A formula for predicting emphysema extent in combined idiopathic pulmonary fibrosis and emphysema.

BACKGROUND: No single pulmonary function test captures the functional effect of emphysema in idiopathic pulmonary fibrosis (IPF). Without experienced radiologists, other methods are needed to determine emphysema extent. Here, we report the development and validation of a formula to predict emphysema extent in patients with IPF and emphysema. METHODS: The development cohort included 76 patients with combined IPF and emphysema at the Royal Brompton Hospital, London, United Kingdom. The formula was derived using stepwise regression to generate the weighted combination of pulmonary function data that fitted best with emphysema extent on high-resolution computed tomography. Test cohorts included patients from two clinical trials (n = 455 [n = 174 with emphysema]; NCT00047645, NCT00075998) and a real-world cohort from the Royal Brompton Hospital (n = 191 [n = 110 with emphysema]). The formula is only applicable for patients with IPF and concomitant emphysema and accordingly was not used to detect the presence or absence of emphysema. RESULTS: The formula was: predicted emphysema extent = 12.67 + (0.92 x percent predicted forced vital capacity) - (0.65 x percent predicted forced expiratory volume in 1 second) - (0.52 x percent predicted carbon monoxide diffusing capacity). A significant relationship between the formula and observed emphysema extent was found in both cohorts (R2 = 0.25, P < 0.0001; R2 = 0.47, P < 0.0001, respectively). In both, the formula better predicted observed emphysema extent versus individual pulmonary function tests. A 15% emphysema extent threshold, calculated using the formula, identified a significant difference in absolute changes from baseline in forced vital capacity at Week 48 in patients with baseline-predicted emphysema extent < 15% versus ≥ 15% (P = 0.0105). CONCLUSION: The formula, designed for use in patients with IPF and emphysema, demonstrated enhanced ability to predict emphysema extent versus individual pulmonary function tests. TRIAL REGISTRATION: NCT00047645; NCT00075998.

Episodic Cost of Lower Respiratory Tract Illness Due to Respiratory Syncytial Virus Among US Infants During the First Year of Life.

A study using two healthcare claims databases (commercial, Medicaid) was undertaken to estimate episodic cost of lower respiratory tract illness due to respiratory syncytial virus (RSV-LRTI) among infants aged <12 months overall, by age, and by birth gestational age (weeks [wGA]). Among commercial-insured infants, mean costs were $28,812 for hospitalized episodes, $2,575 for emergency department episodes, and $336 for outpatient clinic episodes; costs were highest among infants aged <1 month and infants with wGA ≤32, and were comparable-albeit somewhat lower-among Medicaid-insured infants. Cost of RSV-LRTI during acute phase of illness is high, especially among youngest and premature infants.

Clinical Impact of Severe Obesity in Patients with Lymphoedema.

OBJECTIVE: With the rate of obesity increasing worldwide, patients with lymphoedema with and without a concomitant diagnosis of severe obesity (SO) were compared in regard to their baseline demographics, health related characteristics, treatment plans, and patient outcomes. METHODS: This was a retrospective observational cohort study. The IBM MarketScan database was examined (2013 - 2019) for patients with a new diagnosis of lymphoedema. Of 60 284 patients with lymphoedema identified, 6 588 had SO defined by a body mass index > 40 kg/m2. The demographics and other characteristics of SO were compared with patients with lymphoedema without SO. RESULTS: SO and lymphoedema diagnosis increased two fold from 2013 to 2019. The lymphoedema SO+ group was younger (57.8 vs. 60.8 years, p < .001) and with a higher proportion of men (37.7% vs. 24.9%, p < .001) than the lymphoedema SO- group. More comorbidities were observed in the lymphoedema SO+ group than the lymphoedema SO- group: diabetes 46.0% vs. 24.9 % (p < .001), heart failure 18.3% vs. 7.4% (p < .001), hypertension 75.0% vs. 47.6% (p < .001), and renal disease 24.8% vs. 11.9% (p < .001). Use of diuretics in the lymphoedema SO+ group was greater: 57.6% vs. 38.0% (p < .001). Patients with lymphoedema SO+ had higher risk of cellulitis: 34.5% vs. 13.5% (p < .001). Specific lymphoedema treatment was given more often to lymphoedema SO-: 66.3% vs. 64.3% (p = .003). This was significant for manual lymphatic drainage (46.6% vs. 40.0%; p < .001) and physical therapy (55.4% vs. 51.6%; p<.001), but not for compression garments (18.2% vs. 17.7%; p = .38). However, more patients with lymphoedema SO+ received pneumatic compression device treatment: 20.9% vs. 13.7% (p < .001). CONCLUSION: There was an increase in SO associated lymphoedema. Patients with lymphoedema SO+ have over a two and half fold increase in cellulitis incidence, with a significant increase in medical resource use and cost. Despite this, patients with lymphoedema and SO receive less specific therapy such as compression, which has proven to reduce cellulitis incidence.

