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Objectives: Optimal postpartum care promotes healthcare utilization and outcomes. This qualitative study investigated the experiences and perceived needs for postpartum care among women in rural communities in Arizona, United States. Methods: We conducted in-depth interviews with thirty childbearing women and analyzed the transcripts using reflexive thematic analysis to gauge their experiences, needs, and factors affecting postpartum healthcare utilization. Results: Experiences during childbirth and multiple structural factors, including transportation, childcare services, financial constraints, and social support, played crucial roles in postpartum care utilization for childbearing people in rural communities. Access to comprehensive health information and community-level support systems were perceived as critical for optimizing postpartum care and utilization. Conclusions for Practice: This study provides valuable insights for policymakers, healthcare providers, and community stakeholders in enhancing postpartum care services for individuals in rural communities in the United States. Significance: What is already known on this subject: Centering postpartum policies and interventions to particular population groups necessitates a comprehensive and nuanced understanding of priority needs. What this study adds: This study sheds light on the distinct experiences and challenges influencing postpartum experiences and healthcare utilization among childbearing individuals in rural communities in the United States. [ABSTRACT FROM AUTHOR]

Purpose: Bone and joint infections, complicated by the burgeoning challenge of antimicrobial resistance (AMR), pose significant public health threats by amplifying the disease burden globally. We leveraged results from the 2019 Global Burden of Disease Study (GBD) to explore the impact of AMR attributed to bone and joint infections in terms of disability-adjusted life years (DALYs), elucidating the contemporary status and temporal trends. Methods: Utilizing GBD 2019 data, we summarized the burden of bone and joint infections attributed to AMR across 195 countries and territories in the 30 years from 1990 to 2019. We review the epidemiology of AMR in terms of age-standardized rates, the estimated DALYs, comprising years of life lost (YLLs) and years lived with disability (YLDs), as well as associations between DALYs and socio-demographic indices. Results: The GBD revealed that DALYs attributed to bone and joint infections associated with AMR have risen discernibly between 1990 and 2019 globally. Significant geographical disparities and a positive correlation with socio-demographic indicators were observed. Staphylococcus aureus infections, Group A Streptococcus, Group B Streptococcus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Enterobacter-related bone and joint infections were associated with the highest DALYs because of a high proportion of antimicrobial resistance. Countries with limited access to healthcare, suboptimal sanitary conditions, and inconsistent antibiotic stewardship were markedly impacted. Conclusions: The GBD underscores the escalating burden of bone and joint infections exacerbated by AMR, necessitating urgent, multi-faceted interventions. Strategies to mitigate the progression and impact of AMR should emphasize prudent antimicrobial usage and robust infection prevention and control measures, coupled with advancements in diagnostic and therapeutic modalities. [ABSTRACT FROM AUTHOR]

In this population-based study, we used the SEER database (1985–2015) to examine survival outcomes in chronic lymphocytic leukemia (CLL) patients followed up to the era of advanced treatments including targeted therapies. Data were extracted for patients 15 years or older with a primary diagnosis of CLL. A period analysis was performed to estimate 5- and 10-year relative survival rates for patients diagnosed during different calendar periods from 1985 to 2015. A mixture cure model was used to examine long-term survivors' proportions among patients diagnosed in 1985–2015 and for two cohorts diagnosed in 2000–2003, followed up to 2012 and 2004–2007, and followed up to 2015. Cox proportional hazard modeling was used for the two cohorts to estimate hazard ratios (HRs) of death adjusted for gender and age. The 5-year and 10-year age-adjusted relative survival rate ranged between 73.7 and 89.4% and from 51.6% to "not reached," respectively, for calendar periods of 1985–1989 to 2010–2014. The long-term survivor proportions varied by age and gender from 0 to 59%. The HRs (95%CI) for the 2004–2007 cohort in comparison to the 2000–2003 cohort were 0.58 (0.43–0.78), 0.58 (0.48–0.70), 0.57 (0.49–0.0.67), 0.68 (0.54–0.85), and 0.83 (0.68–1.02) for the age categories of 45–54, 55–64, 65–74, 75–84, and ≥ 85 years, respectively. Overall, relative survival improved significantly for CLL patients diagnosed between 1985 and 2015. These improvements were markedly better following the introduction of targeted therapies. [ABSTRACT FROM AUTHOR]

