was: 2.41 for sleep disturbance, 2.03 for pain, 2.32 for anxiety, 1.97 for emotional distress, 3.26 for fatigue, and 2.50 for physical dysfunction. Please see the table for the proportion of surveys that reported symptoms as mild, moderate, or severe. Conclusions: Fatigue and physical dysfunction were reported most frequently in patients with EOC, while emotional distress and pain were reported least frequently. 20% of surveys reported moderate to severe emotional distress, while 40% reported moderate to severe fatigue. A targeted approach to symptom management is needed for patients undergoing EOC evaluation and treatment. Our next steps in this analysis include an assessment of potential predictors of greater symptom burden (e.g., specific treatments, age, and other clinical and sociodemographic characteristics). Clinical trial information: NCT03892967. [Table: see text]

2014 Background: The cyclin D-CDK4/6-Rb pathway is activated in most glioblastomas. Abemaciclib is a potent CDK4/6 inhibitor with good brain penetration approved for HR+/HER2- breast cancer. In order to efficiently evaluate the potential impact of abemaciclib on overall survival (OS) in newly diagnosed glioblastoma and to simultaneously develop information regarding potential genomic biomarker associations, abemaciclib was included as an arm on the Individualized Screening Trial of Innovative Glioblastoma Therapy (INSIGhT) trial. INSIGhT is a phase II platform trial using response adaptive randomization and deep genomic profiling to more efficiently test experimental agents in MGMT unmethylated glioblastoma and potentially accelerate identification of novel therapies for phase III testing. Initial randomization was equal between abemaciclib, control, and two other experimental arms but subsequent randomization was adapted based on efficacy as determined by progression-free survival (PFS). Ineffective arms were discontinued and new arms added by protocol amendment. We report preliminary results for the abemaciclib arm which has completed accrual. Methods: Patients with newly diagnosed MGMT-unmethylated glioblastoma were randomized to receive either radiotherapy with concomitant and adjuvant temozolomide at standard doses or standard radiochemotherapy followed by adjuvant abemaciclib (150-200 mg orally BID). Treatment continued until progression or development of unacceptable toxicities. The primary endpoint was OS which was assessed using the log-rank test estimated via the Kaplan Meier method using a type I error of 5%. The hazard ratio (HR) was estimated using a cox proportional hazards model. Association between abemaciclib efficacy and cyclin D-CDK4/6-Rb pathway genomic alterations was also investigated. Results: There were 142 patients (69 control; 73 treated with abemaciclib). Abemaciclib was generally well-tolerated with no new toxicity signals identified. PFS was significantly longer (HR 0.67; p = 0.03, logrank test) with abemaciclib (median 6.54 months) compared to the control arm (median 5.88 months). For patients with activation of the CDK4 pathway the PFS HR was 0.64 (p-value = 0.04). However, there was no significant improvement in overall survival (HR 0.9; p-value > 0.05) between abemaciclib (median 15.5) compared to the control arm (median 15.5). Conclusions: Abemaciclib was well-tolerated and prolonged PFS but there is no evidence of an overall survival improvement compared to standard radiochemotherapy. Clinical trial information: NCT02977780.