Under recognition and treatment of lymphedema in head and neck cancer survivors - a database study.

PURPOSE: Head and neck cancer (HNC) will be diagnosed in approximately 54,000 Americans in 2022 with more than 11,000 dying as a result. The treatment of HNC often involves aggressive multimodal therapy including surgery, radiotherapy, and systemic therapy. HNC and its treatments are associated with multiple painful and function-limiting neuromusculoskeletal and visceral long-term and late effects. Among these is head and neck lymphedema (HNL), the abnormal accumulation of protein rich fluid, in as many as 90% of survivors. Though HNL is common and potentially contributory to other function-limiting issues in this population, it is notoriously understudied, underrecognized, underdiagnosed, and undertreated. This study seeks to determine the incidence of HNC-related lymphedema diagnosis and treatment in a large US healthcare claims repository database. METHODS: A retrospective observational cohort design and data from an integrated US healthcare claims repository-the IBM MarketScan Commercial Claims and Encounters (CCAE) and Medicare Supplemental and Coordination of Benefits (MDCR) Databases spanning the period April 1, 2012 through March 31, 2020. RESULTS: Of the 16,654 HNC patients eligible for evaluation, 1,082 (6.5%) with a diagnosis of lymphedema were identified based on eligibility criteria. Of the 521 HNC patients evaluated for lymphedema treatment, 417 (80.0%) patients received 1.5 courses of MLD, 71 (13.6%) patients were prescribed compression garments, and 45 (8.6%) patients received an advanced pneumatic compression device. CONCLUSION: HNL in this population of HNC survivors was underdiagnosed and treated compared with contemporary assessments HNL incidence.

Hemoglobin and End-Organ Damage in Individuals with Sickle Cell Disease.

Background: Sickle cell disease (SCD) is an inherited, chronic, multifaceted blood disorder. Patients with SCD develop anemia, which has been associated with end-organ damage (EOD). Objectives: This retrospective, observational, repeated-measures study systematically characterizes the relationship between hemoglobin (Hb) level and EOD in adolescent and adult patients with SCD. Methods: The study population comprised patients with SCD aged ≥12 years with available Hb data from a US provider-centric health care database. For each patient, each Hb value over time was included as a separate observation. Study outcomes-the onset of any new EOD, including chronic kidney disease, pulmonary hypertension, stroke, and leg ulcer-were ascertained during the 1-year period after each Hb assessment. The association between Hb levels and risk of new EOD was estimated using multivariable generalized estimating equations. Results: A total of 16,043 unique patients with SCD contributed 44,913 observations. Adjusted odds of any EOD during the 1-year follow-up were significantly lower with higher Hb level. Risk reductions with higher Hb levels for chronic kidney disease, pulmonary hypertension, and leg ulcer were comparable. The risk of new EOD was significantly lower among adolescent and adult patients with higher Hb levels. Conclusions: In patients with SCD, higher Hb levels are associated with a reduced risk of developing EOD. Therapeutic strategies that result in higher Hb levels may offer clinical and economic value for patients with SCD. (Curr Ther Res Clin Exp. 2023; 84:XXX-XXX).

Monocyte Count as a Prognostic Biomarker in Patients with Idiopathic Pulmonary Fibrosis.