Purpose: To examine the outcomes associated with granulocyte colony stimulating factors (G-CSFs) administered as primary versus secondary prophylaxis in setting of bendamustine plus rituximab (BR) regimens. Methods: Eighty-five patients who underwent treatment for non-Hodgkin's lymphoma (NHL) or chronic lymphocytic leukemia (CLL) with BR at the University of Arizona Cancer Center from November 2013 to June 2019 were evaluated through retrospective chart review. Patients were stratified into two groups: those who were given G-CSF for primary prophylaxis (n = 47) and for secondary prophylaxis (n = 38). G-CSF-included filgrastim or pegfilgrastim. The primary endpoints were incidence of febrile neutropenia and grade 3 or 4 neutropenia. Results: Same-day G-CSF compared with next-day G-CSF was the most common G-CSF dosing method utilized in primary and secondary prophylaxis (94% and 100%), respectively. Primary and secondary prophylaxis groups were similar on baseline characteristics (p > 0.05); the primary outcome of FN (p > 0.05); all secondary outcomes (p > 0.05) except for a higher frequency of dose delays in secondary (40%) vs primary prophylaxis patients (13%; p = 0.01), and mean absolute neutrophil counts (ANC) in cycles 1 through 5. With higher ANC levels observed during all cycles in the primary prophylaxis group compared with secondary prophylaxis. Conclusions: In this single-center retrospective study, BR-treated lymphoma and CLL patients receiving primary versus secondary with G-CSF showed similar outcomes except, notably, for chemotherapy dose delays that may put secondary patients at risk for poor treatment outcomes. Further research is needed to evaluate the impact of primary versus secondary prophylaxis on treatment outcomes. [ABSTRACT FROM AUTHOR]

Objective: The Beta-Blocker Evaluation Survival Trial showed no survival benefit for bucindolol in New York Heart Association (NYHA) class III/IV heart failure (HF) with reduced ejection fraction, but subanalyses suggested survival benefits for non-Black subjects and Arg389 homozygotes. We conducted an ex ante economic evaluation of Arg389 targeted treatment with bucindolol versus carvidolol, complementing a previous ex ante economic evaluation of bucindolol preceded by genetic testing for the Arg389 polymorphism, in which genetic testing prevailed economically over no testing. Methods: A decision tree analysis with an 18-month time horizon was performed to estimate the cost effectiveness/cost utility of trajectories of 100%, 50%, and 0% of patients genetically tested for Arg389 and comparing bucindolol with empirical carvedilol treatment as per prior BEST subanalyses. Incremental cost-effectiveness/cost-utility ratios (ICERs/ICURs) were estimated. Results: Race-based analyses for non-White subjects at 100% testing showed a loss of (0.04) life-years and (0.03) quality-adjusted life-years (QALYs) at an incremental cost of $2185, yielding a negative ICER of ($54,625)/life-year and ICUR of ($72,833)/QALY lost; at 50%, the analyses showed a loss of (0.27) life-years and (0.16) QALYs at an incremental cost of $1843, yielding a negative ICER of ($6826)/life-year and ICUR of ($11,519)/QALY lost; at 0%, the analyses showed a loss of (0.33) life-years and (0.30) QALYs at an incremental cost of $1459, yielding a negative ICER of ($4421)/life-year and ICUR of ($4863)/QALY lost. Arg389 homozygote analyses at 100% testing showed incremental gains of 0.02 life-years and 0.02 QALYs at an incremental cost of $378, yielding an ICER of 18,900/life-year and ICUR of $18,900/QALY gained; at 50%, the analyses showed a loss of (0.24) life-years and (0.09) QALYs at an incremental cost of $1039, yielding a negative ICER of ($4329)/life-year and ICUR of ($9336)/QALY lost; at 0%, the analyses showed a loss of (0.33) life-years and (0.30) QALYs at an incremental cost of $1459, yielding a negative ICER of ($4421)/life-year and ICUR of ($4863)/QALY lost. Conclusion: This independent ex ante economic evaluation suggests that genetically targeted treatment with bucindolol is unlikely to yield clinicoeconomic benefits over empirical treatment with carvedilol in NYHA III/IV HF. [ABSTRACT FROM AUTHOR]

