ALBERT

Description: Journal of Medicinal Chemistry DOI: 10.1021/jm300204j

Description: The use of thromboprophylaxis among at-risk groups of inpatients to prevent hospital-associated venous thromboembolism (HA-VTE) has long been considered suboptimal. Little is known, though, whether utilization of anticoagulants in inpatient settings has increased in recent years. The objective of this study was to assess trends in the administration of anticoagulants to inpatients in a sample of US hospitals from 2006 through 2010 and to further evaluate how trends in utilization vary by type of patient group. A comprehensive national database of all-payer billing records from more than 600 US acute care hospitals, the Truven Health MarketScan® Hospital Drugs Database, was accessed for the years 2006 through 2010. Uniquely, this national hospital database contains records on prescription medications administered in the inpatient setting. Data were analyzed for a subset of hospitals for which an indicator of potential record error was zero. Data for this analysis were contributed by 394 hospitals in 2006 and 333 hospitals in 2010. The analysis was restricted to inpatient admissions of longer than 1 day for adult (age ≥ 18 years) patients who were neither admitted from nor discharged to another acute care hospital (i.e., no hospital transfers). Records were excluded for admissions with a diagnosis that could require anticoagulation for treatment, i.e., deep vein thrombosis, pulmonary embolism, atrial fibrillation, stroke, or myocardial infarct. Total admissions included were 3,188,966 in 2006 and 2,554,806 in 2010. For the purposes of this study, records with one or more prescriptions for the following anticoagulants--enoxaparin, dalteparin, fondaparinux, or warfarin--were classified as presumed thromboprophylaxis since conditions for which anticoagulants are prescribed as treatment had been excluded. In addition, administration of unfractionated heparin of 1,000 U or more was considered prophylactic; low-dose heparin prescriptions (〈 1000 U) were assumed to be used as a heparin flush. Anticoagulation prophylaxis rates were assessed for all inpatients and for 5 selected at-risk patient groups based on ICD-9-CM codes used for the same patient groups in Amin A, et al. (2011; 2012): hip/knee surgery, cancer, congestive heart failure (CHF), severe lung disease (including chronic obstructive pulmonary disease), and infectious disease. The associated numbers of admissions in 2010 and the percentages of all admissions for the five at-risk groups are: 52,517 (2.1%) knee/hip, 127,407 (5.0%) cancer, 33,212 (1.3%) severe lung disease, 28,514 (1.1%) CHF, and 27,541 (1.1%) infection. Provisional results indicate that the frequency of administration of thromboprophylaxis in a sample of US inpatient hospitalizations increased over time, from 34.0% in 2006 to 41.40% in 2010, a relative increase of 21.5% in a 4-year period. The use of anticoagulation was highest among major orthopedic surgical patients at each point, 85.97% in 2006 and 87.40% in 2010. The second highest use was observed in hospitalizations for patients with severe lung disease, increasing from 65.33% in 2006 to 69.63% in 2010. Use of anticoagulants for hospitalizations with CHF diagnoses increased from 60.61% in 2006 to 67.99% in 2010. Increases in use of anticoagulation were larger in both absolute and relative terms for two other groups of at-risk hospitalizations. For hospitalizations associated with infectious disease diagnoses, the frequency of use increased from 46.03% in 2006 to 57.71% in 2010, a relative increase of 25.4%. Finally, the largest relative increase in thromboprophylaxis use in at-risk patient groups was observed for hospitalizations associated with cancer diagnoses, among which use increased from 40.52% in 2006 to 52.53% in 2010, a relative increase of 29.6%. These data suggest that substantial increases have occurred in recent years in the frequency with which anticoagulants are prescribed to US inpatients for the prevention of HA-VTE. Additional analyses are being conducted to assess whether increased use of anticoagulants for thromboprophylaxis has been associated with outcomes such as changes in the frequency of in-hospital bleeding events that require treatment. Disclosures: Amin: Johnson & Johnson: Research Funding, Speakers Bureau; BMS/Pfizer: Research Funding, Speakers Bureau.

