Prophylaxis of febrile neutropenia with colony-stimulating factors: the first 25 years.

Filgrastim prophylaxis, both primary and secondary, was rapidly incorporated into clinical practice in the 1990s. When pegfilgrastim became available in 2002, it quickly replaced filgrastim as the colony-stimulating factor (CSF) of choice for prophylaxis. Use of prophylaxis increased markedly in the first decade of this century and has stabilized during the present decade. Data concerning real-world CSF prophylactic practice patterns are limited but suggest that both primary and secondary prophylaxis are common, and that use is frequently inappropriate according to guidelines. The extent of inappropriate use is controversial, as are issues concerning the cost-effectiveness of prophylaxis versus no prophylaxis and the cost-effectiveness of primary prophylaxis versus secondary prophylaxis. Nevertheless, CSF prophylaxis is firmly established as a valuable adjunct to chemotherapy and will almost certainly continue to be widely used for the foreseeable future. In this article, we chronicle the use and impact of CSF prophylaxis in US patients receiving myelosuppressive chemotherapy for non-myeloid malignancies. We emphasize the interplay of expert opinion, clinical evidence, and economic factors in shaping the use of CSFs in clinical practice over time, and, with the recent introduction of new CSF agents and options, we aim to provide useful clinical and economic information for healthcare decision makers.

Cost-effectiveness of an autoantibody test (EarlyCDT-Lung) as an aid to early diagnosis of lung cancer in patients with incidentally detected pulmonary nodules.

OBJECTIVE: Patients who have incidentally detected pulmonary nodules and an estimated intermediate risk (5-60%) of lung cancer frequently are followed via computed tomography (CT) surveillance to detect nodule growth, despite guidelines for a more aggressive diagnostic strategy. We examined the cost-effectiveness of an autoantibody test (AABT)-Early Cancer Detection Test-Lung (EarlyCDT-LungTM)-as an aid to early diagnosis of lung cancer among such patients. METHODS: We developed a decision-analytic model to evaluate use of the AABT versus CT surveillance alone. In the model, patients with a positive AABT-because they are at substantially enhanced risk of lung cancer-are assumed to go directly to biopsy, resulting in diagnosis of lung cancer in earlier stages than under current guidelines (a beneficial stage shift). Patients with a negative AABT, and those scheduled for CT surveillance alone, are assumed to have periodic CT screenings to detect rapid growth and thus to have their lung cancers diagnosed-on average-at more advanced stages. RESULTS: Among 1,000 patients who have incidentally detected nodules 8-30 mm, have an intermediate-risk of lung cancer, and are evaluated by CT surveillance alone, 95 (9.5%) are assumed to have lung cancer (local, 73.6%; regional, 22.0%; distant, 4.4%). With use of the AABT set at a sensitivity/specificity of 41%/93% (stage shift = 10.8%), although expected costs would be higher by $949,442 ($949 per person), life years would be higher by 53 (0.05 per person), resulting in a cost per life-year gained of $18,029 and a cost per quality-adjusted life year (QALY) gained of $24,330. With use of the AABT set at a sensitivity/specificity of 28%/98% (stage shift = 7.4%), corresponding cost-effectiveness ratios would be $18,454 and $24,833. CONCLUSIONS: Under our base-case assumptions, and reasonable variations thereof, using AABT as an aid in the early diagnosis of lung cancer in patients with incidentally detected pulmonary nodules who are estimated to be at intermediate risk of lung cancer and are scheduled for CT surveillance alone is likely to be a cost-effective use of healthcare resources.

Risk of infection among patients with non-metastatic solid tumors or non-Hodgkin's lymphoma receiving myelosuppressive chemotherapy and antimicrobial prophylaxis in US clinical practice.

