Patterns of Care Among Real-World Patients with Metastatic Neuroendocrine Tumors.

BACKGROUND: Although recent pivotal trials (PROMID, CLARINET) have established somatostatin analogs (SSAs) as first-line agents for neuroendocrine tumors (NETs), their use in clinical practice is largely unknown. We aimed to understand real-world management and treatment of gastroenteropancreatic (GEP) NETs. MATERIALS AND METHODS: Patients with metastatic GEP-NETs treated with SSAs, lanreotide depot or octreotide long-acting release (LAR), between January 1, 2015, and December 31, 2015, were identified from a U.S. claims database supplemented with chart review for a subset of patients. Descriptive statistics summarized patients' demographics, clinical characteristics, treatment patterns, and healthcare resource use. Univariate and multivariate comparisons were made across SSA groups. RESULTS: Among 548 patients treated with an SSA for metastatic GEP-NET (lanreotide = 108; octreotide = 440), demographic and clinical characteristics were similar across groups, except more patients with pancreatic NETs were treated with lanreotide (38.7% vs. 6.3%, p < .01). More octreotide patients had a diagnosis of carcinoid syndrome compared with lanreotide patients (19.8% vs. 11.1%, p = .02). Approximately 1.1% of patients received lanreotide (>120 mg every 4 weeks [Q4W]) at a dose above label compared with 12.7% of octreotide patients (>30 mg Q4W; p < .01). At 1.5 years after SSA initiation, 85.7% (95% confidence interval, 74.3%-92.3%) were still on index SSA as reported by the physician. Variances between chart review and claims data were significant. CONCLUSION: SSAs were common in first-line systemic intervention, but dose escalations and dosing deviations outside of label were noted. Variances between claims and chart review warrant additional research to compare methodologies. With an increasing focus on value-based care in oncology, it is critical to understand the use of, and outcomes with, these agents in community practices. IMPLICATIONS FOR PRACTICE: The aim of this study was to enhance understanding of real-world management and treatment of metastatic neuroendocrine tumors (NETs), with particular focus on systemic therapy with a somatostatin analog (SSA). As per published guidelines, SSAs are common in first-line systemic intervention, but dose escalations and dosing deviations outside of the label are noted for symptom control. Nevertheless, oncologists must weigh the implications of the use of above-label dosing of SSAs to manage and treat patients with metastatic NET within a value-based care framework.

Relationship of fluconazole prophylaxis with fungal microbiology in hospitalized intra-abdominal surgery patients: a descriptive cohort study.

INTRODUCTION: Historically, Candida albicans has represented the most common cause of candidemia. However, the proportion of bloodstream infections due to non-albicans Candida species has increased. Because of the risk for candidemia in intra-abdominal surgical patients, some experts advocate the use of fluconazole prophylaxis. The impact of this practice on the distribution of Candida species isolated in breakthrough fungal infections in this population is unknown. We examined the association of fluconazole prophylaxis with the distribution of Candida species in intra-abdominal surgery patients. METHODS: We retrospectively identified cases with a positive blood culture (BCx) for Candida among hospitalized adult intra-abdominal surgery patients between July 2005 and October 2012. Distribution of Candida species isolated represented our primary endpoint. Qualifying surgical cases were determined based on a review of discharge International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. Patients receiving low-dose fluconazole prior to the positive BCx with a known indication for prophylaxis including neutropenia, ICU exposure or history of organ transplantation were classified as prophylaxis. Appropriateness of fungal treatment was determined by the timing and selection of antifungal agent based on fungal isolate. RESULTS: Among 10,839 intra-abdominal surgery patients, 227 had candidemia. The most common Candida species isolated was C. albicans (n = 90, 39.6%) followed by C. glabrata (n = 81, 35.7%) and C. parapsilosis (n = 38, 16.7%). Non-albicans Candida accounted for 57.7% of isolates among the 194 non-prophylaxis patients and 75.8% among the 33 prophylaxis patients (P = 0.001). C. glabrata, the most common non-C. albicans species, was more prevalent than C. albicans in persons given prophylaxis, but not in those without prophylaxis. A total of 63% of those with candidemia were treated inappropriately based on the timing and selection of antifungal administration. CONCLUSIONS: Selection pressure from fluconazole prophylaxis in at-risk surgical patients may be associated with a drift toward fluconazole-resistant species in subsequent candidemia. Tools are needed to guide appropriate treatment through the prompt recognition and characterization of candidemia.