Rationale: There is an urgent need for simple, cost-effective prognostic biomarkers for idiopathic pulmonary fibrosis (IPF); biomarkers that show potential include monocyte count. Objectives: We used pooled data from pirfenidone and IFNγ-1b trials to explore the association between monocyte count and prognosis in patients with IPF. Methods: This retrospective pooled analysis included patients (active and placebo arms) from the following four phase III, randomized, placebo-controlled trials: ASCEND (NCT01366209), CAPACITY (NCT00287729 and NCT00287716), and INSPIRE (NCT00075998). Outcomes included IPF progression (≥10% absolute decline in FVC% predicted, ≥50 m decline in 6-minute-walk distance, or death), all-cause hospitalization, and all-cause mortality over 1 year. The relationship between monocyte count (defined as time-dependent) and outcomes was assessed using bivariate and multivariable models. Measurements and Main Results: This analysis included 2,067 patients stratified by monocyte count (at baseline: <0.60 × 109 cells/L [n = 1,609], 0.60 to <0.95 × 109 cells/L [n = 408], and ≥0.95 × 109 cells/L [n = 50]). In adjusted analyses, a higher proportion of patients with monocyte counts of 0.60 to <0.95 × 109 cells/L or ≥0.95 × 109 cells/L versus <0.60 × 109 cells/L experienced IPF progression (P = 0.016 and P = 0.002, respectively), all-cause hospitalization (P = 0.030 and P = 0.003, respectively), and all-cause mortality (P = 0.005 and P < 0.001, respectively) over 1 year. Change in monocyte count from baseline was not associated with any of the outcomes over 1 year and did not appear to be affected by study treatment. Conclusions: In patients with IPF, elevated monocyte count was associated with increased risks of IPF progression, hospitalization, and mortality. Monocyte count may provide a simple and inexpensive prognostic biomarker in IPF.

Risk of chemotherapy-induced febrile neutropenia in patients with metastatic cancer not receiving granulocyte colony-stimulating factor prophylaxis in US clinical practice.

OBJECTIVES: To evaluate the use of granulocyte colony-stimulating factor (G-CSF) prophylaxis in US patients with selected metastatic cancers and chemotherapy-induced febrile neutropenia (FN) incidence and associated outcomes among the subgroup who did not receive prophylaxis. METHODS: This retrospective cohort study was conducted at four US health systems and included adults with metastatic cancer (breast, colorectal, lung, non-Hodgkin lymphoma [NHL]) who received myelosuppressive chemotherapy (2009-2017). Patients were stratified by FN risk level based on risk factors and chemotherapy (low/unclassified risk, intermediate risk without any risk factors, intermediate risk with ≥ 1 risk factor [IR + 1], high risk [HR]). G-CSF use was evaluated among all patients stratified by FN risk, and FN/FN-related outcomes were evaluated among patients who did not receive first-cycle G-CSF prophylaxis. RESULTS: Among 1457 metastatic cancer patients, 20.5% and 28.1% were classified as HR and IR + 1, respectively. First-cycle G-CSF prophylaxis use was 48.5% among HR patients and 13.9% among IR + 1 patients. In the subgroup not receiving first-cycle G-CSF prophylaxis, FN incidence in cycle 1 was 7.8% for HR patients and 4.8% for IR + 1 patients; during the course, corresponding values were 16.9% and 15.9%. Most (> 90%) FN episodes required hospitalization, and mortality risk ranged from 7.1 to 26.9% across subgroups. CONCLUSION: In this retrospective study, the majority of metastatic cancer chemotherapy patients for whom G-CSF prophylaxis is recommended did not receive it; FN incidence in this subgroup was notably high. Patients with elevated FN risk should be carefully identified and managed to ensure appropriate use of supportive care.

Decline in Pneumococcal Disease Attenuated in Older Adults and Those With Comorbidities Following Universal Childhood PCV13 Immunization.