Purpose Guidelines generally do not recommend oral antimicrobials for prophylaxis against chemotherapy-related infections in patients with solid tumors. Evidence on antimicrobial prophylaxis use, and associated chemotherapy-related infection risk, in US clinical practice is limited. Methods A retrospective cohort design and data from two US private healthcare claims repositories (2008-2011) were employed. Study population included adults who received myelosuppressive chemotherapy for non-metastatic cancer of the breast, colon/rectum, or lung, or for non-Hodgkin's lymphoma. For each subject, the first chemotherapy course was characterized, and within the first course, each chemotherapy cycle and chemotherapy-related infection episode was identified. Use of prophylaxis with oral antimicrobials and colony-stimulating factors in each cycle also was identified. Results A total of 7116 (22% of all) non-metastatic breast cancer, 1833 (15%) non-metastatic colorectal cancer, 1999 (15%) non-metastatic lung cancer, and 1949 (21%) non-Hodgkin's lymphoma patients received antimicrobial prophylaxis in ≥1 cycle. Mean number of antimicrobial prophylaxis cycles during the course among these patients was typically <2, with little difference across cancers and chemotherapy regimens. Fluoroquinolones were the most commonly received class of antimicrobials, accounting for 20%-50% all antimicrobials administered. Among subjects who received first-cycle antimicrobial prophylaxis, chemotherapy-related infection risk in that cycle ranged from 3% to 6% across cancer types. Among patients who received first-cycle antimicrobial prophylaxis and developed chemotherapy-related infections, 38%-67% required inpatient care. Chemotherapy-related infection risk in subsequent cycles with antimicrobial prophylaxis was comparable. Conclusion The results of this study suggest that use of antimicrobial prophylaxis during myelosuppressive chemotherapy is far from uncommon in clinical practice. The results also suggest that an important minority of cancer chemotherapy patients receiving antimicrobial prophylaxis still develop serious infection requiring hospitalization.

Risk and Consequences of Chemotherapy-Induced Febrile Neutropenia in Patients With Metastatic Solid Tumors.

PURPOSE: Although studies have evaluated the risk and consequences of febrile neutropenia (FN) among patients receiving cancer chemotherapy in US clinical practice, none have focused on a broad group of patients with metastatic disease. METHODS: A retrospective cohort design and health care claims (2006 to 2011) from private health plans covering a geographically diverse US population of > 30 million persons annually were used. The study population included adults who underwent myelosuppressive chemotherapy for metastatic cancer of the breast (MBC), colon/rectum (MCRC), lung (MLC), ovaries (MOC), or prostate (MPC). For each patient, the first chemotherapy course and each cycle therein, along with each episode of FN and the consequences thereof, were identified. RESULTS: The most common regimens, by cancer type, were paclitaxel (18% of 15,318 patients with MBC); oxaliplatin, fluorouracil, and leucovorin (23% of 16,923 patients with MCRC); carboplatin plus paclitaxel (23% of 21,999 patients with MLC); carboplatin plus paclitaxel (49% of 7,433 patients with MOC); and docetaxel (68% of 4,667 patients with MPC). Across cancers, FN occurred in 13.1% to 20.6% of patients during their chemotherapy course, most often required hospitalization (89% to 94%), and most often occurred in the first cycle (23% to 36%). Among hospitalized patients with FN, mean length of stay ranged from 7.0 to 7.5 days, and inpatient mortality ranged from 3.9% to 10.3%; mean FN-related costs during the cycle ranged from $16,291 to $19,456. CONCLUSION: Among patients receiving myelosuppressive chemotherapy for metastatic cancer in US clinical practice, FN is a frequent complication, associated with significant morbidity, mortality, and economic costs, and should be given careful consideration in the treatment of this population.

Risk of febrile neutropenia in patients receiving emerging chemotherapy regimens.

PURPOSE: Considerable evidence exists concerning the risk of febrile neutropenia (FN) associated with well-established, older chemotherapy regimens. Little is known, however, about the risks associated with many regimens that were introduced in the past decade and have become the predominant choice for certain cohorts of patients or are increasingly being used in clinical practice. METHODS: A retrospective cohort design and US healthcare claims data (2006-2011) were employed. Study subjects included adult patients receiving the following: docetaxel + cyclophosphamide (TC), 5-FU + epirubicin + cyclophosphamide (FEC), FEC followed by docetaxel (FEC → D), or docetaxel + carboplatin + trastuzumab (TCH) for non-metastatic breast cancer; TCH for metastatic breast cancer; 5-FU + leucovorin + irinotecan + oxaliplatin (FOLFIRINOX) for metastatic pancreatic cancer; and bendamustine (with rituximab [BR], without rituximab [B-Mono]) for non-Hodgkin's lymphoma (NHL). For each patient, the first qualifying chemotherapy course and each cycle therein were identified, as were the use of supportive care-colony-stimulating factors (CSF) and antimicrobials (AMB)-and unique FN episodes. RESULTS: The crude risk (incidence proportion) of FN during the chemotherapy course ranged from 8.8 (95 % CI 8.3-9.3) to 10.6 % (9.3-12.1) among the breast cancer regimens, was slightly higher for the NHL regimens (BR, 10.5 % [8.9-12.4]; B-Mono, 14.7 % [11.2-18.9]), and was markedly higher for FOLFIRINOX (24.7 % [17.9-33.1]). Most patients developing FN required inpatient care (range, 73-90 %). Use of CSF primary prophylaxis ranged from 17 (B-Mono) to 75 % (FEC → D); use of AMB primary prophylaxis ranged from 6 (FOLFIRINOX) to 13 % (B-Mono). CONCLUSION: The risk of FN among patients receiving selected emerging chemotherapy regimens is considerable, and most cases require inpatient care. Use of CSF and AMB prophylaxis, however, varies substantially across regimens.