Lenvatinib and Subsequent Therapy for Radioactive Iodine-Refractory Differentiated Thyroid Cancer: A Real-World Study of Clinical Effectiveness in the United States.

INTRODUCTION: Lenvatinib has become the most commonly prescribed first-line (1L) agent for the treatment of radioactive iodine-refractory differentiated thyroid cancer (RAI-r DTC) since its approval in 2015. With no real-world studies describing clinical outcomes of 1L lenvatinib and subsequent therapy, the current study aimed to assess treatment sequencing and related clinical outcomes in patients treated with 1L lenvatinib in the USA METHODS: We conducted a multisite, retrospective chart review of US patients with a diagnosis of RAI-r DTC who had initiated 1L therapy with lenvatinib from January 1, 2016 through May 31, 2017 with follow-up through October 17, 2018. Physicians completed electronic case report forms for two patient cohorts: patients still receiving 1L lenvatinib (cohort 1) and those who had initiated second-line (2L) therapy prior to data cutoff (cohort 2). Real-world objective response rate (ORR) was assessed for both cohorts. Progression-free survival (PFS) and overall survival (OS) were assessed for cohort 2. RESULTS: A total of 252 patients met the study criteria with 71 in cohort 1 and 181 in cohort 2. Patients were predominantly female, had papillary DTC, and had lung metastases. The ORR was 64.8% for cohort 1 and 53.6% for cohort 2. In cohort 2, median PFS from 1L lenvatinib initiation was 14.0 months (95% CI 12.7-15.0). Second-line treatments included sorafenib (49.7%), cabozantinib (19.3%), and other targeted/chemotherapy/immuno-oncology agents. The ORR in 2L therapy was 15.5%. For cohort 2, the 12-, 18-, and 24-month OS from initiation of 1L lenvatinib was 92.8%, 81.5%, and 66.9%, respectively. CONCLUSIONS: In this first real-world examination of clinical effectiveness of 1L lenvatinib and subsequent therapy among patients in the US, the results demonstrated that treatment with 1L lenvatinib followed by another 2L therapy may deliver a clinical benefit, thus allowing a number of potential 2L options following 1L lenvatinib for patients with RAI-r DTC.

Hospitals' compliance with prophylaxis guidelines for venous thromboembolism.

PURPOSE: A study was conducted to evaluate compliance with the Sixth American College of Chest Physicians (ACCP) Consensus Conference on Antithrombotic Therapy guidelines for the prevention of venous thromboembolism (VTE) in hospitals. METHODS: Using the HealthFacts database, hospitalized patients, age 40 years or more, with medical conditions at risk for VTE (surgical, trauma, and acute spinal injury patients) were identified. Hospital admissions on or after January 1, 2001, and concluded by March 31, 2005, were included if they met any of the following conditions as defined in the ACCP Consensus Conference on Antithrombotic Therapy guidelines: patients at risk of VTE medical conditions, major orthopedic surgery, general surgery, gynecological surgery, urologic surgery, trauma, neurosurgery, and acute spinal cord injury. Hospitalizations were identified using the International Classification of Diseases, 9th Revision, Clinical Modification codes. The primary objective was to examine whether patients received one of the indicated anticoagulants at the proper dosage and during the relevant hospital days as determined in the ACCP guidelines. Rates of compliance were assessed, and the reasons for guideline noncompliance were also determined. RESULTS: The overall compliance rate with ACCP guidelines was 13.3% (ranging from 2.8% for neurosurgery to 52.4% for orthopedic surgery) in the 123,304 hospital admissions that were reviewed. Only 15.3% of patients with at-risk medical conditions received prophylaxis in accordance with ACCP guidelines. Potential reasons for guideline noncompliance among selected conditions included the omission of prophylaxis, inadequate prophylaxis duration, and the wrong type of anticoagulant. CONCLUSION: A retrospective study found low rates of compliance with guidelines for thromboprophylaxis.

Mortality differences among organisms causing septicemia in hemodialysis patients.

