Predictors of imminent non-vertebral fracture in elderly women with osteoporosis, low bone mass, or a history of fracture, based on data from the population-based Canadian Multicentre Osteoporosis Study (CaMos).

Using data from the Canadian Multicentre Osteoporosis Study, several risk factors predictive of imminent (2-year) risk of low-trauma non-vertebral fracture among high-risk women were identified, including history of falls, history of low-trauma fracture, poorer physical function, and lower T score. Careful consideration should be given to targeting this population for therapy. PURPOSE: Fracture risk assessment has focused on a long-term horizon and populations with a broad risk range. For elderly women with osteoporosis or low bone mass, or a history of fragility fractures ("high-risk women"), risk prediction over a shorter horizon may have greater clinical relevance. METHODS: A repeated-observations design and data from the Canadian Multicentre Osteoporosis Study were employed. Study population comprised women aged ≥ 65 years with T score (total hip, femoral neck, spine) ≤ - 1.0 or prior fracture. Hazard ratios (HR) for predictors of low-trauma non-vertebral fracture during 2-year follow-up were estimated using multivariable shared frailty model. RESULTS: The study population included 3228 women who contributed 5004 observations; 4.8% experienced low-trauma non-vertebral fracture during the 2-year follow-up. In bivariate analyses, important risk factors included age, back pain, history of falls, history of low-trauma fracture, physical function, health status, and total hip T score. In multivariable analyses, only four independent predictors were identified: falls in past 12 months (≥ 2 falls: HR = 1.9; 1 fall: HR = 1.5), low-trauma fracture in past 12 months (≥ 1 fracture: HR = 1.7), SF-36 physical component summary score (≤ 42.0: HR = 1.6), and total hip T score (≤ - 3.5: HR = 3.7; > - 3.5 to ≤ - 2.5: HR = 2.5; > - 2.5 to ≤ - 1: HR = 1.3). CONCLUSIONS: Imminent risk of low-trauma non-vertebral fracture is elevated among high-risk women with a history of falls or low-trauma fracture, poorer physical function, and lower T score. Careful consideration should be given to identifying and targeting this population for therapy.

Correction to: Treatment patterns in patients with osteoporosis at high risk of fracture in Japan: retrospective chart review.

In this article it was mistakenly stated that Akimitsu Miyauchi is affiliated with both Miyauchi Medical Center, Osaka and Amgen Astellas BioPharma K.K., Tokyo. In fact he is affiliated only with Miyauchi Medical Center; he has no connection with Amgen Astellas.

Treatment patterns in patients with osteoporosis at high risk of fracture in Japan: retrospective chart review.

Osteoporosis (OP) causes reduced bone strength and increases risk of fractures. Medical records from specialist clinics in Japan of postmenopausal women with OP and high risk of fracture were analysed. Majority of patients were treated for OP as recommended and were prescribed OP medications soon after high-risk OP diagnosis. PURPOSE: The incidence of osteoporosis (OP) in Japan is predicted to increase significantly in coming decades. Resultant osteoporotic fractures are a significant contributor of economic and social burden among elderly osteoporosis patients. This retrospective chart review was conducted as a response to the current evidence gap in the treatment patterns for OP patients with high risk of fracture in Japan. METHODS: This was a multi-centre retrospective chart review that analysed data extracted from the medical records of postmenopausal OP patients at high risk for fracture who received care at 11 specialist clinics and medical centers in Japan for at least 18 to 24 months. Main outcome was OP treatment patterns. RESULTS: The study included 709 eligible patients of whom 623 (87.9%) were prescribed OP medication during the study period. The most common reason for not taking OP medication was patient unwillingness to take medication. The most common OP medications prescribed initially were minodronic acid (20.1%), alendronate (19.9%), raloxifene (14.1%), weekly teriparatide acetate (12.4%) and eldecalcitol (11.4%). Majority of patients (62.1%) were still taking their initial medication at the end of the 18-24 month follow-up. CONCLUSIONS: A high percentage of patients (87.9%) in Japan received OP medications soon after their high-risk diagnosis, with bisphosphonates, selective estrogen receptor modulators and teriparatide being the predominant treatment options.

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.

Comparative effectiveness of granulocyte colony-stimulating factors to prevent febrile neutropenia and related complications in cancer patients in clinical practice: A systematic review.