Clinical and economic consequences of post-operative infections following major elective surgery in U.S. hospitals.

BACKGROUND: The incidence and consequences of post-operative infections in patients undergoing major elective surgery is not well understood. METHODS: Using a large U.S. healthcare claims database, we identified all patients who underwent major elective surgery between January 1, 2007, and December 31, 2009. For each such patient, date of the first-noted surgery during this period was designated as the index date. Patients who developed infections within 30 d of their index date were matched to those who did not using propensity score matching. We compared hospital readmissions, mortality, and total healthcare cost during the 30-d period following index date between patients who developed post-operative infections versus those who did not. RESULTS: A total of 327,618 patients met all selection criteria. At 30 d following major elective surgery, 10.9% of patients had evidence of post-operative infections, 39% of which occurred during the index admission. In propensity-matched analyses, patients with post-operative infections were about five times as likely to be readmitted to hospital (11.3% vs. 2.1%) and more than twice as likely to die (0.8% vs. 0.3%) in the 30-d period following surgery; their average total healthcare cost was $8,417 higher ($29,229 vs. $20,812) (all comparisons, p<0.01). CONCLUSION: Approximately one in 10 patients undergoing major elective surgery develop post-operative infections by day 30. Post-operative infections are associated with significantly worse clinical outcomes and higher total healthcare cost.

Risk and consequences of chemotherapy-induced neutropenic complications in patients receiving daily filgrastim: the importance of duration of prophylaxis.

BACKGROUND: To examine duration of daily filgrastim prophylaxis, and risk and consequences of chemotherapy-induced neutropenic complications (CINC) requiring inpatient care. METHODS: Using a retrospective cohort design and US healthcare claims data (2001-2010), we identified all cancer patients who initiated ≥1 course of myelosuppressive chemotherapy and received daily filgrastim prophylactically in ≥1 cycle. Cycles with daily filgrastim prophylaxis were pooled for analyses. CINC was identified based on hospital admissions with a diagnosis of neutropenia, fever, or infection; consequences were characterized in terms of hospital mortality, hospital length of stay (LOS), and CINC-related healthcare expenditures. RESULTS: Risk of CINC requiring inpatient care-adjusted for patient characteristics-was 2.4 (95% CI: 1.6-3.4) and 1.9 (1.3-2.8) times higher with 1-3 (N = 8371) and 4-6 (N = 3691) days of filgrastim prophylaxis, respectively, versus ≥7 days (N = 2226). Among subjects who developed CINC, consequences with 1-3 and 4-6 (vs. ≥7) days of filgrastim prophylaxis were: mortality (8.4% [n/N = 10/119] and 4.0% [3/75] vs. 0% [0/34]); LOS (means: 7.4 [N = 243] and 7.1 [N = 99] vs. 6.5 [N = 40]); and expenditures (means: $18,912 [N = 225] and $14,907 [N = 94] vs. $13,165 [N = 39]). CONCLUSIONS: In this retrospective evaluation, shorter courses of daily filgrastim prophylaxis were found to be associated with an increased risk of CINC as well as poorer outcomes among those developing this condition. Because of the limitations inherent in healthcare claims databases specifically and retrospective evaluations generally, additional research addressing these limitations is needed to confirm the findings of this study.

Use of intravenous bisphosphonates in patients with breast, lung, or prostate cancer and metastases to bone: a 15-year study in two large US health systems.