BACKGROUND: Following introduction of 7-valent pneumococcal conjugate vaccine (PCV7) in the United States, epidemiology of pneumococcal disease shifted such that disease incidence in the elderly exceeded that in children. We evaluated the impact of replacing PCV7 with PCV13 on disease burden in adults and identified age/risk-specific subgroups with the highest remaining disease burden. METHODS: A retrospective design and data from two US healthcare claims repositories were used. Study population included adults aged ≥18 years and was stratified by age (18-49, 50-64, 65-74, ≥75) and risk profile (healthy, at-risk, high-risk). Rate ratios comparing invasive pneumococcal disease (IPD), all-cause hospitalized pneumonia (ACHP), and pneumococcal pneumonia requiring hospitalization among at-risk and high-risk adults vs healthy counterparts were estimated for 2007-2010 (pre-PCV13), 2011-2012 (peri-PCV13), and 2013-2015 (post-PCV13). RESULTS: Across study periods, IPD and ACHP rates increased with age (2-27 times higher in persons ≥75 vs 18-49) and comorbidity (4-20 times higher in high-risk vs healthy). From pre- to post-PCV13 period, IPD rates declined 5%-48% and ACHP rates declined 4%-19% across age and risk groups (ACHP did not decline in persons ≥75). Decline in IPD and ACHP was attenuated among older adults and those with comorbidities. Accordingly, rate ratios among at-risk and high-risk persons (vs healthy counterparts) increased during the peri- and post-PCV13 periods compared with the pre-PCV13 period. CONCLUSIONS: The switch to PCV13 was associated with large declines in pneumococcal disease among US adults. However, the decline was attenuated with increasing age (and, for ACHP, was absent in persons ≥75) and in those with comorbidities.

Risk and consequences of chemotherapy-induced thrombocytopenia in US clinical practice.

BACKGROUND: Chemotherapy-induced thrombocytopenia (CIT) is a potentially serious complication that can lead to chemotherapy dose delays, dose reductions, or discontinuation, and increases the risk of serious bleeding events. The objectives of this study were to characterize the incidence, clinical consequences, and economic costs of CIT in current US clinical practice. METHODS: A retrospective cohort design and data from two US private healthcare claims repositories (01/2010-12/2016) were employed. Study population comprised adults who received selected myelosuppressive chemotherapy regimens for solid tumors or non-Hodgkin's lymphoma. CIT was identified based on: diagnosis code for thrombocytopenia or bleeding; procedure code for platelet transfusion or bleeding control; or drug code for thrombopoietin-receptor agonist. Incidence of CIT was evaluated during the chemotherapy course (max. no. cycles = 8), and associated consequences and costs (2016US$) were evaluated during the cycle of the CIT episode. RESULTS: Among 215,508 cancer chemotherapy patients, CIT incidence during the course (mean no. cycles = 4.6) was 9.7% (95% CI: 9.6-9.8), and ranged from 6.1% (5.9-6.3) for regimens containing cyclophosphamide to 13.5% (12.7-14.3) for regimens containing gemcitabine; among all patients, incidence was 2.7% (2.6-2.8) in cycle 1, 2.7% (2.6-2.8) in cycle 2, and 2.9% (2.9-3.0) in cycles thereafter. One-third of CIT episodes were managed in hospital, and for the subset of patients hospitalized with a first-listed diagnosis of CIT, mean length of stay was 4.6 (4.4-5.0) days and mean cost of inpatient care was $36,448 (32,332-41,331). Across cycles with CIT, mean cost of CIT-related care was $2179 (2029-2329), comprising $1024 (881-1167) for inpatient care and $1153 (1119-1187) for outpatient care. CONCLUSIONS: In this retrospective evaluation of cancer chemotherapy patients, CIT incidence was high, especially among patients receiving gemcitabine-based regimens, and the costs of CIT-related care were substantial. Accordingly, interventions aimed at identifying and targeting high-risk patients for preventative measures may yield substantial clinical and economic benefits.

Use and effectiveness of pegfilgrastim prophylaxis in US clinical practice:a retrospective observational study.