Description: Background: The increasing incidence in multiple myeloma (MM), coupled with improved efficacy of therapies, warrant population-based studies of diagnosis delay which could lead to disease-related complications. Methods: We analyzed tumor registry data and provider claims in the SEER-Medicare database, a geographically and racially diverse sample of Medicare enrollees with confirmed MM. Using extant selection criteria to study eligible MM patients, we identified claims with anemia (An) or back pain (BP) codes, conditions related to MM. We estimated the period of time between first claim for An or BP and confirmed MM diagnosis. We defined delay as ≥98 days (the median) between initial An or BP claim and MM diagnosis, and estimated logit models to predict sociodemographic and clinical factors associated with delay. We also estimated logit models to predict the likelihood of renal or skeletal complications following MM diagnosis. The study period was one year before, through six months following, diagnosis. Analyses were adjusted for a known 30-day lag time in MM diagnosis dates in SEER. Results: From the analytic sample of 5,185 patients, 3,600 had a diagnosis for An (2,576) and/or BP (2,012) prior to MM diagnosis. Male gender (OR 0.73, 95% CI 0.64–0.84) and northeast region (0.79, 0.65–0.96) decreased the likelihood of delay. Over 60% of patients had ≥ 1 Charlson comorbidity; higher Charlson scores and the presence of both An and BP increased likelihood of delay, but were strongly correlated, and an interaction term with these variables in the model was significant. Of the 5,112 patients with no history of renal or skeletal complications, 1,742 (34%) experienced a complication within six months after MM diagnosis. After adjustment for gender, age, race, and subsequent chemotherapy use, patients with: higher Charlson scores (1.17, 1.03–1.33); initial diagnosis during an inpatient stay (2.40, 1.92–3.00), and; no UPEP, SPEP, or bone marrow biopsy as part of the MM workup (1.68, 1.48–1.92) were more likely to experience a complication (29% of patients had neither PEP nor biopsies recorded). Delay between An or BP diagnosis and MM was not associated with likelihood of complication (0.96, 0.91–1.01). Conclusions: Despite the presence of two classic signs and symptoms of MM, gender and geography significantly influence diagnosis delays. The surprising finding that both anemia and back pain delay diagnosis is partly explained by increased comorbidity in these patients. These findings highlight the importance of considering MM as part of the routine workup for anemia in elderly patients. The existence of comorbidity in these patients may obscure the clinical presentation, resulting in delayed diagnosis. Underuse of common tests to diagnose myeloma may result in poor outcomes, and could be a focus of quality improvement efforts.

Description: Abstract 1369 Poster Board I-391 Background: Timeliness of diagnosis is a quality of care measure endorsed by the Institute of Medicine. Clinical outcomes for patients with chronic myelogenous leukemia (CML) are better when tyrosine kinase inhibitors, such as imatinib, are initiated in the early stages of disease. However, the patterns of care surrounding the CML diagnosis period, as well as the relationship between diagnosis delay and overall survival in the pre-imatinib era, are unknown. Methods: The Surveillance, Epidemiology and End Results (SEER)-Medicare linked database was used to identify traditional Medicare enrollees diagnosed with CML during 1991 through May 2001 (prior to the FDA approval of imatinib). Both inpatient and outpatient claims were analyzed from one year before, through six months following, the SEER diagnosis date. Signs, symptoms, and diagnostic studies commonly encountered in CML diagnoses were identified by CPT procedure and ICD-9 diagnosis and procedure codes. We calculated the time between the first visit for a sign or symptom and the SEER diagnosis date, and defined this time period as ‘diagnostic delay’ if it met or exceeded the median number of days for the sample. An accelerated failure time model examined variables associated with diagnostic delay. Overall survival was examined using a Cox proportional hazards model. Analyses were adjusted to account for a possible lag time in SEER cancer diagnosis dates, as well as year of diagnosis. Results: We studied 768 patients who met eligibility criteria. The most frequent signs and symptoms prior to CML diagnosis were infection (29.4%), anemia (22.4%), leukocytosis (13.4%) and fatigue (11.9%). The median time between any sign or symptom and CML diagnosis date in SEER was 90 days (interquartile range = 270). The median survival time