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.

Rates and costs of invasive pneumococcal disease and pneumonia in persons with underlying medical conditions.

BACKGROUND: The presence of certain underlying medical conditions is known to increase the risk of pneumococcal disease in persons of all ages and across a wide spectrum of conditions, as demonstrated in two recent evaluations. Corresponding estimates of attributable economic costs have not been well characterized. We thus undertook a retrospective evaluation to estimate rates and costs of pneumococcal disease among children and adults with and without underlying medical conditions in the United States. METHODS: Data were obtained from three independent healthcare claims repositories. The study population included all persons enrolled in participating health plans during 2007-2010, and was stratified into subgroups based on age and risk profile: healthy; at-risk, due to selected comorbid conditions; and high-risk, due to selected immunocompromising conditions. At-risk and high-risk conditions, as well as episodes of invasive pneumococcal disease (IPD) and all-cause pneumonia (PNE), were identified via diagnosis, procedure, and drug codes. Rates and healthcare costs of IPD and PNE (2010US$) among at-risk and high-risk persons were compared with those from age-stratified healthy counterparts using incidence rate ratios (IRR) and cost ratios. RESULTS: Rates of IPD and PNE were consistently higher among at-risk persons (IRR = 4.1 [95 % CI 3.9-4.3] and 4.5 [4.49-4.53]) and high-risk persons (IRR = 10.3 [9.7-11.0] and 8.2 [8.2-8.3]) of all ages versus their healthy counterparts. Rates were notably high for at-risk persons with ≥2 conditions (IRR = 9.0 [8.4-9.7] and 10.3 [10.3-10.4]), as well as those with asthma (IRR = 3.4 [3.0-3.8] and 4.5 [4.47-4.53]) or diabetes (IRR = 4.3 [4.0-4.6] and 4.7 [4.6-4.7]). Healthcare costs totaled $21.7 million per 100,000 at-risk person-years and $58.5 million per 100,000 high-risk person-years, which were 8.7 [8.5-8.8] and 23.4 [22.9-23.8] times higher than corresponding costs for healthy persons. CONCLUSIONS: Rates and costs of IPD and PNE are substantially higher among persons with certain chronic and immunocompromising conditions versus those without any such conditions. Rates and costs for persons with asthma and diabetes were especially increased, and rates and costs for individuals with ≥2 at-risk conditions approached those among persons with high-risk conditions.

Rethinking risk for pneumococcal disease in adults: the role of risk stacking.

Using data from 3 private healthcare claims repositories, we evaluated the incidence of pneumococcal disease among adults with US Advisory Committee on Immunization Practices (ACIP) defined at-risk conditions or rheumatoid arthritis, lupus, Crohn's disease, and neuromuscular disorder/seizures and those with traditional high-risk conditions. We observed that adults with ≥2 concurrent comorbid conditions had pneumococcal disease incidence rates that were as high as or higher than rates observed in those with traditional high-risk conditions.

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.

Prevention of group B streptococcal disease in the first 3 months of life: would routine maternal immunization during pregnancy be cost-effective?

BACKGROUND: A vaccine against group B streptococcus (GBS) that is intended for routine maternal immunization during pregnancy is in clinical development. Addition of vaccination to screening and intrapartum antibiotic prophylaxis (IAP) may further reduce the burden of GBS disease in infancy; its potential cost-effectiveness is unknown, however. METHODS: We evaluated the cost-effectiveness of routine immunization at week 28 of pregnancy with the trivalent GBS (serotypes Ia, Ib and III) vaccine that is in clinical development. The vaccine was assumed to be used in addition to screening and IAP, and reduce the risk of invasive infection in infancy due to covered serotypes. We estimated the effectiveness of immunization in terms of additional cases of GBS disease prevented, deaths averted, life-years saved, and quality-adjusted life-years (QALYs) gained; potential reductions in prematurity and stillbirths were not considered. Costs considered included those of acute care for infants with GBS disease, and chronic care for those with long-term disability. The cost of immunization was assumed to be $100 per person. RESULTS: Assuming 85% coverage, routine maternal immunization against GBS added to screening and IAP would prevent an additional 899 cases of GBS disease and an additional 35 deaths among infants in the US. The total annual cost of immunization would be $362.7 million; estimated cost savings from prevention of GBS disease in infancy would be $43.5 million. The cost-effectiveness of immunization was estimated to be $91,321 per QALY gained. Findings were sensitive to assumptions regarding vaccine efficacy and cost. CONCLUSIONS: Addition of a trivalent GBS maternal vaccine to screening and IAP might further reduce the burden of GBS disease among infants in the US, and may be comparable in cost-effectiveness to other vaccines recently approved for use in children and adolescents.