Background: Olanzapine, neurokinin-1-receptor-antagonists (NK-1-RA), and thalidomide added to palonosetron + dexamethasone (PALO-DEX) have been evaluated in separate studies as prophylaxis for chemotherapy-induced nausea and vomiting (CINV) due to highly emetogenic chemotherapy (HEC). We conducted a Bayesian network meta-analysis to compare the prophylactic efficacy of these agents in combination with PALO-DEX.Methods: PubMed, Medline/Ovid, Embase, and Clinicaltrials.gov were searched from inception through 22 Mar 2018. Study quality was assessed using the Cochrane methodology. A Bayesian network meta-analysis using random-effects models was used to asses complete response (CR) and rate of no nausea (RNN) in acute, delayed, and overall phases and were expressed as odds ratios (OR) and 95% credible interval (95% CrI). Ranking probabilities of treatments were calculated using the surface under the cumulative ranking curve (SUCRA) to identify the probability of a given treatment as the best option against the worst option.Results: Nine RCTs involving two thousand nine hundred fifty-nine patients were included. The olanzapine-based regimen showed greater CR in the acute, delayed, and overall-phases versus the PALO-DEX regimen (OR = 3.97, 95% CrI = 1.02-19.13; OR = 5.62, 95% CrI = 1.66-28.58; OR = 4.79, 95% CrI = 1.40-24.02, respectively). Additionally, it showed greater RNN than the NK-1-RA-based and the PALO-DEX regimens in the delayed phase only (OR = 2.90, 95% CrI = 1.34-5.15; OR = 4.53, 95% CrI = 1.89-10.55, respectively). Olanzapine-, NK-1-RA-, and thalidomide-based regimens did not differ in CR in the three phases. SUCRA probabilities ranked the olanzapine-based regimen as the best option in terms of CR and RNN, while ranking the NK-1-RA-based regimens as the second best option in terms of CR throughout the three phases.Conclusion: Based on the data included in the analyses, there is insufficient evidence to support adding thalidomide or NK-1-RA to PALO-DEX in preventing CINV induced by HEC. However, adding olanzapine to PALO-DEX achieves better CR and RNN. Olanzapine side-effects and the absence of direct comparisons explain why some guidelines are cautious in suggesting the use of olanzapine. [ABSTRACT FROM AUTHOR]

Background A decade ago, clinical pharmacy was a new concept in hospital settings in Jordan, as evidenced in our 2006/2007 study. Changes in the perceptions, expectations, and experiences of physicians regarding the role of clinical pharmacists need to be investigated. Objective To document physicians' perceptions and expectations of, and experiences with, clinical pharmacists in hospital settings in 2017, and to assess differences in these areas between the 2017 and the 2006/2007 samples. Setting: The study was conducted at four hospitals in the north of Jordan. Method Physicians completed a self-administered questionnaire similar to the one used in our 2006/2007 study, which recorded demographics and assessed physicians' perceptions, expectations, and experiences regarding clinical pharmacists. Data of the 2017 sample were analyzed and compared descriptively to those of the 2006/2007 sample. Main outcome measure Physicians' perceptions, expectations, and experiences of pharmacists in hospital settings in 2017. Results Two hundred and ninety-five physicians completed the questionnaire. Physicians in the 2017 sample were most comfortable with pharmacists suggesting the use of prescription medications such as antibiotics (53.6%). Physicians in the 2017 cohort agreed with the eight expectations stated in the questionnaire. Physicians' experiences with clinical pharmacists improved in 2017 from 2006/2007 in all eight areas evaluated. Conclusion Physicians' perceptions, expectations, and experiences towards the professional role of pharmacists have changed over the past 10 years in Jordan. [ABSTRACT FROM AUTHOR]