INTRODUCTION: Febrile neutropenia (FN) is a serious side-effect of myelosuppressive chemotherapy. Several clinical trials and observational studies have evaluated the effects of prophylactic granulocyte colony-stimulating factors (G-CSFs) on risk of FN and related complications; however, no systematic reviews have focused on effectiveness in routine clinical practice. Here, we perform a systematic review assessing the comparative effectiveness of prophylaxis with a long-acting G-CSF (pegfilgrastim) versus short-acting G-CSFs (filgrastim, lenograstim, and filgrastim biosimilars) in cancer patients in real-world clinical settings. METHODS: A systematic review was performed based on a pre-specified protocol and was consistent with the Cochrane Collaboration Handbook (2009) and the Centre for Reviews and Dissemination's Guidance for Undertaking Reviews in Health Care (2011). MEDLINE, Embase, BIOSIS, Cumulative Index to Nursing and Allied Health Literature, and Cochrane Library databases were searched for articles published from January 2002 to June 2014. Congress databases (MASCC/ASCO/ESMO) and Google Scholar were searched for abstracts published from January 2012 to August 2014. Filgrastim (NEUPOGEN®), lenograstim and nivestim (a filgrastim biosimilar) were the only short-acting G-CSFs and pegfilgrastim (Neulasta®) was the only long-acting G-CSF described in eligible studies. Outcomes of interest were FN, FN-related hospitalisation and other FN-related complications (death, chemotherapy dose delays and reductions, antimicrobial treatment, severe neutropenia and costs and resource use). RESULTS: Of 1259 unique records identified, 18 real-world observational studies met predefined inclusion criteria; 15 were retrospective studies, and 3 were prospective studies. Multiple tumour types, chemotherapy regimens and geographical regions were included. Seven studies provided statistical comparisons of the risk of FN; risk of FN among patients receiving prophylaxis with pegfilgrastim versus short-acting G-CSF was significantly lower in three studies, numerically lower in three studies, and numerically higher in one study. Six studies provided statistical comparisons of the risk of FN-related hospitalisation; risk of FN-related hospitalisation among patients receiving prophylaxis with pegfilgrastim versus short-acting G-CSF was significantly lower in all six studies, though some variation was seen in subanalyses. Data for other outcomes were sparse with available results being generally consistent with the results seen for risk of FN and FN-related hospitalisation. CONCLUSIONS: Based on the findings from this review of real-world comparative effectiveness studies, risks of FN and FN-related complications were generally lower for prophylaxis with pegfilgrastim versus prophylaxis with short-acting G-CSFs.

Risk of chemotherapy-induced febrile neutropenia in cancer patients receiving pegfilgrastim prophylaxis: does timing of administration matter?

PURPOSE: Contrary to the approved indication for pegfilgrastim prophylaxis, some patients receive it on the same day as the last administration of chemotherapy in clinical practice, which could adversely impact risk of febrile neutropenia (FN). An evaluation of the timing of pegfilgrastim prophylaxis and FN risk was undertaken. METHODS: A retrospective cohort design and data from two US private health care claims repositories were employed. Study population comprised adults who received intermediate/high-risk chemotherapy regimens for solid tumors or non-Hodgkin's lymphoma (NHL) and received pegfilgrastim prophylaxis in ≥1 cycle; all cycles with pegfilgrastim were pooled for analyses. Odds ratios (OR) for FN during the cycle were estimated for patients who received pegfilgrastim on the same day (day 1) as the last administration of chemotherapy versus days 2-4 from chemotherapy completion. RESULTS: The study population included 45,592 patients who received pegfilgrastim in 179,152 cycles (n = 37,095 in cycle 1); in 12 % of cycles, patients received pegfilgrastim on the same day as chemotherapy. Odds of FN were higher for patients receiving pegfilgrastim prophylaxis on the same day as chemotherapy versus days 2-4 from chemotherapy in cycle 1 (OR = 1.6, 95 % CI = 1.3-1.9, p < 0.001) and all cycles (OR = 1.5, 95 % CI = 1.3-1.6, p < 0.001). CONCLUSIONS: In this large-scale evaluation of adults who received intermediate/high-risk regimens for solid tumors or NHL in US clinical practice, FN incidence was found to be significantly higher among those who received pegfilgrastim prophylaxis on the same day as chemotherapy completion versus days 2-4 from chemotherapy completion, underscoring the importance of adhering to the indicated administration schedule.

Risk of chemotherapy-induced febrile neutropenia with early discontinuation of pegfilgrastim prophylaxis in US clinical practice.