was 3.5 years. The time between sign or symptom and CML diagnosis was increased for patients with at least one comorbidity (β=0.83, p 〈 .001), and for those diagnosed at age 75 or greater (β=0.30, p 〈 .05). Males had shortened times to diagnosis (β=-0.41, p 〈 .01). Diagnostic delay was not a significant predictor of overall survival (HR = 1.04, 95% CI = 0.88-1.23). Conclusions: The most common signs and symptoms older patients experience prior to CML diagnosis are nonspecific, which may impair diagnostic efforts. Prior to the approval and general availability of imatinib, differences in timeliness of diagnosis were observed by age, gender, and presence of comorbidities. Examination of patient-provider interactions stratified by these variables may aid efforts to standardize the diagnostic process, although diagnostic delay was not significantly associated with overall survival in the pre-imatinib era. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 3830 Background: Although the primary care physician (PCP) is often the first point of contact for patients with suspected hematologic malignancy, little is known about hematologic referrals from primary care, including their frequency, the factors that affect choice of specialist, and the quality of information exchanged. Methods: In April 2010, we administered a 34-item questionnaire to a random sample of 190 physicians in the state of Massachusetts identified as PCPs (family practice, general practice, or internal medicine) in the American Medical Association's physician file. PCPs were given the opportunity to complete the survey via post or Internet. An additional mailing was sent to non-respondents, followed by at least two attempts at telephone contact. Physicians were asked for the approximate number of patients seen in the past year with suspected hematologic malignancy, the frequency of formal specialty referral, and informal “curbside” referral. PCPs were also queried about the factors that influence their choice of specialist, and about the information exchange with the specialist; these measures were then analyzed by self-reported PCP characteristics using chi-square statistics. Results: As of August, 2010, 118 physicians had responded (response rate = 62.1%). 67.8% identified themselves as internists, and 61.9% were male. The median reported patient panel size during the prior 12 months was 1800; median percentage of patients ≥ 65 years was 30.0%; median percentage of patients in managed care was 55.0%; and median year of graduation from residency, 1996. PCPs were evenly distributed with respect to academic affiliation (from no affiliation to full-time faculty). The median number (IQR) of patients in the prior 12 months who were suspected of having hematologic malignancy was 5 (3, 10). Among suspected hematologic malignancies, the median number formally referred to a specialist (hematologist or surgeon) was 5 (3, 10), and the median number who received informal “curbside” consult was 0 (0, 0.5). Respondents rated the importance of several factors in their choice of specialist (1 = not important at all to 5 = extremely important). Those factors rated ≥ 3 included reputation of specialist/facility (94.9%), patient's preference for site of care (92.4%), distance of site from patient's home (89.8%), specialist's affiliation with a cancer center (88.1%), practice's affiliation with specialist (82.2%), personal relationship with specialist (79.7%), patient's ability to pay (67.0%), and availability of clinical trials at the referral site (63.6%). The following table summarizes responses to questions about flow of referral information and follow-up: Conclusions: Consultation for suspected hematologic malignancy from PCPs is relatively infrequent, tends to manifest through formal referral as opposed to informal discussion, and is most often affected by specialist reputation and patient preference for site of care. Only about half of our respondents reported providing the specialist with a referral letter or email, which may result in poor quality of referral information. Alternately, a high number reported giving a copy of abnormal test results to their patients to bring to the specialist, which may ameliorate this issue and reflect an ongoing evolution in the patient/provider partnership. Moreover, fairly often, patients have not been to see the specialist upon follow-up with their PCP. This finding seems to reflect patient cancellations rather than a failure in physician systems, suggesting that increases in patient education and personalized follow-up may be the best approach to ensure completion of timely hematologic referrals. Disclosures: No relevant conflicts of interest to declare.