Introduction: Randomized clinical trials showed that vildagliptin is well tolerated and leads to clinically meaningful decreases in glycated hemoglobin (HbA1c) and fasting plasma glucose (FPG) both in monotherapy and as add-on therapy in inadequately controlled type 2 diabetes mellitus (T2DM) patients. Nevertheless, there is an increased interest for real-life studies to confirm the clinical trial findings in the setting of a daily clinical practice. The aim of this study was to evaluate the effectiveness and tolerability of vildagliptin in a real-life clinical setting and to explore factors determining drug adherence and T2DM management. Methods: G-FORCE was a prospective, observational, open-label, multi-center study in which T2DM patients were prescribed de novo vildagliptin. Clinical effectiveness was determined by changes in HbA1c and FPG and by the proportion of patients reaching glycemic goal. Data were collected at baseline, after 105 ± 15 days and after 180 ± 15 days. Results: A total of 1230 patients were included in this analysis. Mean age was 63.9 ± 10.8 years, and mean HbA1c and FPG levels were 8.2 ± 1.3% and 171.0 ± 53.3 mg/dL, respectively. At 180 days of treatment, HbA1c and FPG levels decreased to 7.2 ± 1.0% and 141.1 ± 44.0 mg/dL, respectively, while the proportion of patients reaching HbA1c and FPG goals rose from 8.6 to 44.6% and from 14.2 to 42.8%, respectively. Conclusion: In this real-world study, vildagliptin was an effective and safe treatment for T2DM patients already treated with metformin, while the single pill combination of vildagliptin and metformin provides a convenient alternative while ensuring comparable effectiveness and tolerability. Funding: Novartis Pharma. [ABSTRACT FROM AUTHOR]

Purpose: Granulocyte colony-stimulating factors (G-CSFs) are indicated for prophylaxis or management of chemotherapy-induced neutropenia (CIN) and febrile neutropenia (FN). Guidelines recommend G-CSF 24-72 h following chemotherapy; however, some evidence suggests that G-CSF initiated < 24 h may benefit some patients.Methods: MONITOR-GCSF was a prospective, observational, multicenter, pan-European study of 1447 chemotherapy-treated patients receiving daily biosimilar (standard) filgrastim (Zarzio®/Zarxio®, filgrastim-sndz, Hexal AG, Sandoz Inc.). In this analysis, cycles were classified as same-day, per-guidelines, or late if G-CSF support was initiated < 24 h, 24-72 h, and > 72 h after chemotherapy. Outcomes included occurrence of CIN of any grade (CIN1/4), grade 3 or 4 (CIN3/4), grade 4 (CIN4), or FN: CIN/FN-related hospitalization or CIN/FN-related chemotherapy disturbance.Results: A total of 5930 chemotherapy cycles from 1423 evaluable patients from MONITOR-GCSF had data for day of G-CSF initiation: 795 cycles (13.4%) classified as same-day, 3320 (56.0%) as per-guidelines, and 1815 (30.6%) as late. Groups did not differ as to CIN1/4 and FN episodes, or CIN/FN-related hospitalizations or chemotherapy disturbances. Patients in the same-day and per-guidelines groups had statistically similar odds of not experiencing any outcomes of interest in any given cycle. Patients in the late group had worse odds of experiencing CIN1/4, CIN3/4, and CIN4 episodes in any given cycle. Proportions of patients reporting clinical events of interest were generally similar.Conclusions: This real-world evidence indicates that CIN/FN prophylaxis initiated with biosimilar filgrastim within 24-72 h post-chemotherapy is effective and safe. Filgrastim administration on the day of chemotherapy may be appropriate in some patients. [ABSTRACT FROM AUTHOR]