BACKGROUND: Febrile neutropenia (FN) is a serious complication of myelosuppressive chemotherapy. Clinical practice guidelines recommend routine prophylactic coverage with granulocyte colony-stimulating factor (G-CSF)-such as pegfilgrastim-for most patients receiving chemotherapy with an intermediate to high risk for FN. Patterns of pegfilgrastim prophylaxis during the chemotherapy course and associated FN risks in US clinical practice have not been well characterized. METHODS: A retrospective cohort design and data from two commercial healthcare claims repositories (01/2010-03/2016) and Medicare Claims Research Identifiable Files (01/2007-09/2015) were employed. Study population included patients who had non-metastatic breast cancer or non-Hodgkin's lymphoma and received intermediate/high-risk regimens. Pegfilgrastim prophylaxis use and FN incidence were ascertained in each chemotherapy cycle, and all cycles were pooled for analyses. Adjusted odds ratios for FN were estimated for patients who did versus did not receive pegfilgrastim prophylaxis in that cycle. RESULTS: Study population included 50,778 commercial patients who received 190,622 cycles of chemotherapy and 71,037 Medicare patients who received 271,944 cycles. In cycle 1, 33% of commercial patients and 28% of Medicare patients did not receive pegfilgrastim prophylaxis, and adjusted odds of FN were 2.6 (95% CI 2.3-2.8) and 1.6 (1.5-1.7), respectively, versus those who received pegfilgrastim prophylaxis. In cycle 2, 28% (commercial) and 26% (Medicare) did not receive pegfilgrastim prophylaxis; corresponding adjusted FN odds were comparably elevated (1.9 [1.6-2.2] and 1.6 [1.5-1.8]). Results in subsequent cycles were similar. Across all cycles, 15% of commercial patients and 23% of Medicare patients did not receive pegfilgrastim prophylaxis despite having FN in a prior cycle, and prior FN increased odds of subsequent FN by 2.1-2.4 times. CONCLUSIONS: Notwithstanding clinical practice guidelines, a large minority of patients did not receive G-CSF prophylaxis, and FN incidence was substantially higher among this subset of the population. Appropriate use of pegfilgrastim prophylaxis may reduce patient exposure to this potentially fatal but largely preventable complication of myelosuppressive chemotherapy.

Health-care utilization and expenditures among patients with comorbid bronchiectasis and chronic obstructive pulmonary disease in US clinical practice.

Recent research suggests that bronchiectasis (BE) may be more common than previously believed and that comorbid chronic obstructive pulmonary disease (COPD) is widespread in this patient population. Little is known about the economic burden among patients with BE, and less is known about the burden among those with comorbid BE + COPD. A retrospective matched-cohort design and data from a US health-care claims repository were employed. From the source population comprising adults who had comprehensive medical/drug benefits for ≥1 day in 2013 (i.e. the referent year) and evidence of BE and/or COPD at any time from 2009 to 2013, patients with BE + COPD were age/sex-matched (1:1:1) to patients with BE only and patients with COPD only. For each matched subgroup, annualized levels of respiratory-related and all-cause health-care utilization and expenditures in 2013 were summarized. Source population included 679,679 patients; among those with BE ( n = 31,027), 50% had comorbid COPD. Mean (95% CI) annual levels of respiratory-related utilization and expenditures among matched patients with BE + COPD ( n = 11,685) were higher by 2.4-3.5 times versus patients with BE only and 2.0-2.5 times versus patients with COPD only: hospitalizations, 0.39 (0.37-0.41) versus 0.11 (0.09-0.12) and 0.16 (0.14-0.17); ambulatory encounters, 16.5 (16.1-16.9) versus 6.8 (6.6-7.0) and 8.2 (7.9-8.4); and total expenditures, US$15,685 (14,693-16,678) versus US$5605 (5059-6150) and US$6262 (5655-6868). Respiratory-related utilization and expenditures are high among patients with BE or COPD receiving medical care in US clinical practice and are especially high among those with comorbid BE + COPD receiving medical care, emphasizing the importance of identifying and treating this unique patient population. Funding for this research was provided by RespirTech to Policy Analysis Inc. (PAI).

Metformin Does Not Affect Clinically Relevant Outcomes in Patients with Idiopathic Pulmonary Fibrosis.