Septicemia is a serious problem in hemodialysis patients because it can lead to life-threatening complications and a persistently elevated risk of death. Most analyses have not examined whether there are differences in mortality risk among the organisms that cause these episodes of septicemia. This study was a retrospective cohort analysis of first septicemia hospitalizations during the first year of hemodialysis. Time to death (both in-hospital and within 12 weeks post-discharge) was compared among the different septicemia-causing organisms based on discharge diagnoses in Medicare billing data from 1996 to 2001. The effect of various complications on mortality risk was also evaluated. There were 22,130 septicemia hospitalizations identified. The most common organism identified was Staphylococcus aureus (27%), with no other organism having an incidence >10%. The overall unadjusted death rate from admission through 12 weeks of follow-up was 34%. During the first hospitalization, the death rate was 14%, and during the 12-week period after the hospitalization it was 20%. In adjusted analyses, S. aureus was associated with a 20% higher risk of death both during the in-hospital period and the 12-week post-discharge period, when compared with all other specified organisms. Hospitalizations complicated by meningitis, stroke, or endocarditis were also associated with increased risk of mortality, independent of the organism causing septicemia. Septicemia hospitalizations are associated with a high mortality rate--both during the initial hospitalization and after discharge. Meningitis, stroke, and endocarditis represent particularly serious complications. Overall, septicemia hospitalizations (especially for S. aureus) are serious events, and patients would benefit from better treatment and prevention.

Clinical and economic outcomes of Staphylococcus aureus septicemia in ESRD patients receiving hemodialysis.

BACKGROUND: Serious infections are a common problem in patients with end-stage renal disease (ESRD). The purpose of this study is to identify clinical and economic consequences of hospitalizations for septicemia caused by Staphylococcus aureus in hemodialysis patients with ESRD. METHODS: We conducted a retrospective analysis of data obtained from the US Renal Data System to determine lengths of stay and Medicare paid costs for index hospitalizations and episodes of care for patients with ESRD hospitalized with septicemia caused by S aureus. Factors associated with hospital length of stay and Medicare paid costs were examined in multivariate analysis. RESULTS: A total of 11,572 patient admissions with septicemia caused by S aureus were included; 20.7% of patients developed 1 or more complications. Average length of stay for the index admission was 13.0 days, and 11.8% of patients were readmitted within 12 weeks for care related to S aureus. Average Medicare cost for the index admission was 17,307 dollars. Average episodic cost of care, including the index hospitalization, outpatient visits, and readmissions related to S aureus during the subsequent 12 weeks, was 20,067 dollars. S aureus--related complications were associated with greater episodic costs of care: no complications, 18,476 dollars; one complication, 25,804 dollars (P < 0.05 versus no complications); and 2 or more complications, 32,102 dollars (P < 0.05 versus no complications). In multivariate analysis, complications resulted in increased mean lengths of stay of 4 to 7 days, and complications were among the strongest predictors of total episodic costs. CONCLUSION: Patients with septicemia caused by S aureus had costly and lengthy hospitalizations, which frequently were associated with clinically and economically important complications, including hospital readmissions.

Prevalence and outcomes of anemia in rheumatoid arthritis: a systematic review of the literature.

Anemia is a common comorbidity in individuals with rheumatoid arthritis (RA). In fact, anemia of the type characterized by low serum iron concentrations in conjunction with adequate iron stores is frequently associated with RA and has served as a model for anemia of chronic disease. A systematic search of the scientific literature published since January 1966 identified 19 articles that reported findings on either the prevalence of anemia in patients with RA or outcomes for patients with anemia and RA. Ten articles addressed the prevalence of anemia in patients with RA. Estimates of the prevalence of mild anemia ranged between 33% and 60%; however, the 2 studies that examined demographics in patients with RA did not identify subpopulations at particular risk for anemia. Twelve articles assessed the impact of the resolution of anemia on symptoms and quality of life (QOL) in patients with RA. For many of the parameters assessed-including swollen, painful, and tender joints, pain, muscle strength, and energy levels-a positive correlation was observed between improvement of symptoms and the resolution of anemia. In addition, 2 studies reported a significant improvement in QOL scores in patients with RA who experienced a response to treatment for anemia. These results suggest that (1) patients with RA who have anemia are likely to have more severe joint disease and (2) if the anemia is successfully treated, the joint disease will likely respond to treatment as well. Whether improvements in QOL and/or joint symptoms occur with improvement of anemia, independent of other signs of an overall response to RA therapy, remains to be determined.