Description: Introduction: Venous thromboembolism (VTE), defined as deep vein thrombosis (DVT), pulmonary embolism (PE), or both, represents a major cause of morbidity and mortality in patients with cancer. VTE is the second leading cause of death in patients with cancer, after cancer itself, in the United States. Previous studies have suggested differences by race in the occurrence of VTE among cancer patients. The purpose of this study was to investigate clinical differences in black and white patients with VTE and cancer. Methods: We conducted an analysis of a CDC/Duke VTE surveillance project at the three hospitals in Durham County, North Carolina (Duke University Hospital, Duke Regional Hospital and the Durham VA Medical Center) from April 2012 through March 2014. A combination of electronic and manual review methods were used to identify unique Durham County residents with new diagnoses of objectively confirmed VTE. Data abstracted included demographics, risk factors including cancer, clinical data, treatment, and outcomes. Results: A total of 1028 patients with a new VTE were identified during the surveillance period. Twenty-seven patients who were not black or white (e.g., race not listed; Asian; etc), and 41 with VTE affecting areas other than PE or limb DVT (e.g., cerebral sinus venous thrombosis) were excluded from this analysis. Of the remaining 960 patients, slightly more than half were female (497/960=51.8%), more than half were black (508/960=52.9%), almost a third were obese (337/960 = 35.1%), and median age was 59 years old. At the time of their VTE diagnosis, 184 patients with VTE (19.2%) had active cancer, defined as metastatic or diagnosed within the previous 6 months. The proportion of VTE associated with cancer varied by race. Among the 508 black patients with VTE, 111 (21.9%) had active cancer; in comparison, among the 452 white patients with VTE, 73 (16.1%) had active cancer (p-value=0.025). Black patients with VTE and cancer were older, had a lower body mass index (BMI), and were less likely to have sustained a prior VTE compared to black patients with VTE who did not have cancer (Table 1). Similarly, white patients with VTE and cancer had a lower BMI than white patients without cancer (Table 1). However, in contrast to the findings for black patients, white patients with VTE and cancer were not significantly older and did not show differences in having a prior VTE than white patients with VTE who did not have cancer. Additionally, white patients with VTE and cancer were much more likely to have sustained a PE, with or without DVT, and less likely to have sustained a DVT alone, than white patients with VTE who did not have cancer (Table 1). Black and white patients with both VTE and cancer, were similar in several aspects; however, white patients were less likely to have sustained a DVT alone and more likely to have sustained a PE, with or without DVT, compared to black patients. The types of cancer most frequently encountered in black patients with VTE were gastrointestinal (24.3%), genitourinary (23.4%), and lung (18.9%), followed by breast (8.1%), gynecologic (9.0%) and hematologic malignancies (9.9%). The types of cancer most frequently encountered in white patients with VTE were lung (27.4%), breast (16.4%), and gastrointestinal (13.7%), followed by genitourinary (9.6%), gynecologic (8.2%) and hematologic malignancies (6.8%). Black and white patients with VTE and cancer were treated similarly to black and white patients with VTE who did not have cancer, with most receiving anticoagulant therapy and fewer than 10% receiving an IVC filter (Table 1). Enoxaparin was used most frequently, followed by warfarin. Conclusions: There are several notable demographic and clinical differences between patients with VTE with and without cancer. While differences were observed for both black and white patients, several factors that were variable according to cancer status were unique to either black patients or white patients. One notable difference between black and white patients with both VTE and cancer was a lower proportion of DVT only and a higher proportion of PE, with or without DVT, in white patients. Disclosures Ortel: Instrumentation Laboratories: Consultancy.

Description: Abstract 2084 BACKGROUND: Although the primary care physician (PCP) is often the first provider to diagnose anemia, little is known about the anemia workup in current clinical practice. Knowledge of current practices can inform efforts to improve anemia management in older adults, which has been recognized as a public health crisis by a combined ASH/National Institute of Aging blue ribbon panel. METHODS: From April to August 2010, we administered a 34-item questionnaire to a random sample of 190 Massachusetts physicians identified as PCPs (family practice, general practice, or internal medicine) in the American Medical Association's physician file. PCPs were given a vignette about a hypothetical patient asking “If you were to see a previously healthy patient during a routine physical with mild anemia (Hg 80% of normal) and no other symptoms, which of the following would you do?” PCPs were given 13 choices, but could also write in answers. In the next section, they were told “The patient with mild anemia presents two weeks later. The anemia is unchanged, but the patient has one new sign/symptom in the following list. For each of these as an isolated new finding, what would you do next?” and asked which of 11 signs/symptoms would prompt (1) imaging (2) referral to a hematologist (3) further follow-up. More than one choice was allowed. Results were analyzed descriptively, and significant differences in the second workup stage were identified using Wald chi-square statistics obtained from logistic regression models controlling for correlations of individual PCP responses. RESULTS: 134 PCPs responded (70.5%). 62.4% identified as internists; 58.7% were male. PCPs were evenly distributed with respect to level of academic affiliation. The median reported patient panel size during the prior 12 months was 1800; median percentage of patients ≥ 65 years was 30.0%; median percentage of patients in managed care 55.0%; and median year of graduation from residency, 1996. For the first stage of the workup, most PCPs reported they would send iron studies (93.2%), a differential (85.7%), and B12/folate (85.0%). Fewer would obtain a stool guaiac (69.2%), reticulocyte count (66.2%), or a serum protein electrophoresis (SPEP; 17.3%). At this first stage, 30.8% reported they would require a 2-week follow-up visit, 26.3% a colonoscopy, and 8.3% an EGD. Almost none would refer to a hematologist (3.8%) or obtain imaging (1.5%), and 12.0% wrote in “work-up depends on patient's age.” Reported subsequent actions with persistent anemia and one new sign or symptom were as follows: Among those patients mostly likely to be referred to a hematologist (those with pancytopenia, thrombocytopenia and leukopenia), PCPs reported recommending low levels of 2-week follow-up in addition to the referral (10.6%, 16.7% and 15.6% respectively). CONCLUSIONS: Use of the reticulocyte count, stool guaiac and SPEP were less frequent than might be expected in the first steps of the anemia work-up; in contrast, more than one-quarter of PCPs reported they would obtain a relatively expensive procedure (colonoscopy) as a first step. Signs and symptoms suggesting bone marrow failure most often prompted referral to a hematologist, while those suggesting lymphoma were generally followed by imaging. Interestingly, an insistent family member could influence hematology referral in the setting of persistent anemia, even more so than night sweats, leukocytosis, or weight loss. These data suggest that several lower-cost diagnostic tools may be underutilized in the PCP's anemia workup, that the workup varies with associated clinical factors, and that patients and families influence the ultimate decision to refer to a hematologist. Disclosures: No relevant conflicts of interest to declare.