BACKGROUND: Diabetes mellitus is a possible risk factor for the development of idiopathic pulmonary fibrosis (IPF), yet the effect of antidiabetic therapy on the course of IPF is unknown. OBJECTIVES: This post hoc analysis assessed the effect of metformin on clinically relevant outcomes in patients with IPF. METHODS: For the primary analysis, patients randomized to placebo (n = 624) in 3 phase 3, double-blind, controlled trials of pirfenidone (CAPACITY [NCT00287716 and NCT00287729]; ASCEND [NCT01366209]) were categorized by baseline metformin use. The primary outcome was disease progression (forced vital capacity [FVC] decline ≥10%, 6-min walking distance [6MWD] decline ≥50 m, or death). Other outcomes included mortality, hospitalization, FVC decline (≥10 and ≥5%), and 6MWD decline. Outcomes were also assessed in patients with diabetes and/or hyperglycemia (impaired glucose tolerance [IGT] and diabetes population [IGT-diabetes population]) and all patients included in the 3 studies (intention-to-treat [ITT] population). RESULTS: Overall, 71 (11.4%) patients were metformin users and 553 (88.6%) were nonmetformin users. Baseline data were similar between groups, except for a higher percentage of males (84.5 vs. 73.2%) and a history of diabetes (98.6 vs. 11.6%) in metformin users versus nonmetformin users. The unadjusted 1-year analyses demonstrated no significant differences in disease progression or other outcomes. A higher proportion of metformin users compared with nonmetformin users had a relative FVC decline of ≥5% (63.4 vs. 50.6%, p = 0.043). Results were similar for the IGT-diabetes population and for the ITT population. Multivariable analyses yielded similar results. CONCLUSIONS: Metformin has no effect on clinically relevant outcomes in patients with IPF.

Effect of Emphysema Extent on Serial Lung Function in Patients with Idiopathic Pulmonary Fibrosis.

RATIONALE: Patients with idiopathic pulmonary fibrosis and emphysema may have artificially preserved lung volumes. OBJECTIVES: In this post hoc analysis, we investigated the relationship between baseline emphysema and fibrosis extents, as well as pulmonary function changes, over 48 weeks. METHODS: Data were pooled from two phase III, randomized, double-blind, placebo-controlled trials of IFN-γ-1b in idiopathic pulmonary fibrosis (GIPF-001 [NCT00047645] and GIPF-007 [NCT00075998]). Patients with Week 48 data, baseline high-resolution computed tomographic images, and FEV1/FVC ratios less than 0.8 or greater than 0.9 (<0.7 or >0.9 in GIPF-007), as well as randomly selected patients with ratios of 0.8-0.9 and 0.7-0.8, were included. Changes from baseline in pulmonary function at Week 48 were analyzed by emphysema extent. The relationship between emphysema and fibrosis extents and change in pulmonary function was assessed using multivariate linear regression. MEASUREMENTS AND MAIN RESULTS: Emphysema was identified in 38% of patients. A negative correlation was observed between fibrosis and emphysema extents (r = -0.232; P < 0.001). In quartile analysis, patients with the greatest emphysema extent (28 to 65%) showed the smallest FVC decline, with a difference of 3.32% at Week 48 versus patients with no emphysema (P = 0.047). In multivariate analyses, emphysema extent greater than or equal to 15% was associated with significantly reduced FVC decline over 48 weeks versus no emphysema or emphysema less than 15%. No such association was observed for diffusing capacity of the lung for carbon monoxide or composite physiologic index. CONCLUSIONS: FVC measurements may not be appropriate for monitoring disease progression in patients with idiopathic pulmonary fibrosis and emphysema extent greater than or equal to 15%.

Effect of statins on disease-related outcomes in patients with idiopathic pulmonary fibrosis.