Risk of pneumococcal disease in children with chronic medical conditions in the era of pneumococcal conjugate vaccine.

BACKGROUND: In the current era of universal immunization of young children with pneumococcal conjugate vaccine, it is unclear whether the high risk ratios for pneumococcal disease previously attributed to specified chronic conditions have persisted. In addition, further analysis of pneumococcal disease risk may clarify whether certain chronic conditions that currently are not specified as significantly increasing the risk of pneumococcal disease should be so considered. METHODS: We conducted a retrospective cohort analysis utilizing healthcare claims data from the period 2007-2010 to compare rates of pneumococcal disease among children <5 and 5-17 years of age with high-risk and at-risk conditions to rates among children without these conditions in the same age group. Risk profiles and manifestations of pneumococcal infection were ascertained from diagnosis, procedure, and drug codes. RESULTS: Among at-risk children, rate ratios for invasive pneumococcal disease (vs children without at-risk/high-risk conditions) were 1.8 (95% confidence interval [CI], 1.4-2.3) in children <5 years of age and 3.3 (95% CI, 2.4-4.4) in children 5-17 years of age. Corresponding rate ratios for high-risk children were 11.2 (95% CI, 7.0-17.9) and 40.1 (95% CI, 28.8-56.0). Rate ratios increased in asthmatic children with increasing disease severity and in all at-risk children by the number of concurrent at-risk conditions. Rate ratios for pneumococcal pneumonia and all-cause pneumonia demonstrated similar patterns. CONCLUSIONS: Children with high-risk and at-risk conditions continue to demonstrate an increased burden of pneumococcal disease. Pneumococcal disease rates are high among asthmatic children with moderate and severe disease and children with multiple at-risk conditions.

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.

Patterns of initial antibiotic therapy for community-acquired pneumonia in U.S. hospitals, 2000 to 2009.

BACKGROUND: Although clinical guidelines for management of community-acquired pneumonia (CAP) in non-intensive care unit ("non-ICU") hospitalized patients have changed substantially over the last decade, it is unknown how treatment of this disease has evolved over this period. METHODS: Using data from >100 U.S. hospitals, we identified all adults (aged ≥18 years) hospitalized for CAP between January 1, 2000, and June 30, 2009 ("study period"). We excluded patients admitted to ICU <24 hours of admission, those not starting antibiotics <24 hours of admission, those not receiving antibiotics for ≥48 hours (if alive), and those with probable healthcare-associated pneumonia. We defined "initial therapy" as all parenteral antibiotics received ≤24 hours of admission, and we examined changes in such therapy over the study period. The statistical significance of changes in initial therapy was ascertained using 2-tailed χ tests. RESULTS: We identified 40,392 patients who met all selection criteria. In 2000, the most frequently used initial regimens were levofloxacin (24.0% of all such admissions), ceftriaxone (9.0%), cefotaxime (7.3%), ceftriaxone plus levofloxacin (3.2%) and azithromycin plus cefotaxime (3.0%); in 2009, they were ceftriaxone plus azithromycin (18.5%), levofloxacin (12.7%), ceftriaxone (6.6%), moxifloxacin (4.7%) and ceftriaxone + levofloxacin (3.2%). Use of single-agent regimens declined between 2000 and 2009 (from 48.2%-30.0%); use of vancomycin almost doubled (13.1%-23.3%). All findings were statistically significant (P < 0.01). CONCLUSIONS: Initial antibiotic therapy for non-ICU CAP has changed substantially in the United States over the past decade, in line with evidence of widespread antibiotic resistance, evolving treatment guidelines and, most recently, quality improvement initiatives that tie hospital payments to guideline-based care.

