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.

Clinical human papillomavirus detection forecasts cervical cancer risk in women over 18 years of follow-up.

PURPOSE: To describe the long-term (≥ 10 years) benefits of clinical human papillomavirus (HPV) DNA testing for cervical precancer and cancer risk prediction. METHODS: Cervicovaginal lavages collected from 19,512 women attending a health maintenance program were retrospectively tested for HPV using a clinical test. HPV positives were tested for HPV16 and HPV18 individually using a research test. A Papanicolaou (Pap) result classified as atypical squamous cells of undetermined significance (ASC-US) or more severe was considered abnormal. Women underwent follow-up prospectively with routine annual Pap testing up to 18 years. Cumulative incidence rates (CIRs) of ≥ grade 3 cervical intraepithelial neoplasia (CIN3+) or cancer for enrollment test results were calculated. RESULTS: A baseline negative HPV test provided greater reassurance against CIN3+ over the 18-year follow-up than a normal Pap (CIR, 0.90% v 1.27%). Although both baseline Pap and HPV tests predicted who would develop CIN3+ within the first 2 years of follow-up, only HPV testing predicted who would develop CIN3+ 10 to 18 years later (P = .004). HPV16- and HPV18-positive women with normal Pap were at elevated risk of CIN3+ compared with other HPV-positive women with normal Pap and were at similar risk of CIN3+ compared with women with a low-grade squamous intraepithelial Pap. CONCLUSION: HPV testing to rule out cervical disease followed by Pap testing and possibly combined with the detection of HPV16 and HPV18 among HPV positives to identify those at immediate risk of CIN3+ would be an efficient algorithm for cervical cancer screening, especially in women age 30 years or older.

Incidence rates of endometrial hyperplasia, endometrial cancer and hysterectomy from 1980 to 2003 within a large prepaid health plan.

Obesity strongly increases the risk of endometrial cancer and is projected to increase current and future endometrial cancer incidence. In order to fully understand endometrial cancer incidence, one should also examine both hysterectomy, which eliminates future risk of endometrial cancer, and endometrial hyperplasia (EH), a precursor that prompts treatment (including hysterectomy). Hysterectomy and EH are more common than endometrial cancer, but data on simultaneous temporal trends of EH, hysterectomy and endometrial cancer are lacking. We used linked pathology, tumor registry, surgery and administrative datasets at the Kaiser Permanente Northwest Health Plan to calculate age-adjusted and age-specific rates, 1980-2003, of EH only (N = 5,990), EH plus hysterectomy (N = 904), hysterectomy without a diagnosis of EH or cancer (N = 14,926) and endometrial cancer (N = 1,208). Joinpoint regression identified inflection points and quantified annual percentage changes (APCs). The EH APCs were -5.3% (95% confidence interval [CI] = -7.4% to -3.2%) for 1980-1990, -12.9% (95% CI = -15.6% to -10.1%) for 1990-1999 and 2.4% (95% CI = -6.6% to 12.2%) for 1999-2003. The EH-plus-hysterectomy APCs were -8.6% (95% CI = -10.6% to -6.5%) for 1980-2000 and 24.5% (95% CI = -16.5% to 85.7%) for 2000-2003. Hysterectomy rates did not significantly change over time. The endometrial cancer APCs were -6.5% (95% CI = -10.3% to -2.6%) for 1980-1988 and 1.4% (95% CI = -0.2% to 3.0%) for 1988-2003. Hysterectomy rates were unchanged, but increased endometrial cancer incidence after 1988 and the reversal, in 1999, of the longstanding decline in EH incidence could reflect the influence of obesity on endometrial neoplasia.

Absolute risk of endometrial carcinoma during 20-year follow-up among women with endometrial hyperplasia.