Background: Practice patterns of same-day versus next-day pegfilgrastim vary in numerous practice settings across the country. Current utilization with same-day pegfilgrastim reduced overall visits and reduced treatment time for chemotherapy administration.Objective: To assess the efficacy and safety of same-day versus next-day pegfilgrastim in patients with colorectal cancer.Methods: Patient data was extracted through electronic health records (EHR) search of ICD-9 codes that matched patients with CRC and treated with FOLFOX or FOLFIRI from November 2013 to January 2016. The incidence rates of primary and secondary endpoints were estimated for patients who received either FOLFOX or FOLFIRI and same-day pegfilgrastim with 2-sided 95% confidence intervals. Fisher's exact test for 2 × 2 contingency tables was used to compare the incidence of primary and secondary endpoints between the two study groups performed at the α = 0.05 significance level. A study by Hecht et al. served as a historical control for next-day pegfilgrastim.Results: A total of 109 out of an initial 330 patients with appropriate ICD-9 criteria were eligible for study inclusion. The primary endpoint of incidence of FN recorded over 4 chemotherapy cycles with either FOLFOX6 or FOLFIRI occurred in 3.7% of patients (95% CI, 1.1-9.4%). Secondary endpoints also occurred with a relatively low incidence: 13 patients developed grades 3/4 neutropenia (11.9%; 95% CI, 7.0-19.5%); 11 patients required dose reductions because of neutropenia or FN (10.1%; 95% CI, 5.6-17.3%); and 5 patients were hospitalized due to neutropenia or FN (4.6%; 1.7-10.6%). There were 4 reported events of FN (3.2%; 95% CI, 1.0-8.3%) for those who received next-day pegfilgrastim compared to 11 events in the placebo group (9.4%; 95% CI, 5.1-16.4%). The incidence of dose delays or dose reductions due to neutropenia or FN were 5 (4.1%, 95% CI, 1.5-9.4%) in the next-day pegfilgrastim group versus 26 (22.1%, 95% CI, 15.5-30.4%) in the placebo group.Limitations: The study was retrospective in design and utilized a historical control for the comparator.Conclusions: Our study results suggest that same-day pegfilgrastim administration may be a safe and effective alternative to 24-h post-chemotherapy administration in patients with esophageal, gastric, appendiceal, or colorectal cancer undergoing treatment with FOLFOX or FOLFIRI. [ABSTRACT FROM AUTHOR]

Background: Gemcitabine (GEM), oxaliplatin plus GEM (OX + GEM), cisplatin plus GEM (CIS + GEM), capecitabine plus GEM (CAP + GEM), FOLFIRINOX (FFX), and nab-paclitaxel plus GEM (NAB-P + GEM) are the most commonly used regimens as first-line treatment of metastatic pancreatic cancer (MPC) in the UK. Independent economic evaluation of these regimens simultaneously has not been conducted for the UK.Objective: Using data from a network meta-analysis as efficacy measures, we estimated the cost effectiveness and cost utility of these regimens for the UK.Methods: A three-state Markov model (progression-free, progressed-disease, and death) simulating the total costs and health outcomes (quality-adjusted life-years [QALYs] gained and life-years [LYs]) was developed to estimate the incremental cost-utility (ICUR) and incremental cost-effectiveness ratios (ICER) for patients with MPC, from the payer perspective. The model was specified to calculate total costs in 2017 British pounds (GBP, £). All values were discounted at 3.5% per year over a full lifetime horizon. One-way sensitivity and probabilistic sensitivity analyses were conducted to assess the impact of parameter uncertainty on the results.Results: FFX was the most effective regimen, NAB-P + GEM was the most costly regimen, and GEM was the least costly and least effective regimen. OX + GEM, CIS + GEM, and NAB-P + GEM were dominated by CAP + GEM and FFX. Compared with GEM, the ICUR for CAP + GEM and FFX was £28,066 and £33,020/QALY gained, respectively; compared with GEM, the ICER for CAP + GEM and FFX was £17,437 and £22,291/LY gained, respectively; and compared with CAP + GEM, the ICUR and ICER for FFX were £34,947/QALY gained and 24,414/LY gained, respectively.Conclusions: At a threshold value of £30,000/QALY, CAP + GEM was found to be the only cost-effective regimen in the management of MPC in the UK. [ABSTRACT FROM AUTHOR]