PURPOSE: The purpose of this paper is to document the use of intravenous (IV) bisphosphonates for prevention of skeletal-related events (SREs) in patients with bone metastases (BM) due to breast cancer (BC), lung cancer (LC), or prostate cancer (PC). METHODS: Using data from two large US health systems, we identified all patients aged ≥ 18 years with primary BC, LC, or PC and newly diagnosed BM between 1/1/1995 and 12/31/2009. Starting with the diagnosis of BM, we reviewed medical and administrative records for evidence of receipt of IV bisphosphonates (zoledronic acid or pamidronate) and occurrence of SREs. Initiation of IV bisphosphonates prior to occurrence of an SRE was designated "primary prophylaxis"; use following an SRE was designated "secondary prophylaxis". RESULTS: We identified a total of 1,193 patients with newly diagnosed BM, including 400 with BC, 332 with LC, and 461 with PC. Use of IV bisphosphonates was substantially higher in BC (55.8 % of all patients) than in LC (14.8 %) or PC (20.2 %). Use of IV bisphosphonates was fairly evenly split between primary and secondary prophylaxis in BC (26.3 vs. 29.5 %, respectively) and PC (10.6 vs 9.5 %); in LC, however, primary prophylaxis was much less common than secondary prophylaxis (4.8 vs 9.9 %). CONCLUSIONS: Almost one half of all patients with BM due to BC, and substantially more with LC and PC, do not receive IV bisphosphonates. Among patients receiving such therapy, treatment often is not initiated until after the occurrence of an SRE. Our study suggests that IV bisphosphonates may be substantially underutilized in patients with BM due to these common cancers.

Natural history of skeletal-related events in patients with breast, lung, or prostate cancer and metastases to bone: a 15-year study in two large US health systems.

PURPOSE: To document the risk of skeletal complications in patients with bone metastases from breast cancer (BC), lung cancer (LC), or prostate cancer (PC) in routine clinical practice. METHODS: We used data from two large US health systems to identify patients aged ≥18 years with primary BC, LC, or PC and newly diagnosed bone metastases between January 1, 1995 and December 31, 2009. Beginning with the date of diagnosis of bone metastasis, we estimated the cumulative incidence of skeletal-related events (SREs) (spinal cord compression, pathologic fracture, radiation to bone, bone surgery), based on review of medical records, accounting for death as a competing risk. RESULTS: We identified a total of 621 BC, 477 LC, and 721 PC patients with newly diagnosed bone metastases. SREs were present at diagnosis of bone metastasis in 22.4, 22.4, and 10.0 % of BC, LC, and PC patients, respectively. Relatively few LC or PC patients received intravenous bisphosphonates (14.8 and 20.2 %, respectively); use was higher in patients with BC, however (55.8 %). In BC, cumulative incidence of SREs during follow-up was 38.7 % at 6 months, 45.4 % at 12 months, and 54.2 % at 24 months; in LC, it was 41.0, 45.4, and 47.7 %; and in PC, it was 21.5, 30.4, and 41.9 %. More than one half of patients with bone metastases had evidence of SREs (BC: 62.6 %; LC: 58.7 %; PC: 51.7 %), either at diagnosis of bone metastases or subsequently. CONCLUSIONS: SREs are a frequent complication in patients with solid tumors and bone metastases, and are much more common than previously recognized in women with BC.

Technical evaluation of methods for identifying chemotherapy-induced febrile neutropenia in healthcare claims databases.

BACKGROUND: Healthcare claims databases have been used in several studies to characterize the risk and burden of chemotherapy-induced febrile neutropenia (FN) and effectiveness of colony-stimulating factors against FN. The accuracy of methods previously used to identify FN in such databases has not been formally evaluated. METHODS: Data comprised linked electronic medical records from Geisinger Health System and healthcare claims data from Geisinger Health Plan. Subjects were classified into subgroups based on whether or not they were hospitalized for FN per the presumptive "gold standard" (ANC <1.0×10(9)/L, and body temperature ≥38.3°C or receipt of antibiotics) and claims-based definition (diagnosis codes for neutropenia, fever, and/or infection). Accuracy was evaluated principally based on positive predictive value (PPV) and sensitivity. RESULTS: Among 357 study subjects, 82 (23%) met the gold standard for hospitalized FN. For the claims-based definition including diagnosis codes for neutropenia plus fever in any position (n=28), PPV was 100% and sensitivity was 34% (95% CI: 24-45). For the definition including neutropenia in the primary position (n=54), PPV was 87% (78-95) and sensitivity was 57% (46-68). For the definition including neutropenia in any position (n=71), PPV was 77% (68-87) and sensitivity was 67% (56-77). CONCLUSIONS: Patients hospitalized for chemotherapy-induced FN can be identified in healthcare claims databases--with an acceptable level of mis-classification--using diagnosis codes for neutropenia, or neutropenia plus fever.

Prophylaxis against venous thromboembolism in hospitalized medically ill patients.