PURPOSE The severity of endometrial hyperplasia (EH)-simple (SH), complex (CH), or atypical (AH)-influences clinical management, but valid estimates of absolute risk of clinical progression to carcinoma are lacking. Materials and METHODS We conducted a case-control study nested in a cohort of 7,947 women diagnosed with EH (1970-2002) at one prepaid health plan who remained at risk for at least 1 year. Patient cases (N = 138) were diagnosed with carcinoma, on average, 6 years later (range, 1 to 24 years). Patient controls (N = 241) were matched to patient cases on age at EH, date of EH, and duration of follow-up, and they were counter-matched to patient cases on EH severity. After we independently reviewed original slides and medical records of patient controls and patient cases, we combined progression relative risks (AH v SH, CH, or disordered proliferative endometrium [ie, equivocal EH]) from the case-control analysis with clinical censoring information (ie, hysterectomy, death, or left the health plan) on all cohort members to estimate interval-specific (ie, 1 to 4, 5 to 9, and 10 to 19 years) and cumulative (ie, through 4, 9, and 19 years) progression risks. Results For nonatypical EH, cumulative progression risk increased from 1.2% (95% CI, 0.6% to 1.9%) through 4 years to 1.9% (95% CI, 1.2% to 2.6%) through 9 years to 4.6% (95% CI, 3.3% to 5.8%) through 19 years after EH diagnosis. For AH, cumulative risk increased from 8.2% (95% CI, 1.3% to 14.6%) through 4 years to 12.4% (95% CI, 3.0% to 20.8%) through 9 years to 27.5% (95% CI, 8.6% to 42.5%) through 19 years after AH. CONCLUSION Cumulative 20-year progression risk among women who remain at risk for at least 1 year is less than 5% for nonatypical EH but is 28% for AH.

Breast cancer incidence, 1980-2006: combined roles of menopausal hormone therapy, screening mammography, and estrogen receptor status.

BACKGROUND: Breast cancer incidence has been rising since at least 1935-1939, but recent US data reveal a statistically significant decline in breast cancer incidence in 2003 that persisted through 2004. Identifying the specific contributions of the potential causes of this long-term increase and the recent decrease in incidence has been challenging. Marked changes in rates of mammography screening and use of menopausal hormone therapy since 1980 have added further complexity. We examined the potential association between menopausal hormone therapy use and recent changes in breast cancer incidence. METHODS: Using tumor registry, clinical, pathology, and pharmacy data from Kaiser Permanente Northwest, a large prepaid US health plan, we compared age-specific and age-adjusted breast cancer incidence rates (2-year moving averages) with use of screening mammography and dispensed menopausal hormone therapy prescriptions between 1980 and 2006. Temporal changes in incidence rates were assessed via joinpoint regression. RESULTS: A total of 7386 incident invasive breast cancers were diagnosed in plan members from 1980 through 2006. Overall age-adjusted breast cancer incidence rates per 100,000 women rose 25% from the early 1980s (105.6) to 1992-1993 (131.7) and an additional 15% through 2000-2001 (151.3), then dropped by 18% to 2003-2004 (123.6) and edged up slightly in 2005-2006 (126.2). These patterns were largely restricted to women aged 45 years or older and to estrogen receptor-positive (ER+) breast cancers. Incidence rates of ER-negative tumors experienced neither of the rises seen for ER+ tumors but also fell precipitously from 2003 through 2006. Rates of mammography screening sharply increased from 1980 to 1993 but then leveled off, and 75%-79% of women aged 45 years or older received a mammogram at least once every 2 years from 1993 through 2006. Menopausal hormone therapy dispensings, particularly of estrogen-plus-progestin formulations, increased from 1988 to 2002 but then dropped by approximately 75% after 2002. CONCLUSIONS: From 1980 through 2006, quantitative and qualitative trends in breast cancer incidence rates, particularly for ER+ tumors, parallel major changes in patterns of mammography screening and use of menopausal hormone therapy.

Are shorter courses of filgrastim prophylaxis associated with increased risk of hospitalization?

BACKGROUND: In clinical trials in patients receiving myelosuppressive chemotherapy, 10-11 days of prophylaxis with filgrastim has been found to reduce the incidence of febrile neutropenia. In clinical practice, however, many patients receive shorter courses of therapy, even though the effectiveness of this regimen is unknown. OBJECTIVE: To examine the relationship between duration of filgrastim prophylaxis and risk of hospitalization in patients receiving chemotherapy for non-Hodgkin's lymphoma (NHL), breast cancer, or lung cancer. METHODS: Using a large, automated, US healthcare claims database, we identified all adults who received chemotherapy for NHL, breast cancer, or lung cancer between 1998 and 2002. For these patients, we identified their first course of chemotherapy and each unique cycle within that course. We then focused attention on all patient cycles in which filgrastim was administered on or before cycle day 5 (filgrastim prophylaxis). Pooling all such cycles, we examined the relationship between duration of filgrastim prophylaxis and risk of hospitalization for neutropenia or infection and risk of hospitalization for any reason, using generalized estimating equations. RESULTS: Mean +/- SD duration of filgrastim prophylaxis was 6.5 +/- 3.1 days across 332 cycles for 133 NHL patients, 6.1 +/- 2.9 days across 482 cycles for 205 breast cancer patients, and 4.3 +/- 3.1 days across 522 cycles for 260 lung cancer patients. In multivariate analyses, risk of hospitalization for neutropenia or infection was found to decline with each additional day of filgrastim prophylaxis for patients with NHL (OR 0.81; p = 0.003), breast cancer (OR 0.77; p = 0.001), and lung cancer (OR 0.91; p = 0.084). Risk reductions with each additional day of prophylaxis ranged from 15% to 19% for patients with NHL, 17% to 23% for those with breast cancer, and 8% to 9% for those with lung cancer. Similar reductions in risk were noted for all-cause hospitalization. CONCLUSIONS: Among patients with NHL, breast cancer, or lung cancer, shorter courses of filgrastim prophylaxis may increase the risk of hospitalization.