Background: Treatments for metastatic pancreatic cancer include monotherapy with gemcitabine (GEM); combinations of GEM with oxaliplatin (OX + GEM), cisplatin (CIS + GEM), capecitabine (CAP + GEM), or nab-paclitaxel (NAB-P + GEM); and the non-GEM combination FOLFIRINOX. Combination therapies have yielded better survival outcomes than GEM alone. A sponsor-independent economic evaluation of these regimens has not been conducted for USA.Objective: The objective of this study was to estimate the cost utility and cost effectiveness of these regimens from the payer perspective for USA.Methods: A three-state Markov model (progression-free, progressed disease, death) simulating the total costs and health outcomes (quality-adjusted life-years; life-years) was developed to estimate the incremental cost-utility and cost-effectiveness ratios. FOLFIRINOX clinical data were obtained from trial and indirect estimates were obtained from network meta-analyses. Lifetime horizon and 3%/year discount rates were used.Results: FOLFIRINOX was the most expensive regimen and GEM the least costly regimen. Compared to GEM, all but one (CIS + GEM) regimen were found to be more effective in quality-adjusted life-years and life-years. Compared to GEM, the incremental cost-utility ratios for CAP + GEM, OX-GEM, NAB-P + GEM, and FOLFIRINOX, were US$180,503, US$197,993, US$204,833, and US$265,718 per additional quality-adjusted life-year, respectively; and the incremental cost-effectiveness ratios were US$88,181, US$87,620, US$135,683, and US$167,040 per additional life-year, respectively. A probabilistic sensitivity analysis confirmed the base-case analysis.Conclusions: This sponsor-independent economic evaluation for USA found that OX + GEM, CAP + GEM, FOLFIRINOX, and NAB-P + GEM, but not CIS + GEM, were more expensive but also more effective than GEM alone in terms of quality-adjusted life-years and life-years gained. The NAB-P + GEM regimen appears to be the most cost effective in USA at a willingness-to-pay threshold of US$200,000/quality-adjusted life-year. [ABSTRACT FROM AUTHOR]

Purpose: In the MONITOR-GCSF study of chemotherapy-induced (febrile) neutropenia with biosimilar filgrastim, 56.6% of patients were prophylacted according to amended EORTC guidelines, but 17.4% were prophylacted below and 26.0% above guideline recommendations.Methods: MONITOR-GCSF is a prospective, observational study of 1447 evaluable patients from 140 cancers centers in 12 European countries treated with myelosuppressive chemotherapy for up to 6 cycles receiving biosimilar GCSF prophylaxis. Patients were classified as under-, correctly-, or over-prophylacted with GCSF relative to guideline recommendations based on their chemotherapy risk, individual risk factors, and type of GCSF prophylaxis (primary versus secondary).Results: Differences between under- (17.4%), correctly- (56.6%), or over-prophylacted (26.0%) groups were found in terms of patient risk factors (age, performance status, history of FN, comorbid conditions) as well as prophylaxis patterns (type of prophylaxis, day of GCSF initiation, and GCSF duration). Rates of chemotherapy-induced neutropenia (CIN) (all grades), FN, and CIN-related hospitalizations were consistently lower in over-prophylacted patients relative to under- and correctly-prophylacted patients. No differences were observed between under- and correctly-prophylacted patients except for CIN/FN-related chemotherapy disturbances. No GCSF safety differences were found between groups (except for headaches).Conclusions: The real-world evidence provided by the MONITOR-GCSF study indicates that providing GCSF support may yield better CIN, FN, and CIN/FN-related hospitalization outcomes if patients are prophylacted at levels above guideline recommendations. Patients who are under-prophylacted are at higher risk for disturbances to their chemotherapy regimens. Our findings support the guideline recommendation that CIN/FN risk be assessed at the beginning of each chemotherapy cycle. [ABSTRACT FROM AUTHOR]