BACKGROUND: Data are conflicting regarding the possible effects of statins in patients with idiopathic pulmonary fibrosis (IPF). This post hoc analysis assessed the effects of statin therapy on disease-related outcomes in IPF. METHODS: Patients randomised to placebo (n=624) in three controlled trials of pirfenidone in IPF (CAPACITY 004 and 006, ASCEND) were categorised by baseline statin use. Outcomes assessed during the 1-year follow-up included disease progression, mortality, hospitalisation and composite outcomes of death or ≥10% absolute decline in FVC and death or ≥50 m decline in 6-minute walk distance (6MWD). RESULTS: At baseline, 276 (44%) patients were statin users versus 348 (56%) non-users. Baseline characteristics were similar between groups, except statin users were older and had higher prevalence of cardiovascular disease and risk factors. In multivariate analyses adjusting for differences in baseline characteristics, statin users had lower risks of death or 6MWD decline (HR 0.69; 95% CI 0.48 to 0.99, p=0.0465), all-cause hospitalisation (HR 0.58; 95% CI 0.35 to 0.94, p=0.0289), respiratory-related hospitalisation (HR 0.44; 95% CI 0.25 to 0.80, p=0.0063) and IPF-related mortality (HR 0.36; 95% CI 0.14 to 0.95, p=0.0393) versus non-users. Non-significant treatment effects favouring statin use were observed for disease progression (HR 0.75; 95% CI 0.52 to 1.07, p=0.1135), all-cause mortality (HR 0.54; 95% CI 0.24 to 1.21, p=0.1369) and death or FVC decline (HR 0.71; 95% CI 0.48 to 1.07, p=0.1032). CONCLUSIONS: This post hoc analysis supports the hypothesis that statins may have a beneficial effect on clinical outcomes in IPF. Prospective clinical trials are required to validate these observations. TRIAL REGISTRATION NUMBERS: NCT01366209, NCT00287729 and NCT00287716.

The effectiveness and safety of same-day versus next-day administration of long-acting granulocyte colony-stimulating factors for the prophylaxis of chemotherapy-induced neutropenia: a systematic review.

PURPOSE: Granulocyte colony-stimulating factors (G-CSF) are commonly used in clinical practice to prevent febrile neutropenia (FN). US and EU prescribing information and treatment guidelines from the NCCN, ASCO, and EORTC specify that pegfilgrastim, a long-acting (LA) G-CSF, should be administered at least 24 h after myelosuppressive chemotherapy. Nevertheless, many patients receive LA G-CSFs on the same day as chemotherapy. This systematic literature review evaluated the relative merits of same-day versus next-day dosing of LA G-CSFs. METHODS: A broad Ovid MEDLINE® and Embase® literature search was conducted that examined all publications indexed before May 9, 2016 that compared same-day versus next-day LA G-CSF administration. A congress abstract literature search included congresses from January 1, 2011 to April 6, 2016. The parameters for this review were prospectively delineated in a research protocol and adhered to the PRISMA Guidelines. RESULTS: The first part of the systematic literature search identified 1736 publications. After elimination of duplicates, title/abstract screening was conducted on 1440 records, and full text review was conducted on 449 publications. Eleven publications met all criteria and are included in this systematic review; of these, four included data from randomized or single arm prospective studies, and seven were retrospective studies. In most studies included in this review and across a variety of tumor types, administration of pegfilgrastim at least 24 h after myelosuppressive chemotherapy resulted in improved patient outcomes. CONCLUSIONS: Data from multiple publications support administration of pegfilgrastim at least 1 day after chemotherapy.

Burden of Chemotherapy-Induced Febrile Neutropenia Hospitalizations in US Clinical Practice, by Use and Patterns of Prophylaxis with Colony-Stimulating Factor.

INTRODUCTION: Evidence suggests that many cancer chemotherapy patients who are candidates for colony-stimulating factor (CSF) prophylaxis do not receive it or receive it inconsistent with guidelines, and that such patients have a higher risk of febrile neutropenia hospitalization (FNH). Little is known about the number and consequences of FNH by use/patterns of CSF prophylaxis in US clinical practice. METHODS: A retrospective cohort design and private healthcare claims data were employed. Study population comprised adults who received a chemotherapy course with a high-risk regimen, or an intermediate-risk regimen (if ≥1 FN risk factor present), for non-metastatic breast cancer or non-Hodgkin's lymphoma (NHL); each chemotherapy cycle within the course and each FNH episode within the cycles were identified. Consequences included mortality, inpatient days, and costs (US$2013) during FNH. Use (yes/no) and patterns (agent, administration day/duration) of CSF prophylaxis were evaluated within cycles in which FNH episodes occurred. RESULTS: Among all FNH episodes (n=6,355; 109 episodes per 1,000 patients), 41.3% (95% CI: 40.1-42.5) occurred among patients who did not receive CSF prophylaxis in that cycle, and 8.8% (8.1-9.5) occurred among those who received CSF prophylaxis on the same day as chemotherapy. Among FNH episodes occurring in patients who received daily CSF agents (2% of CSF use), 56.1% (44.1-68.0) received prophylaxis <7 days during the cycle. Results for FNH consequences were comparable. CONCLUSIONS: In this retrospective evaluation, one-half of FNH episodes, outcomes, and costs among cancer chemotherapy patients who were candidates for CSF prophylaxis occurred in those who either did not receive it or received it inconsistent with guidelines.