2006 Background: Adaptive randomization adjusts enrollment rates based upon early trial results, which can allow for decreased enrollment for therapies less likely to meet the primary endpoint of a trial. CC-115, a CNS-penetrant, oral inhibitor of mammalian target of rapamycin kinase (mTOR) and deoxyribonucleic acid-dependent protein kinase (DNA-PK), was evaluated in the Individualized Screening Trial of Innovative Glioblastoma Therapy (INSIGhT) trial. As CC-115 was discontinued due to concerns about toxicity and unfavorable risk-to-benefit ratio, we sought to investigate the impact of adaptive randomization in its testing. Methods: In INSIGhT, adults with newly diagnosed MGMT-unmethylated glioblastoma and available genomic data are adaptively randomized to an experimental arm or the control arm of standard radiotherapy with concurrent and adjuvant temozolomide. Patients randomized to CC-115 received it (10mg po BID) with radiotherapy and as adjuvant monotherapy, and a safety lead-in 3+3 design was used for this arm. By simulating the INSIGhT trial with standard uniform randomization, we estimated the reduction of enrollment rate and sample size of the CC-115 arm that was attributable to adaptive randomization. Results: Twelve patients were randomized to CC-115; 58% (n = 7) patients had possible treatment-related CTCAE grade > 3 toxicity. Compared to the control arm, there was no significant difference in progression-free survival (PFS, HR 0.66, 95% CI 0.32-1.36, p = 0.3) or overall survival (OS, HR 0.93, 95% CI 0.43-2.03, p = 0.8). Based on early PFS results, randomization probability to CC-115 decreased from 25% to 16%. At the time of the CC-115 arm closure, 14% of enrolled INSIGhT patients had been randomized to this arm. Compared to average expected enrollment by standard randomization, the use of adaptive randomization decreased the number of patients randomized to CC-115 by 50% (12 patients vs. 18 patients [95% CI 11-25 patients]). Conclusions: The INSIGhT trial, designed with adaptive randomization, facilitated more efficient testing of CC-115 and decreased the number of patients allocated to the CC-115 arm relative to a standard randomization design. Clinical trial information: NCT02977780.

Background: Electronic health records (EHRs) may help enable reliable, rapid data management for many uses, such as facilitating communication of advance care planning (ACP). However, issues with validity and accuracy of EHRs hinder the use of ACP information for practical applications. Design: We present a cross-sectional pilot study of 433 older adults with cancer from three large health care systems, participating in an ongoing multisite pragmatic trial (4UH3AG060626-02). We compared data extracted from dedicated structured EHR fields for ACP to a chart review of corresponding ACP documentation contained in the medical chart. Results: Structured ACP data existed for 43.2% of patients and varied by site (25.7% −48.9%). Of the identified structured ACP data elements, 59.2% of recorded elements were correct, 23.7% were incorrect, and 17.1% were duplicates with heterogeneity across sites. Conclusion: Structured ACP data in EHRs were frequently incorrect. This represents a problem for patients and their families, as well as quality improvement and research efforts. Clinical Trials Registration: NCT03609177.

Abstract BACKGROUND NAD+ is required for cell metabolism and DNA repair. It is generated from nicotinic acid (NA) by NAPRT and from Nicotinamide (NAM) by NAMPT. D2HG in IDH-mutant tumors methylates and inactivates NAPRT, increasing dependence on NAMPT. Toxic side effects of NAMPT inhibition can be prevented by NA supplementation in healthy cells without NAPRT methylation. A1326133 is a recently described CNS-penetrant NAMPT inhibitor hypothesized to selectively eliminate IDH-mutant NAPRT-methylated gliomas, likely in combination with other therapies. Our group is looking for biomarkers of drug efficacy to augment individualized therapies. To that end, we sought to identify GBM cell lines with varying sensitivity to NAMPT inhibition. METHODS Human non-immortalized astrocytes and human GBM cell lines were utilized from the Mayo Clinic Glioma patient-derived xenograft resource, including IDH-R132Hmutant lines (GBM164, 196) and IDH-WT lines (GBM6, 12, 76). Cell viability was analyzed after 4days incubation with the NAMPT inhibitor, A1326133 +/- Temozolomide (TMZ) or NA. IC50 for A1326133 was estimated based on intracellular ATP using Cell-Titer-Glo. RESULTS Marked heterogeneity between lines was observed in response to A1326133 +/- NA or TMZ. Sensitive and resistant lines were identified among both IDH-mutant and IDH-WT cell lines. IC50s: GBM164, 12, 6, 196 and 76 were 5.6, 9.3, 39.2, 910, and 9455nM, respectively. NA partially rescued GBM164 by NA (IC50 increased to 20.8nM) but not GBM6 nor 12. IC50 for Human astrocytes was 221.7nM, but &gt;10,000nM with NA. Addition of TMZ did not improve A1326133 efficacy. CONCLUSION Our data illustrate the potential utility of NAMPT inhibition to kill a subset of IDH-WT and IDH mutant lines, but conflict with previously reported TMZ synergy and correlation with mutant IDH. NA may increase safety but could decrease efficacy in certain lines. Ongoing studies seek metabolic biomarkers of therapeutic efficacy to guide individualized therapy with NAMPT inhibitors.