The health care costs of cervical human papillomavirus--related disease.

OBJECTIVE: The purpose of this study was to examine the health care costs of cervical human papillomavirus-related disease in a US health care setting. STUDY DESIGN: We conducted an observational cohort study using 1997 through 2002 administrative and laboratory records from 103,476 female enrollees of the Kaiser Permanente Northwest health plan (Portland, Ore). We examined the cost per case and annual cost per 1000 enrollees for cervical human papillomavirus-related events. RESULTS: A cervical examination with a normal routine papanicolaou smear incurred costs of 57 dollars (95% CI, 57-57). Costs that were associated with abnormal routine screening diagnoses ranged from 299 dollars for atypical squamous cells (95% CI, 245-352) to 2349 dollars for high-grade squamous intraepithelial lesion (95% CI, 1,047-3,650). The costs of histologically confirmed cervical intraepithelial neoplasia ranged from 1026 dollars for cervical intraepithelial neoplasia 1 (95% CI, 862-1191) to 3235 dollars for cervical intraepithelial neoplasia 3 (95% CI, 2051-4419); a cost of 376 dollars (95% CI, 315-436) was associated with false-positive test results. At the level of the health plan, overall annual cervical cancer prevention and treatment costs were 26,415 dollars per 1000 female enrollees, with routine cervical cancer screening accounting for expenditures of 16,746 dollars per 1000 female enrollees, cervical intraepithelial neoplasia accounting for expenditures of 4535 dollars per 1000 female enrollees, cervical cancer accounting for expenditures of 2629 dollars per 1000 female enrollees, and false-positive test results accounting for expenditures of 2394 dollars per 1000 female enrollees. CONCLUSION: These are the first direct estimates of both individual and population level costs of cervical human papillomavirus-related disease in a general US health care setting. Routine cervical cancer screening comprises nearly two thirds of total annual cervical human papillomavirus-related health care costs, with 10% of expenditures dedicated to the treatment of invasive cervical cancer, 17% to the management of cervical precancers, and 9% to dealing with false-positive Papanicolaou test results.

Pap screening in a U.S. health plan.

The U.S. Preventive Services Task Force recommends cervical cancer screening begin with the onset of sexual activity and be repeated at least every 3 years until age 65. Previous studies examining the annual utilization and frequency of Pap screening have relied on patient self-report, found to be less reliable than medical records and administrative data. We estimate the age-specific rate and frequency of Pap screening in a U.S. health plan using 1998-2002 administrative data on 150,052 female enrollees within the Kaiser Permanente Northwest health plan, Portland, OR. We analyze the age-specific rate of cervical and vaginal Pap screening and age-specific proportion of routinely screened women receiving cervical screening at various yearly intervals. Of the enrolled women, 31.2% received a Pap smear in 1998, with utilization highest for ages 25-29 (62.4%). Among routinely screened women, 36% were estimated to receive annual cervical smears, versus 22% biennial, 13% triennial, and 29% less frequent screening. Less frequent screening was observed with increasing age. These are the first age-specific estimates of Pap screening frequency and annual utilization in a general healthcare setting, derived from administrative data, rather than self-report. Overall Pap utilization was lower than found in national surveys based on self-report. Despite limited evidence of benefit from more frequent screening, a substantially higher proportion of women was found to receive annual rather than either biennial or triennial screening. Sporadic screening was also more prevalent than expected based on prior self-reported data. Further opportunities exist for improving screening adherence, even within traditionally less vulnerable populations.