Effect of an oral contraceptive containing ethinyl estradiol and drospirenone on premenstrual symptomatology and health-related quality of life.

OBJECTIVE: To evaluate the effect of the oral contraceptive Yasmin (drospirenone, 3 mg, and ethinyl estradiol, 30 micrograms) (Berlex Laboratories, Wayne, New Jersey) on premenstrual symptomatology and health-related quality of life (HRQoL). STUDY DESIGN: Participating health care providers received 11,260 self-administered surveys for distribution to women initiating use of Yasmin. Of these, 1,932 (17.2%) baseline surveys and 1,104 follow-up surveys (57.1%) were returned, with 858 (44.4%) of the returns evaluated as suitable for analysis. RESULTS: Premenstrual symptomatology, as measured with the negative affect and water retention domains of the Moos Menstrual Distress Questionnaire (MDQ), significantly improved from baseline in all phases of the menstrual cycle (P = .000). All individual MDQ items improved significantly in the late luteal phase and during menses (P = .000), and the majority (76.9%) improved significantly in the remainder of the cycle (P < .05). Improvements were also observed in general sense of well-being (P < .05), impairment in usual activities due to premenstrual symptomatology (P < .05) and Mental Component Summary scale (P = .000) but not the Physical Component Summary scale of the Short Form-12 generic HRQoL instrument. CONCLUSION: These data support the effectiveness of Yasmin in reducing premenstrual symptomatology and improving HRQoL and general sense of well-being.

Implementation of a pharmacy-based adult vaccine benefit: recommendations for a commercial health plan benefit.

BACKGROUND: Although vaccination rates in children exceed 90% in the United States, adults are vaccinated at far lower rates. In order to address this issue, additional community immunizers are needed, and pharmacists are in an ideal position to fill this void. OBJECTIVES: To explore issues and barriers related to implementation of a pharmacy-based adult vaccine benefit and develop recommendations supporting a pathway for benefit expansion. METHODS: A literature review on the current environment surrounding pharmacy-based adult vaccinations and structured interviews were conducted to inform an expert panel meeting using a modified Delphi process (pre/post survey). The goal was to develop recommendations on how to improve access to adult vaccines. RESULTS: Findings suggest employers play a key role in requesting changes in benefit design to include pharmacy-based vaccinations. However, the lack of consistent communication between pharmacists and primary care providers remains a significant barrier. CONCLUSIONS: Pharmacy-based access to vaccinations improves patient access and benefits individuals and employers. In order to take advantage of this opportunity, pharmacists must be viewed within the broader context of preventative care, including pharmacy-based vaccinations.

Association of blood glucose levels with in-hospital mortality and 30-day readmission in patients undergoing invasive cardiovascular surgery.

OBJECTIVE: This study aimed to evaluate the association of mean and maximum blood glucose (BG) levels with in-hospital mortality and 30-day hospital readmission among patients in the intensive care unit (ICU) undergoing invasive cardiovascular (CV) surgery. RESEARCH DESIGN AND METHODS: The retrospective database analysis consisted of data from 3132 patients from 17 hospitals who underwent an invasive CV surgery during 1/2000-12/2006. Patients with hyperglycemia were identified based on serum BG levels recorded from 12 hours prior to and 24 hours after ICU admission. Separate logistic regression models were used to examine the association of mean and maximum BG levels to in-hospital mortality and 30-day readmission, adjusting for patient demographics, comorbidities and laboratory values. RESULTS: The adjusted odds ratio (OR) for in-hospital mortality was 1.07 (95% CI: 1.01-1.12; p < .001) for every 0.56-mmol/L increase in mean BG, and OR = 1.06 (95% CI: 1.03-1.08, p < .001) for every 0.56-mmol/L increase in maximum BG. Mean BG was not associated with 30-day readmission while maximum BG had a borderline association: OR = 1.02 (95% CI: 1.00-1.03, p = .06). LIMITATION: The results are not generalizable to all cardiovascular surgical patients since only those undergoing invasive procedures were included in the study. CONCLUSIONS: Higher mean and maximum BG levels were associated with increased risk of in-hospital mortality but not with 30-day readmission. Further research is needed to identify optimal BG targets and the effects of avoiding extreme hyperglycemia on patient outcomes.