Rates of pneumococcal disease in adults with chronic medical conditions.

BACKGROUND: Although it is widely accepted that adults with immunocompromising conditions are at greatly increased risk of pneumococcal infection, the extent of risk among immunocompetent adults with chronic medical conditions is less certain, particularly in the current era of universal vaccination of children with pneumococcal conjugate vaccines. METHODS: We conducted a retrospective cohort study using data from 3 healthcare claims repositories (2006-2010) to compare rates of pneumococcal disease in immunocompetent adults with chronic medical conditions ("at-risk") and immunocompromised adults ("high-risk"), with rates in adults without these conditions ("healthy"). Risk profiles and episodes of pneumococcal disease-all-cause pneumonia, pneumococcal pneumonia, and invasive pneumococcal disease (IPD)-were ascertained from diagnosis, procedure, and drug codes. RESULTS: Rates of all-cause pneumonia among at-risk persons aged 18-49 years, 50-64 years, and ≥65 years were 3.2 (95% confidence interval [CI], 3.1-3.2), 3.1 (95% CI, 3.1-3.1), and 3.0 (95% CI, 3.0-3.0) times the rates in age-matched healthy counterparts, respectively. We identified rheumatoid arthritis, systemic lupus erythematosus, Crohn's disease, and neuromuscular or seizure disorders as additional at-risk conditions for pneumococcal disease. Among persons with at-risk conditions, the rate of all-cause pneumonia substantially increased with the accumulation of concurrent at-risk conditions (risk stacking): among persons 18-49 years, rate ratios increased from 2.5 (95% CI, 2.5-2.5) in those with 1 at-risk condition to 6.2 (95% CI, 6.1-6.3) in those with 2 conditions, and to 15.6 (95% CI, 15.3-16.0) in those with ≥3 conditions. Findings for pneumococcal pneumonia and IPD were similar. CONCLUSIONS: Despite widespread use of pneumococcal conjugate vaccines, rates of pneumonia and IPD remain disproportionately high in adults with at-risk conditions, including those with conditions not currently included in the Advisory Committee on Immunization Practices' guidelines for prevention and those with multiple at-risk conditions.

Use of Sildenafil in Pulmonary Arterial Hypertension: Findings from a U.S. Healthcare Claims Database.

Background: Pulmonary arterial hypertension (PAH) is a disease characterized by dyspnea, fatigue, chest pain and syncope. As there is no known cure for PAH, the goal of treatment is to control symptoms and slow disease progression. Sildenafil, a phosphodiesterase-5 inhibitor, has been indicated to improve exercise capacity in PAH in both the United States and the European Union since 2005; since 2009, it also has been indicated in the United States to delay clinical worsening. Patterns of sildenafil use in PAH patients have not been reported. Objectives: To describe patterns of treatment with sildenafil among commercially insured patients in the United States with PAH. Methods: Using a large U.S. healthcare claims database, we identified all patients with evidence of PAH (International Classification of Disease, 9th Revision, Clinical Modification [ICD-9-CM] diagnosis codes 416.0, 416.8) and receipt of sildenafil between January 1, 2005 and September 30, 2008. The date of each patient's earliest pharmacy claim for sildenafil was designated as his or her "index date"; patients with <6 months of data prior to this date were excluded. Post-index use of sildenafil was then examined in terms of the numbers of pharmacy claims and therapy-days, the medication possession ratio (MPR), and the incidence of therapy switching. Results: We identified a total of 855 PAH patients who began sildenafil therapy and met all other entry criteria. Mean (standard deviation [SD]) follow-up was 423.4 (313.0) days. Over this period, these patients averaged 7.1 (6.8) (median, 5) pharmacy dispensings for sildenafil, representing 273.4 (254.8) therapy-days (median, 180). Mean MPR was 71% (median, 83%). Fourteen percent of sildenafil patients switched to another agent during follow-up. Conclusions: In "real-world" clinical practice, many PAH patients beginning treatment with sildenafil remain on therapy for extended periods and are relatively compliant with treatment.