Description: Background: Little is known about the patterns of care related to the diagnosis of chronic lymphocytic leukemia (CLL), including the use of modern diagnostic techniques such as flow cytometry. A population-based analysis of the diagnostic process for CLL patients, including predictors and consequences of diagnostic delay, could fuel quality improvement efforts. Methods: The SEER-Medicare linked database for the years 1991–2003 was used to identify traditional Medicare enrollees diagnosed with CLL. Both inpatient and outpatient claims were analyzed from one year before, through six months following, the SEER diagnosis date. Signs, symptoms, and diagnostic studies commonly encountered in CLL diagnoses were identified by ICD-9 diagnosis and CPT procedure codes. Using the dates on claims, we calculated the time between the first visit for a sign or symptom and the SEER diagnosis date. Diagnostic delay was considered present if this time period met or exceeded the median number of days for the sample. Logistic regression models were used to estimate the likelihood of receipt of flow cytometry and of diagnostic delay, using clinical and sociodemographic predictor variables. Overall survival was examined using a Cox proportional hazards model. Analyses were adjusted to account for a known lag time in SEER cancer diagnosis dates. Results: We studied 5,086 patients who met eligibility criteria. Of those, 2,282 (48.9%) had a claim for flow cytometry during the study period, and 1,965 (38.6%) were performed within 30 days of the SEER diagnosis date. The most frequent signs and symptoms prior to diagnosis were infection (32.2%), lymphocytosis, (28.7%), and anemia (23.9%). The median survival time was 9.9 years. The median time between sign or symptom and CLL diagnosis date in SEER (defined as diagnostic delay) was 63 days (interquartile range = 251). Significant predictors of diagnostic delay included age of 75 or higher (OR=1.45, 95% CI = 1.27 to 1.65), female gender (OR = 1.22, 95% CI = 1.07 to 1.39), urban resident (OR = 1.46, 95% CI = 1.19 to 1.79), one or more comorbidities, as measured by the Charlson Comorbidity Index (OR = 2.83, 95% CI = 2.45 to 3.28), and care in a teaching hospital in the year preceding diagnosis (OR = 1.20, 95% CI = 1.05 to 1.38). Significant predictors of receipt of flow cytometry were age below 75 (OR = 1.46, 95% CI = 1.30 to 1.66), urban residence (OR = 1.27, 95% CI = 1.05 to 1.53), northeast residence (OR = 2.01, 95% CI = 1.69 to 2.39), southern residence (OR = 1.51, 95% CI = 1.22 to 1.89) and increasing number of pre-diagnosis signs or symptoms (OR = 1.15, 95% CI = 1.08 to 1.22). In multivariate models, diagnostic delay was not a significant predictor of overall survival (HR = 1.10, 95% CI = 0.98–1.25). Conclusions: In this large national cohort of older adults, age and gender both significantly impact diagnostic delay for CLL, raising a concern for sociodemographic differences in clinicians’ responses to signs and symptoms of hematologic malignancy. In addition, our analysis suggests that the presence of comorbidities may lead clinicians to overlook malignancy as an explanation for hematologic anomalies. Finally, initial use of flow cytometry varies significantly by geography and population density, which may reflect knowledge gaps in recommended diagnostic studies or lack of access to hematopathology services.