Are atrial fibrillation patients receiving warfarin in accordance with stroke risk?

BACKGROUND: Clinical guidelines for the management of atrial fibrillation and atrial flutter provide recommendations for anticoagulation based on patients' overall risk of stroke. To determine the real-world compliance of physicians with these recommendations, we conducted a retrospective cohort study examining the utilization of warfarin in atrial fibrillation/flutter patients by stroke risk level. METHODS: Patients with a qualifying atrial fibrillation/flutter diagnosis during > or =18 months' continuous enrollment between January 2003 and September 2007, and with > or =6 months' eligibility after the first atrial fibrillation/flutter diagnosis, were identified from the US MarketScan database (Thomson Reuters, New York, NY). Warfarin use within 30 days of the first diagnosis was assessed according to stroke risk, estimated using the Congestive heart failure, Hypertension, Age >75 years, Diabetes, Stroke (CHADS(2)) score. RESULTS: Of 171,393 patients included in the analysis, 20.0% had a CHADS(2) score of 0 (low risk), 61.6% a score of 1-2 (moderate risk), and 18.4% a score of 3-6 (high risk). Warfarin, recommended for high stroke-risk patients, was given to only 42.1% of those with a CHADS(2) score of 3-6. A similar percentage of patients with moderate (43.5%) or low stroke risk (40.1%) received warfarin. Only 29.6% of high-risk, 33.3% of moderate-risk, and 34.1% of low-risk patients who were started on warfarin received uninterrupted therapy for 6 months following their initial prescription. CONCLUSIONS: These data suggest that guideline recommendations that anticoagulation should be provided in accordance with stroke risk in atrial fibrillation patients are not routinely followed in clinical practice. The causes and clinical implications of under-utilization of anticoagulation in atrial fibrillation patients with high stroke risk warrant further study.

Pattern of clopidogrel use in hospitalized patients receiving percutaneous coronary interventions.

PURPOSE: The pattern of clopidogrel loading in patients who had undergone percutaneous coronary intervention (PCI) was studied in a retrospective analysis of clinical records. METHODS: A database of deidentified electronic medical records from hospitals and hospital-affiliated outpatient facilities throughout the United States was analyzed for PCI patients with or without a diagnosis of acute coronary syndrome (ACS) who received clopidogrel loading doses of > or =300 mg between 48 hours before and 6 hours after PCI. A high dose was defined as > or =600 mg, and pretreatment was defined as more than 6 hours before PCI for 300-599 mg and 2 or more hours before PCI for > or =600 mg. RESULTS: Among 6253 PCI patients who met the criteria, there were 2331 with a diagnosis of ACS (ACS-PCI) and 3922 without an ACS diagnosis (elective PCI). Of the ACS-PCI patients, 1359 had ST-segment elevation myocardial infarction (STEMI) and 972 had unstable angina (UA) or non-ST-segment elevation myocardial infarction (NSTEMI). A majority of ACS-PCI patients (57%) received a > or =600-mg loading dose, 34% received a 300-mg loading dose, and the rest received a loading dose between 300 and 600 mg. Loading consisted of a single bolus in 75% of patients, two doses in 21.5%, and three or more doses in 3.1%. The first dose was during or after PCI in 56% of the UA/NSTEMI group and in 71% of both the elective PCI and STEMI groups. Among the UA/NSTEMI group, only 33% met criteria for pretreatment. CONCLUSION: Reported practice patterns of clopidogrel administration before PCI for UA/NSTEMI were not consistent with evidence generated from published clinical trials and guidelines. Recommended pre-treatment with clopidogrel was frequently not practiced.

Development and validation of a case ascertainment tool for ankylosing spondylitis.