BACKGROUND: Many hospitalized medically ill patients are at risk of venous thromboembolism (VTE). Risk factors include prior VTE, older age, immobility, obesity, cardiac or respiratory failure, and cancer (at-risk patients). Although guidelines recommend use of VTE prophylaxis for at-risk patients, many may not receive it. METHODS AND RESULTS: Using a database linking admission records from >150 US hospitals to health insurance claims, we identified people ≥40 years of age, hospitalized from 2003 to 2008. We excluded patients who: (1) were treated for VTE or hospitalized in the previous 30 days; (2) were admitted for traumatic injury or surgery; (3) had hypercoagulability at admission; or (4) received therapeutic dosages of low-molecular weight heparin, unfractionated heparin, or fondaparinux at admission. We examined the use of VTE prophylaxis (both pharmacological and nonpharmacological) on day 1 or 2 in hospital among at-risk patients; predictors of receipt of prophylaxis were examined using multivariate logistic regression. The study population consisted of 49 948 patients, of whom 34 374 (69%) were at risk. Only 18% of at-risk patients received VTE prophylaxis on day 1 or 2 in hospital, typically with low-molecular weight heparin (56% of patients receiving prophylaxis), intermittent pneumatic compression (25%), warfarin (16%), or graduated compression stockings (11%). Use of prophylaxis exceeded 25% only in patients admitted from nursing homes and those with prior VTE. Although there were several significant predictors of receipt of VTE prophylaxis, model discrimination was relatively poor (C-statistic=0.61). CONCLUSION: The majority of at-risk hospitalized medically ill patients do not receive VTE prophylaxis.

Risk and healthcare costs of chemotherapy-induced neutropenic complications in women with metastatic breast cancer.

BACKGROUND: The burden of chemotherapy-induced neutropenic complications (CINC) in women with metastatic breast cancer (MBC) is largely unknown and may differ across cancer populations due to variation in the characteristics of patients, their disease and their treatment. METHODS: This study employed a retrospective cohort design and US healthcare claims data (2003-2009). For each woman in the study database who received myelotoxic chemotherapy for MBC, the first observed course and each cycle within the course were characterized. Risk and healthcare costs of CINC - by care setting - were descriptively analyzed on an overall basis by chemotherapy cycle and chemotherapy regimen. RESULTS: Among 2,620 study subjects, most received chemotherapy with cyclophosphamide/doxorubicin (25%), docetaxel (20%) or paclitaxel (12%). Thirty-one percent of subjects received colony-stimulating factors (CSF) prophylactically in their first chemotherapy cycle and an additional 13% first received CSF prophylaxis after cycle one. CINC developed in 11% of subjects; among these subjects, 88% required inpatient care and 45% experienced CINC in the first cycle of chemotherapy. For CINC requiring inpatient care, costs averaged USD 12,869 (95% CI: USD 12,622-13,116), and for CINC requiring outpatient care only, USD 2,030 (CI: USD 1,925-2,135). CONCLUSION: CINC is a clinically and economically important threat among women with MBC, and should be an important consideration in the treatment of this population.

Incidence of reduced chemotherapy relative dose intensity among women with early stage breast cancer in US clinical practice.

Chemotherapy is widely used to treat early stage breast cancer (ESBC). Reductions and delays in dose administered--e.g., due to advanced age or febrile neutropenia (FN)--are generally believed to increase risk of disease progression and reduce survival. Little is known about incidence of reduced chemotherapy dose intensity among women with ESBC in the current era of US clinical practice. This study employed a retrospective cohort design and electronic medical records from > 65 community oncology/hematology clinics in > 35 states (2004-2010). The study population comprised adult women who received myelosuppressive chemotherapy for ESBC (stages I-IIIA). For each such woman, each unique cycle of chemotherapy within their first observed course was identified. Incidence of chemotherapy dose delays (≥ 7 days for any drug in ≥ 1 cycles), chemotherapy dose reductions (≥ 15% for any drug in ≥ 1 cycles), and low chemotherapy relative dose intensity (RDI <85% over the course) relative to published reference standards were descriptively analyzed for the seven most-frequently planned regimens in the study database. A total of 2,228 women (70% of the subjects who received chemotherapy for ESBC and met other selection criteria) initiated 1 of the 7 most-frequently planned regimens. Mean age of subjects was 54 years and 69% received primary prophylaxis against FN with a colony-stimulating factor. Incidence of dose delays, dose reductions, and low RDI was 31, 24, and 26%, respectively; low RDI typically was due to premature treatment discontinuation. For patients (n = 626) receiving the most common regimen (dose-dense AC-T: doxorubicin/cyclophosphamide, Q2 × 4 cycles, paclitaxel or docetaxel, Q2 × 4 cycles), incidence of dose delays, dose reductions, and low RDI was 42, 29, and 32%, respectively. In the current era of US clinical practice, chemotherapy dose delays and dose reductions are common among women with ESBC receiving frequently used myelosuppressive dose-dense, as well as conventional, chemotherapy regimens.