PURPOSE: Accumulating evidence suggests that not all cancer chemotherapy patients who receive first-cycle pegfilgrastim prophylaxis continue to receive it in subsequent cycles and that these patients may be subsequently at higher risk of febrile neutropenia (FN). Additional evidence from US clinical practice is warranted. METHODS: Data from two US private healthcare claims repositories were employed. The source population comprised adults who received "intermediate-risk" or "high-risk" chemotherapy regimens for solid cancers or non-Hodgkin's lymphoma and first-cycle pegfilgrastim prophylaxis. From the source population, all patients who did not receive second-cycle pegfilgrastim prophylaxis ("comparison patients") were matched (1:1) to those who received it ("pegfilgrastim patients") based on cancer, regimen, and propensity score. Odds ratios (OR) for FN-broad and narrow definitions-during the second chemotherapy cycle were estimated for comparison patients versus pegfilgrastim patients using generalized estimating equations. RESULTS: A total of 2245 comparison patients (5.3 % of source population) were matched to pegfilgrastim patients; cohorts were well-balanced on baseline characteristics. Second-cycle FN incidence proportions for comparison and pegfilgrastim patients were 3.8 versus 2.2 % based on broad definition and 2.6 versus 0.8 % based on narrow definition; corresponding OR were 1.7 (95 % CI 1.2-2.5, p = 0.002) and 3.5 (95 % CI 2.0-6.0, p < 0.001). Results were similar within cancer/regimen-subgroups and were robust when using alternative methods for confounding adjustment. CONCLUSIONS: In this retrospective evaluation of cancer chemotherapy patients who received first-cycle pegfilgrastim prophylaxis in US clinical practice, a clinically relevant minority did not receive second-cycle prophylaxis. Second-cycle FN odds among this subset were significantly higher than they were among those who continued prophylaxis.

Hospitalizations for osteoporosis-related fractures: Economic costs and clinical outcomes.

BACKGROUND: Osteoporotic fractures frequently require inpatient care, and are associated with elevated risks of morbidity, mortality, and re-hospitalization. A comprehensive evaluation of healthcare costs, resource utilization, and outcomes associated with osteoporosis (OP)-related fractures treated in US hospitals was undertaken. METHODS: A retrospective analysis using the Premier Perspective Database (2010 - 2013) was conducted. Study population comprised patients aged ≥ 50 years hospitalized with a principal diagnosis of a closed or pathologic fracture commonly associated with OP; the first qualifying hospitalization was designated the "index admission". Patients with evidence of major trauma, malignancy, or other non-OP conditions that may lead to pathologic fracture during the index admission were excluded. Study measures included healthcare costs (in 2013 USD), length of stay (LOS), intensive care unit (ICU) use, and mortality during the index admission, as well as 60-day fracture-related readmission. RESULTS: A total of 268,477 patients were admitted to hospital (n = 548 hospitals) with a principal diagnosis of an OP-related fracture; mean (SD) age was 78 (11) years, 75% were female, 69% had ≥ 2 comorbidities, and 82% of patients had a diagnostic code for accidental fall. Among all OP-related fracture admissions, mean (95% CI) hospital cost was $12,839 (12,784-12,893) and LOS was 5.1 (5.1-5.1) days; during the admission, ICU use was 7.4% (7.3-7.5) and mortality was 1.5% (1.5-1.6), and during the 60-day post-discharge period, fracture-related readmission was 2.3% (2.2-2.4). CONCLUSIONS: Hospital costs associated with the acute treatment of OP-related fractures are substantial, especially among patients with fractures of the hip, femur, and spine. Among patients with vertebral fractures-the second most common reason for admission-mortality and ICU use were notably high, and costs and LOS were higher than among those with non-vertebral fractures (excluding hip). Interventions that are effective in reducing fracture risk have the potential to yield substantial cost savings.

Importance of Risk Factors for Febrile Neutropenia Among Patients Receiving Chemotherapy Regimens Not Classified as High-Risk in Guidelines for Myeloid Growth Factor Use.