OBJECTIVE: Ankylosing spondylitis (AS) diagnosis is often delayed. The availability of effective biologic agents for treating AS has increased the importance of early diagnosis. We tested questions derived from a comprehensive literature review and an advisory board in a case-control study designed to identify patients with AS from among patients with chronic back pain (CBP). METHODS: Question items were cognitively tested among patients with AS, and then in case-control studies for validation and creation of a scoring algorithm and question item reduction. AS cases were recruited from a known database, and CBP subjects (controls) were recruited from clinics, employers, and from the SpineUniverse Web site. We used individual question items in a multivariate framework to discriminate between people with and without AS. RESULTS: Forty-three questions yielded 24 items for analyses; 12 of these were entered into a multivariate regression model. Individual items yielded odds ratios ranging from 0.07 to 30.31. Question items with a significant positive relationship to AS included male sex, neck or hip pain/stiffness, longer pain duration, decreased pain/stiffness with daily physical activity, pain relief within 48 hours of nonsteroidal antiinflammatory drugs, and diagnosis of iritis. The tool demonstrated a sensitivity of 67.4 and a specificity of 94.6. The tool was developed from clinically and radiologically diagnosed AS cases and therefore is designed to distinguish AS cases among CBP subjects. In addition, approximately 54% of the AS cases in the study were treated with biologic agents, which may impact questionnaire responses. CONCLUSION: This tool can identify undiagnosed patients with AS and, potentially, those at an earlier stage in their disease course.

Septicemia in patients with ESRD is associated with decreased hematocrit and increased use of erythropoietin.

Septicemia, a common complication in chronic dialysis patients, may be an important factor in erythropoietin (EPO) hyporesponsiveness, because it is a form of inflammation. The quantitative impact of septicemia on EPO requirements has not been studied. The purpose of this study was to analyze patterns of EPO use and levels of anemia among patients who had ESRD and were hospitalized with septicemia. Using United States Renal Data System data, septicemia admissions were identified in patients with first ESRD service from 1996 to 2001. Mean EPO dosage and hematocrit (Hct) level were analyzed from 2 mo before until 3 mo after admission and compared with patients who were hospitalized with acute myocardial infarction (AMI) and patients with no hospitalizations. A total of 4640 hospitalized patients were included in the analysis: 3975 for septicemia and 665 for AMI. In both groups, mean Hct declined significantly in the month of admission and increased in the second month after admission. At all time points, both groups had significantly lower Hct levels compared with the nonhospitalized group. Mean EPO dosage increased, most rapidly in the month after admission. EPO use was highest in the septicemia group. Hospitalization with septicemia is associated with worsening anemia and increasing EPO use. This also was observed for patients who were hospitalized with AMI, suggesting that acute intercurrent illness plays an important role in EPO hyporesponsiveness. Strategies to prevent septicemia are important not only to decrease clinical morbidity but also to conserve EPO usage and thus contain the costs of care for this complex patient population.

Development and validation of a grading system for the quality of cost-effectiveness studies.

PURPOSE: To provide a practical quantitative tool for appraising the quality of cost-effectiveness (CE) studies. METHODS: A committee comprising [corrected] of health economists selected a set of criteria for the instrument from an item pool. Data collected with a conjoint analysis survey on 120 international health economists were used to estimate weights for each criterion with a random effects regression model. To validate the grading system, a survey was sent to 60 individuals with health economics expertise. Participants first rated the quality of three CE studies on a visual analogue scale, and then evaluated each study using the grading system. Spearman rho and Wilcoxon tests were used to detect convergent validity and analysis of covariance (ANCOVA) for discriminant validity. Agreement between the global rating by experts and the grading system was also examined. RESULTS: Sixteen criteria were selected. Their coefficient estimates ranged from 1.2 to 8.9, with a sum of 93.5 on a 100-point scale. The only insignificant criterion was "use of subgroup analyses." Both convergent validity and discriminant validity of the grading system were shown by the results of the Spearman rho (correlation coefficient = 0.78, P < 0.0001), Wilcoxon test (P = 0.53), and ANCOVA (F(3,146) = 5.97, p = 0.001). The grading system had good agreement with global rating by experts. CONCLUSIONS: The instrument appears to be simple, internally consistent, and valid for measuring the perceived quality of CE studies. Applicability for use in clinical and resource allocation decision-making deserves further study.