Antacid Therapy and Disease Progression in Patients with Idiopathic Pulmonary Fibrosis Who Received Pirfenidone.

BACKGROUND: Gastroesophageal reflux disease is a potential risk factor for idiopathic pulmonary fibrosis (IPF) progression; however, the impact of antacid therapy (AAT) is under debate. OBJECTIVE: To evaluate the effect of AAT on IPF progression in pirfenidone-treated patients. METHODS: This post hoc analysis included patients with IPF who received pirfenidone in 3 trials (CAPACITY [PIPF-004/PIPF-006] and ASCEND [PIPF-016]). Pulmonary function, exercise tolerance, survival, hospitalizations, and adverse events (AEs) over 52 weeks were analyzed by baseline AAT use. Disease progression was defined as a decrease in forced vital capacity (FVC) of ≥10%, a decrease in 6-min walking distance of ≥50 m, or death over 1 year. RESULTS: Of 623 patients, 44% received AAT. No significant differences were found at 52 weeks (AAT versus non-AAT, respectively) in disease progression (24.9 vs. 30.6%; p = 0.12), all-cause mortality rate (2.9 vs. 4.0%; p = 0.47), IPF-related mortality rate (1.1 vs. 2.0%; p = 0.37), all-cause hospitalization rate (16.1 vs. 18.3%; p = 0.48), or mean change in percent FVC (-2.7 vs. -3.1%; p = 0.44). A relative, but not absolute, FVC decline of ≥10% favored AAT (15 vs. 22%; p = 0.03). Severe gastrointestinal AEs (3.7 vs. 0.9%; p = 0.015) and severe pulmonary infections (3.7 vs. 1.1%; p = 0.035) were more frequent with AAT. CONCLUSIONS: AAT and pirfenidone had outcomes comparable to those of pirfenidone alone in patients with IPF, underscoring the need for prospective trials to elucidate the role of AAT with or without antifibrotic drugs as a treatment for IPF.

Predictors of Mortality Poorly Predict Common Measures of Disease Progression in Idiopathic Pulmonary Fibrosis.

RATIONALE: Mortality prediction is well studied in idiopathic pulmonary fibrosis (IPF), but little is known about predictors of premortality disease progression. Identification of patients at risk for disease progression would be useful for clinical decision-making and designing clinical trials. OBJECTIVES: To develop prediction models for disease progression in IPF. METHODS: In a large clinical trial cohort of patients with IPF (n = 1,113), we comprehensively screened multivariate models of candidate baseline and past-change predictors for disease progression defined by 48-week worsening of FVC, dyspnea (University of California, San Diego Shortness of Breath Questionnaire [UCSD SOBQ]), 6-minute-walk distance (6MWD), and occurrence of respiratory hospitalization, or death. Progression outcomes were modeled as appropriate, by slope change using linear regression models and time to binary outcomes using Cox proportional hazards models. MEASUREMENTS AND MAIN RESULTS: The overall cohort experienced considerable disease progression. Top-performing prediction models did not meaningfully predict most measures of disease progression. For example, prediction modeling explained less than or equal to 1% of the observed variation in 48-week slope change in FVC, UCSD SOBQ, and 6MWD. Models performed better for binary measures of time to disease progression but were still largely inaccurate (cross-validated C statistic ≤0.63 for ≥10% decline in FVC or death, ≤0.68 for ≥20-U increase in UCSD SOBQ or death, ≤0.70 for ≥100 m decline in 6MWD or death). Models for time to respiratory hospitalization or death (C statistic ≤0.77) or death alone (C statistic ≤0.81) demonstrated acceptable discriminative performance. CONCLUSIONS: Clinical prediction models poorly predicted physiologic and functional disease progression in IPF. This is in contrast to respiratory hospitalization and mortality prediction.

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.