BACKGROUND: Clinical practice guidelines recommend prophylaxis in patients with cancer receiving a colony-stimulating factor (CSF) when the risk of febrile neutropenia (FN) is high (>20%). For patients receiving chemotherapy regimens not documented as high-risk, the decision regarding CSF prophylaxis use can be challenging, because some patients may be at high risk based on a combination of the regimen and individual risk factors. METHODS: A retrospective cohort design and US private health care claims data were used. Study subjects received chemotherapy regimens classified as "low" or "intermediate," or unclassified, in terms of FN risk, and were stratified by cancer and regimen. For each subject, the first chemotherapy course, and each cycle and FN episode within the course, were identified. FN incidence proportions were estimated by the presence and number of risk factors and chronic comorbidities. RESULTS: Across the 17 tumor/regimen combinations considered (n=160,304 in total), 74% to 98% of patients had 1 or more risk factor for FN and 41% to 89% had 2 or more. Among patients with 1 or more risk factor, FN incidence ranged from 7.2% to 29.0% across regimens, and the relative risk of FN (vs those without risk factors) ranged from 1.1 (95% CI, 0.8-1.3) to 2.2 (95% CI, 1.5-3.0). FN incidence increased in a graded and monotonic fashion with the number of risk factors and comorbidities. CONCLUSIONS: In this retrospective evaluation of patients with cancer receiving chemotherapy regimens not classified as high-risk for FN in US clinical practice, most patients had 1 or more FN risk factor and many had 2 or more. FN incidence was found to be elevated in these patients, especially those with multiple risk factors.

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.

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.

Prevalence of antibiotic resistance in US hospitals.

The percentage of isolates resistant to essential antibiotics among clinically significant bacterial pathogens was evaluated using data from 80089 qualifying admissions in 19 US hospitals (2007-2010). Percentage resistant was highest for the following pathogen/antibiotic pairs: Enterococcus faecium/vancomycin (87.1% [95% CI 86.0-88.1] of 4024 isolates), Staphylococcus aureus/oxacillin-methicillin (56.8% [56.1-57.4] of 23477 isolates), S. aureus/clindamycin (39.7% [39.1-40.4] of 21133 isolates), Pseudomonas aeruginosa/fluoroquinolones (32.6% [31.8-33.5] of 10982 isolates), and Escherichia coli/fluoroquinolones (31.3% [30.8-31.8] of 30715 isolates). The percentage resistant was 3.9% (3.2-4.9) for E. faecium/daptomycin (n = 2029 isolates). While these results are consistent with those from earlier studies in many respects, the percentage of E. faecium isolates resistant to daptomycin, while still small, is higher than has been reported to date.

Costs associated with febrile neutropenia in the US.

BACKGROUND AND OBJECTIVE: Febrile neutropenia (FN) is a potentially life-threatening condition that may develop in cancer patients treated with myelosuppressive chemotherapy and result in considerable costs. This study was designed to estimate US healthcare utilization and costs in those experiencing FN by location of care, tumour type and mortality. METHODS: Cancer patients who received chemotherapy between 2001 and 2006 were identified from the HealthCore Integrated Research Database®, a longitudinal claims database with enrolment, medical, prescription and mortality information covering 12 health plans and more than 20 million US patients. Patients who experienced FN were prospectively matched using propensity score methods within each tumour type of interest (non-Hodgkin's lymphoma, breast, lung, colorectal and ovarian cancer) to those not experiencing FN. Health resource utilization was compared per patient per month for unique prescriptions and visits (inpatient and outpatient) over the length of follow-up. Healthcare total paid costs adjusted to 2009 US dollars per patient per month were examined by FN group (FN vs non-FN, FN died vs FN survived), by source of care (physician office visit, outpatient services, hospitalization and prescriptions) and by tumour type. The number of unique FN-related encounters (inpatient and outpatient) and the number of patients experiencing at least one FN-related encounter were examined. The costs per encounter were tabulated. FN encounters differ from FN episodes in that a single FN episode may include multiple FN encounters (i.e. a patient is seen multiple times [encounters] for treatment of a single FN event [episode]). RESULTS: A total of 5990 patients each were successfully matched between the FN and non-FN (control) groups. Health resource utilization was generally higher in those with FN than in controls. FN patients incurred greater costs (mean ± SD: $US9628 ± 12 517 per patient-month) than non-FN patients ($US8478 ± 12 978). Chemotherapy comprised the majority of costs for both FN (33.5%) and non-FN (40.6%) patients. The largest cost difference by categorical source of care was for hospitalization (p < 0.001). FN patients who died had the highest mean total costs compared with FN surviving patients ($US21 214 ± 25 596 per patient-month vs $US8227 ± 8850, respectively). Follow-up time for those surviving was, on average, 6.6 months longer. Hospitalization accounted for 53.1% of costs in those experiencing mortality with FN, while chemotherapy accounted for the majority of costs (37.1%) in surviving FN patients. A total of 6574 patients with at least one FN encounter experienced a total of 55 726 unique FN-related encounters, 90% of which were outpatient in nature. The majority of FN-related encounters (79%) occurred during the first chemotherapy course. The average costs for FN encounters were highest for inpatient encounters, $US22 086 ± 43 407, compared with $US985 ± 1677 for outpatient encounters. CONCLUSIONS: The occurrence of FN in cancer patients receiving chemotherapy results in greater healthcare resource utilization and costs, with FN patients who die accounting for the greatest healthcare costs. Most FN patients experience at least one outpatient FN encounter, and the total cost of treatment for FN continues to be high.