Comparative effectiveness of filgrastim, pegfilgrastim, and sargramostim as prophylaxis against hospitalization for neutropenic complications in patients with cancer receiving chemotherapy.

BACKGROUND: Comparative effectiveness of filgrastim, pegfilgrastim, and sargramostim in preventing hospitalization for febrile neutropenia (FN) during myelosuppressive chemotherapy has not been well characterized and is an important clinical question in oncology. METHODS: This study used a retrospective cohort design and US healthcare claims data. Source population included patients with solid tumors receiving filgrastim, pegfilgrastim, or sargramostim during their first observed course of chemotherapy between July 2001 and June 2007. For each patient, every unique chemotherapy cycle during the course was identified, along with each cycle in which filgrastim, pegfilgrastim, or sargramostim was administered by the fifth day of the cycle (ie, as prophylaxis). Risks of hospitalization for neutropenic complications (broad definition: admission with a diagnosis of neutropenia, fever, or infection; narrow definition: admission with a diagnosis of neutropenia) and for any reason were examined on a cycle-specific basis during all the cycles in which colony-stimulating factor prophylaxis was administered. Unadjusted and adjusted odds ratios (ORs) for hospitalization were estimated. RESULTS: Risk (unadjusted) of hospitalization for neutropenic complications (narrow definition) was 2.1% for filgrastim prophylaxis (n=8286), 1.1% for pegfilgrastim prophylaxis (n=67,247), and 2.5% for sargramostim prophylaxis (n=1736). Corresponding risks of hospitalization based on the broad definition were 4.0%, 2.6%, and 5.1%. Risks of all-cause hospitalization were 7.9%, 5.3%, and 9.6%, respectively. Adjusted odds of hospitalization were significantly higher for filgrastim [OR (range across the 3 alternative measures of hospitalization): 1.58-1.79; P<0.001] and sargramostim (OR: 1.89-2.68; P<0.001) versus pegfilgrastim. CONCLUSIONS: Risk of hospitalization for neutropenic complications during cancer chemotherapy is lower with pegfilgrastim prophylaxis than with filgrastim or sargramostim prophylaxis.

Patterns of pharmacotherapy and health care utilization and costs prior to total hip or total knee replacement in patients with osteoarthritis.

OBJECTIVE: To examine patterns of pharmacotherapy and health care utilization and costs prior to total knee replacement (TKR) or total hip replacement (THR) in patients with osteoarthritis (OA). METHODS: Using a large US health insurance claims database, we identified all patients with OA who were ages ≥40 years and had undergone TKR or THR between January 1, 2006 and December 31, 2007. Patients with <2 years of complete data prior to TKR or THR were excluded, as were those with evidence of other conditions for which TKR or THR may be performed (e.g., rheumatoid arthritis). We then examined patterns of health care utilization and costs over the 2-year period preceding surgery. RESULTS: A total of 16,527 patients met all study entry criteria. Their mean ± SD age was 56.6 ± 6.1 years, and 56% of them were women. In the 2 years preceding surgery, 55% of patients received prescription nonsteroidal antiinflammatory drugs, 58% received opioids, and 50% received injections of corticosteroids. The numbers of patients receiving these drugs increased steadily during the presurgery period. The mean ± SD total health care costs in the 2 years preceding surgery were $19,466 ± 29,869, of which outpatient care, inpatient care, and pharmacotherapy represented 45%, 20%, and 20%, respectively. Costs increased from $2,094 in the eighth calendar quarter prior to surgery to $3,100 in the final quarter. CONCLUSION: Patients with OA who undergo THR or TKR have relatively high levels of use of pain-related pharmacotherapy and high total health care costs in the 2-year period preceding surgery. Levels of utilization and cost increase as the date of surgery approaches.

Patterns of healthcare utilization and cost in patients with newly diagnosed fibromyalgia.