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.

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.

Initial treatment failure in non-ICU community-acquired pneumonia: risk factors and association with length of stay, total hospital charges, and mortality.

OBJECTIVES: To identify risk factors for initial treatment failure in patients with community-acquired pneumonia (CAP) in non-intensive care unit (non-ICU) settings, and to characterize the association between initial treatment failure and length of stay, total hospital charges, and mortality. METHODS: Retrospective cohort study. Using data from >100 US hospitals, this study identified all adults (age ≥18 years) hospitalized for pneumonia between January 1, 2000 and June 30, 2009 who began antibiotic therapy within 24 h of admission and were treated for at least 48 h if alive; patients admitted to intensive care within the first 24 h in hospital were excluded. Initial therapy was defined as all parenteral antibiotics administered within the first 24 h in hospital. Treatment failure was assessed based on subsequent receipt of new antibiotic(s), excluding agents of similar/narrower spectrum and those begun at discharge. Multivariate logistic regression was used to identify risk factors for treatment failure, and multivariate linear and logistic regression to compare length of stay, total hospital charges, and in-hospital mortality between patients experiencing initial treatment failure and those who did not. RESULTS: Among 32,324 patients with non-ICU CAP, 4695 (14.6%) experienced initial treatment failure, most often within 72 h of hospital admission. Significant predictors of initial treatment failure included malnourishment (OR = 1.87; 95% CI = 1.60-2.18), receipt of vasoactive medications within 24 h of admission (1.51 [1.17-1.94]), and renal failure (1.45 [1.32-1.59]). Treatment failure was associated with higher case fatality (8.5% vs 3.3%), longer hospital stays (mean [SD] = 10.1 [8.1] days vs 4.9 [3.3] days), and higher total hospital charges ($37,602 [$71,876] vs $14,371 [$21,633]) (all comparisons, p < 0.01). Study limitations include possible inclusion of patients with healthcare-associated pneumonia (HCAP) in the study sample, our focus on the 40 most commonly used antibiotic regimens, and indirect measurement of treatment failure. CONCLUSIONS: Approximately one in seven non-ICU CAP patients experience failure of initial antibiotic therapy. Risk of failure is higher for patients with significant comorbidities and/or severe infections. Non-ICU patients who experience initial treatment failure have significantly longer hospital stays, higher total hospital charges, and higher rates of mortality.

Initial treatment failure in patients with complicated skin and skin structure infections.

BACKGROUND: Consequences of initial antibiotic failure in patients hospitalized for complicated skin and skin-structure infections (cSSSI) are not well understood. METHODS: Using data from >100 hospitals in the United States, we identified all adults hospitalized for cSSSI between January 1, 2000 and June 30, 2009. We defined "initial therapy" as all parenteral antibiotics administered <24 h of admission, and such therapy was assumed to have failed if the patient (1) received new antibiotic(s) subsequently (excluding similar/narrower spectrum antibiotics or those begun at discharge), or (2) underwent drainage/debridement/amputation>72 h after admission. We limited attention to the 40 most commonly used antibiotic regimens in 2009. We compared clinical and economic outcomes of patients who experienced initial treatment failure and those who did not. RESULTS: The rate of initial treatment failure was 16.6% in acute infections (n=13,498), 34.1% in chronic/ulcerative infections (n=1,116), and 26.7% in surgical site infections (SSIs) (n=2,929). Treatment failure was associated with 4.1-7.3 additional days in the hospital and $11,995-$23,655 in additional inpatient charges; the case fatality rate was from 4- to 12-fold higher in patients who experienced treatment failure than in those who did not (all comparisons, p<0.01). CONCLUSION: Initial treatment failure in patients hospitalized for cSSSI is associated with significantly worse clinical outcomes, longer hospital stays, and higher hospital charges than with successful initial treatment.

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.