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.

Comparative effectiveness of colony-stimulating factors for febrile neutropenia: a retrospective study.

BACKGROUND: Granulocyte colony stimulating factors (G-CSFs) decrease the incidence of febrile neutropenia (FN) in cancer patients receiving myelosuppressive chemotherapy. There are two G-CSFs (pegfilgrastim and filgrastim) that differ in dosing schedules from which oncologists may prescribe. OBJECTIVES: This study aimed to compare the effectiveness of prophylactic pegfilgrastim and filgrastim on the risk of hospitalizations. The secondary objective was to compare the effectiveness of the timing of initiation (prophylactic versus delayed). METHODS: A retrospective study of administrative claims from US commercial payers included adult patients with Non-Hodgkin's lymphoma, breast, or lung cancer, treated with chemotherapy between July 2004 and January 2008. For these patients, the first course of chemotherapy and each unique cycle with use of G-CSF was identified and designated 'prophylaxis' if used within the first 5 days of each cycle, or 'delayed', if after day 5. The risk of neutropenia-related and all-cause hospitalization was evaluated for the pegfilgrastim and filgrastim prophylaxis cohorts and for the prophylaxis and delayed G-CSF initiation cohorts. RESULTS: Among 5,571 patient-cycles identified, 88.9% and 11.1% used pegfilgrastim and filgrastim respectively. The rate of neutropenic hospitalization was 1.1% for pegfilgrastim prophylaxis and 3.5% for filgrastim prophylaxis (P = 0.001). Compared to chemotherapy cycles with filgrastim prophylaxis, those with pegfilgrastim prophylaxis had decreased risk of neutropenia-related (adjusted odds ratio (OR) = 0.38, 95% confidence interval (CI) 0.17-0.83) and all-cause hospitalization (adjusted OR = 0.51, 95% CI 0.31-0.84). The neutropenic hospitalization rate was 1.2% for G-CSF prophylactic initiation and 3.7% for delayed G-CSF initiation (P < 0.001). Chemotherapy cycles with prophylactic initiation of either G-CSF had decreased risk of neutropenia-related (adjusted OR = 0.34, 95% CI 0.21-0.56) and all-cause hospitalization (adjusted OR = 0.67, 95% CI 0.49-0.91) compared with delayed initiation of G-CSF. CONCLUSIONS: Pegfilgrastim prescribed as prophylaxis resulted in lower risk of neutropenia-related and all-cause hospitalizations compared to filgrastim prophylaxis. This reduction was similar for prophylactic G-CSF initiation when compared to delayed G-CSF initiation.

Risk of mortality in patients with cancer who experience febrile neutropenia.

BACKGROUND: Febrile neutropenia (FN) is a serious and potentially life-threatening condition that may develop in patients with cancer who receive myelosuppressive chemotherapy. The risk of mortality from FN is not well characterized in current clinical practice. METHODS: Patients with cancer who were receiving chemotherapy in clinical practice were identified from a large US healthcare claims database, and mortality was confirmed using the National Death Index. Patients with FN had their propensity scores matched within tumor types of interest (non-Hodgkin lymphoma and breast, lung, colorectal, and ovarian cancers) to patients who did not experience FN. Study endpoints of overall mortality (anytime during follow-up), early mortality (during the first 12 months of the first chemotherapy course), and hospitalization were examined using univariate and multivariate techniques. RESULTS: Matched FN and control groups each included 5990 patients, and the average follow-up for both groups was 17.6 months. Crude incidence rates of early mortality were significantly higher for patients with FN compared with controls for all tumor types. Proportional hazards regression demonstrated a significant increase in the risk of overall and early mortality in patients with FN compared with controls (hazard ratio [HR], 1.15 [95% confidence interval, 1.02-1.29] and HR, 1.35 [95% confidence interval, 1.09-1.67], respectively). CONCLUSIONS: The adjusted risk of mortality in patients who experienced FN was at least 15% higher than in comparably matched patients without FN, supporting the inference that infectious complications because of neutropenia resulting from myelosuppressive chemotherapy are clinically important.

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.