OBJECTIVES: To compare healthcare utilization and costs in the year preceding and following initial diagnosis of fibromyalgia (FM). METHODS: Using a large US health insurance claims database, we identified all persons with newly diagnosed FM (International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code 729.1) between January 1, 2003, and December 31, 2005 ("FM patients"). Each patient's first-noted claim with a diagnosis of FM was designated the "index date," and all pharmacy, outpatient, and inpatient claims were compiled over the 12-month periods preceding and following this date ("prediagnosis" and "postdiagnosis," respectively). Patients with incomplete pre- or postdiagnosis data were excluded. Healthcare utilization and costs were compared between the 2 periods. RESULTS: A total of 1803 patients met all study inclusion criteria; mean (SD) age was 50.4 (9.4) years; 91% were women. Comorbidities were common, including arthritis (21% of study subjects), back pain (20%), and painful neuropathic disorders (16%). The percentage of study subjects receiving various pain-related medications increased from pre- to postdiagnosis, including opioids (51.3% vs 55.9%), antiepileptics (22.6% vs 28.6%), and tricyclic antidepressants (15.5% vs 21.2%) (all P <.01). Mean total healthcare costs also increased by $1725 between these periods (mean [95% confidence interval]: $9324 [$8655, $10,092] vs $11,049 [$10,245, $11,973], respectively; P <.01). CONCLUSIONS: Patients with FM are often seen for other medical problems prior to initial diagnosis. Levels of healthcare utilization and costs are high during both the pre- and postdiagnosis periods.

Risk of hospitalization for neutropenic complications of chemotherapy in patients with primary solid tumors receiving pegfilgrastim or filgrastim prophylaxis: a retrospective cohort study.

BACKGROUND: In a meta-analysis of data from randomized trials, the risk of febrile neutropenia during myelosuppressive chemotherapy was reported to be lower with pegfilgrastim prophylaxis than filgrastim prophylaxis. However, there is limited information on the comparative effectiveness of these agents in clinical practice. OBJECTIVE: This study was undertaken to compare the risks of hospitalization for neutropenic complications of chemotherapy in US clinical practice in patients with primary solid tumors receiving pegfilgrastim or filgrastim prophylaxis. METHODS: This was a retrospective cohort study employing a US health insurance database. The source population included all patients who received chemotherapy for a primary solid tumor between January 2003 and December 2005 and who received filgrastim or pegfilgrastim during their first course of chemotherapy. All unique chemotherapy cycles were identified for each patient, and cycles in which pegfilgrastim or filgrastim was administered by cycle day 5 (considered to represent prophylaxis) were selected and pooled for analysis. The risks of hospitalization for neutro-penic complications (using both narrow and broad criteria) and for any reason were then compared between cycles in which filgrastim or pegfilgrastim prophylaxis was administered. Generalized estimating equations were used to control for potential confounding variables. RESULTS: Filgrastim prophylaxis was used in 1193 unique chemotherapy cycles (mean [SD] number of days per cycle, 4.5 [3.3]); for pegfilgrastim prophylaxis, the number of unique chemotherapy cycles was 14,570. First-cycle use represented 16% of all cycles analyzed. The mean ages of patients receiving filgrastim and pegfilgrastim prophylaxis were 61 and 60 years, respectively. Breast cancer was the most common tumor type (52% and 51%), followed by non-Hodgkin's lymphoma (21% and 18%) and lung cancer (11% and 15%). Hospitalization for neutropenic complications (narrow criterion) occurred during 2.1% of filgrastim cycles and 1.2% of pegfilgrastim cycles; hospitalization for neutropenic complications (broad criterion) occurred in a respective 4.8% and 3.1% of cycles; and hospitalization for all causes occurred in 8.7% and 6.3% of cycles (all, P < 0.01). The risks of hospitalization were consistently lower for chemotherapy cycles that involved pegfilgrastim prophylaxis compared with filgrastim prophylaxis (odds ratios = 0.64-0.73; P < 0.05). CONCLUSION: The risk of hospitalization for neutro-penic complications during cancer chemotherapy in clinical practice was approximately one third higher among patients who received filgrastim prophylaxis than among those who received pegfilgrastim prophylaxis.

Cost effectiveness of breast cancer screening with contrast-enhanced MRI in high-risk women.

PURPOSE: The aim of this study was to estimate the cost effectiveness of breast cancer screening with contrast-enhanced magnetic resonance imaging (MRI), with and without adjunctive x-ray mammography (XM), compared with XM alone in high-risk women. MATERIALS AND METHODS: A model was developed to depict the consequences of screening with MRI and/or XM for cohorts of 10,000 women with BRCA1/2 mutations and women with other high-risk characteristics, respectively. The model predicted the number of women correctly and incorrectly diagnosed with each strategy and lifetime consequences in terms of additional care, patient utilities, life expectancy, and quality-adjusted life-years (QALYs). Cost effectiveness was calculated in terms of cost per QALY gained. RESULTS: Among the 400 women (of 10,000) with BRCA1/2 mutations and undiagnosed breast cancer, 361 cases would be detected with MRI and XM, 290 with MRI, and 160 with XM. False-positive results would total 1,526, 1,190, and 528, respectively. Cost per QALY gained with MRI and XM compared with XM alone for women with BRCA1/2 mutations was $25,277. Among other high-risk women, cost per QALY gained with MRI and XM compared with XM alone varied depending on the prevalence of breast cancer, ranging from $45,566 (300 cases) to $310,616 (50 cases). The cost effectiveness of MRI alone compared with XM alone was similar. CONCLUSION: Screening with MRI, alone or in combination with XM, in women with BRCA1/2 mutations is cost effective by current standards compared with XM alone. In women with other high-risk characteristics, MRI screening may also be cost effective, depending on the expected prevalence of undiagnosed breast cancer at the time of screening.

Characteristics and patterns of healthcare utilization of patients with fibromyalgia in general practitioner settings in Germany.

OBJECTIVE: To examine characteristics and patterns of healthcare utilization of patients with fibromyalgia (FM) under the care of general practitioners (GPs) in Germany. RESEARCH DESIGN AND METHODS: Retrospective cohort study, using a large electronic database with information on GP encounters in Germany (IMS MediPlus). We identified all patients, aged > or =18 years, with any encounters for FM (ICD-10 diagnosis code M79.7) between February 1, 2004 and January 31, 2007. We also constituted a comparison group consisting of randomly selected patients with one or more GP encounters - but none for FM - during this period, who we matched to FM patients based on age and sex. Characteristics and healthcare utilization of patients in the FM and comparison groups were then examined over the 1-year period, February 1, 2006-January 31, 2007. MAIN OUTCOME MEASURES: Prevalence of co-morbidities; use of pain-related pharmacotherapy; number of GP office visits; number of specialist referrals; and number of sick notes (physician-excused absences from work). RESULTS: The study sample consisted of 4983 FM patients and an identical number in the comparison group. Mean age was 58 years; 87% were women. The prevalence of various co-morbidities was greater among FM patients, including painful neuropathies (33% vs. 18% for comparison group) and depression (20% vs. 5%) (both p<0.01); more FM patients also received pain-related pharmacotherapy (67% vs. 28%; p<0.01). Compared with patients in the comparison group, FM patients averaged approximately twice as many GP visits (11.4 [SD=10.1] vs. 5.8 [7.5]), referrals (4.5 [5.2] vs. 2.2 [3.6]), and sick notes (0.6 [1.8] vs. 0.3 [1.1]) (all p<0.01). LIMITATIONS: Information in the study database is limited to GP encounters, and the sensitivity and specificity of our case-finding methods are unknown. CONCLUSIONS: Patients with FM under the care of GPs in Germany have comparatively more co-morbidities and higher levels of healthcare utilization.

Economic consequences of failure of initial antibiotic therapy in hospitalized adults with complicated intra-abdominal infections.

BACKGROUND: Initial antibiotic therapy in hospitalized adults with complicated intra-abdominal infection (cIAI) usually is empiric. We explored the economic consequences of failure of such therapy in this patient population. METHODS: Using a large U.S. multi-institutional database, we identified all hospitalized adults admitted between April 1, 2003, and March 31, 2004; who had any cIAI; underwent laparotomy, laparoscopy, or percutaneous drainage of an intra-abdominal abscess ("surgery"); and received intravenous (IV) antibiotics. Initial therapy was characterized in terms of all IV antibiotics received, on the day of or one day before initial surgery. Antibiotic failure was designated on the basis of the need for reoperation or receipt of other IV antibiotics postoperatively. Switches to narrower spectrum agents and changes in regimen prior to discharge with no other evidence of clinical failure were not counted as antibiotic failures. Using multivariable linear regression, duration of IV antibiotic therapy, hospital length of stay, and total inpatient charges were compared between patients who did and did not fail initial therapy. Mortality was compared using multivariable logistic regression. RESULTS: Among 6,056 patients who met the study entrance criteria, 22.4% failed initial antibiotic therapy. Patients who failed received an additional 5.6 days of IV antibiotic therapy (10.4 total days [95% confidence interval 10.1, 10.8] days vs. 4.8 total days [4.8, 4.9] for those not failing), were hospitalized an additional 4.6 days (11.6 total days [11.3, 11.9] vs. 6.9 total days [6.8, 7.0], respectively), and incurred $6,368 in additional inpatient charges ($16,520 [$16,131, $16,919] vs. $10,152 [$10,027, $10,280]) (all, p < 0.01). They also were more likely to die in the hospital (9.5% vs. 1.3%; multivariable odds ratio 3.58 [95% confidence interval 2.53, 5.06]). CONCLUSIONS: Failure of initial IV antibiotic therapy in hospitalized adults with cIAIs is associated with longer hospitalization, higher hospital charges, and a higher mortality rate.