Effect sizes of efficacy of first-line treatments for (metastatic) pancreas cancer are constrained, underscoring the need for evaluations of the efficacy-to-cost relationship. We critically review economic evaluations of first-line chemotherapy regimens for pancreatic cancer since the 1997 introduction of gemcitabine. We searched PubMed/MEDLINE and EMBASE (1997-2015), and the websites of health technology assessment agencies. Two authors independently reviewed economic studies for eligibility in this review; evaluated peer-reviewed, journal-published studies in terms of the Drummond Checklist; and critiqued the technical and scientific merit of all studies. Sixteen pharmacoeconomic evaluations were included: ten published in nine peer-reviewed journals and six on three websites. Six were on single-agent therapies and ten on combination therapies. Analyses conducted included cost-effectiveness (three studies), cost-utility (one study), or combined cost-effectiveness and cost-utility (12 studies). Studies diverged in results, mainly because of different assumptions, methods, inputs, and country-specific guidelines. The two most recent regimens, nanoparticle albumin-bound paclitaxel plus gemcitabine (NAB-P + GEM) and the combination of fluorouracil, oxaliplatin, leucovorin, and irinotecan (FOLFIRINOX), were evaluated in an indirect comparison, yielding a statistically similar benefit in overall survival but superior progression-free survival for FOLFIRINOX. NAB-P + GEM showed greater economic benefit over FOLFIRINOX. In conclusion, the divergence in results observed across studies is attributable to economic drivers that are specific to countries and their healthcare (financing) systems. No recommendations regarding the relative economic benefit of treatment regimens, general or country-specific, are made as the purpose of pharmacoeconomic analysis is to inform policy decision-making and clinical practice, not set policy or define clinical practice. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to examine the real-world treatment patterns and outcomes of chemotherapy-induced (febrile) neutropenia (chemotherapy-induced (CIN)/febrile neutropenia (FN)) prophylaxis with biosimilar filgrastim (Zarzio®).Methods: MONITOR-GCSF is an international (12 countries), multi-center (140), prospective (max. six cycles), observational, open-label, pharmaco-epidemiologic study of cancer patients (n = 1447) treated with myelosuppressive chemotherapy across a total of 6,213 cycles and receiving prophylaxis with Zarzio®. Data were analyzed using both the patient and cycle as unit of analysis.Results: Most (72.3 %) received primary prophylaxis; dosed mainly (53.2 %) at 30 MIU but differentiated by weight, chemotoxicity, and tumor type; and mainly (53.2 %) initiated in the 24-72h post-chemotherapy window but differentiated by prophylaxis type, tumor type, and chemotoxicity and for modal/median duration of 5 days. Relative to European Organisation for Research and Treatment of Cancer (EORTC) guidelines, 56.6 % were correctly prophylacted, 17.4 % under-prophylacted, and 26.0 % over-prophylacted. The following incidence rates were recorded: CIN grade 4 13.2 % of patients and 3.9 % of cycles, FN 5.9 % of patients and 1.4 % of cycles, CIN/FN-related hospitalizations 6.1 % of patients and 1.5 % of cycles, CIN/FN-related chemotherapy disturbances 9.5 % of patients and 2.8 % of cycles, and composite outcomes index 22.3 % of patients and 6.7 % of cycles. Rates varied by type of prophylaxis and tumor, chemotoxicity, initiation day, and prophylaxis duration. There were 1834 musculoskeletal events with 24.7 % of patients reporting bone pain of any grade (mostly mild to moderate), and 148 adverse drug reactions, including 4 serious, were recorded in 76 patients.Conclusions: The clinical and safety outcomes are well within the range of historically reported data for originator filgrastim underscoring the clinical effectiveness and safety of biosimilar filgrastim in daily clinical practice. [ABSTRACT FROM AUTHOR]

The European Medicines Agency (EMA), under a strictly regulated pathway, has approved several biosimilar products since 2005, including biosimilar versions of the erythropoiesis-stimulating agent (ESA) epoetin alfa since 2007. Subsequent to these approvals, the use of biosimilar epoetin alfa in the management of renal anemia has grown steadily throughout Europe. With the enactment of the US Biologics Price Competition and Innovation Act of 2009, a US Food and Drug Administration regulatory approval process for biosimilars was legalized. Thus, biosimilar erythropoietin products are expected to be available for prescription in the USA by mid-decade, presumably at a price that is competitive with the originator brand-name reference products. In this paper, we describe the status of originator and biosimilar ESAs, review the clinical development and regulatory approval of biosimilar erythropoietins in Europe, and summarize relevant efficacy and safety information of biosimilar erythropoietins in relation to their reference products to provide a background for US nephrologists as they appraise biosimilar erythropoietins as treatment options for renal anemia. Key lessons learned from Europe are that (a) EMA-approved biosimilar erythropoietins have comparable efficacy and safety profiles to their reference product erythropoietin; (b) pharmacovigilance preapproval and postapproval are critical, especially with regard to immunogenicity and vascular thromboembolic events; (c) strict preapproval and postapproval requirements must guide the regulatory pathway for biosimilars; and (d) high-quality manufacturing and production processes must be established to ensure quality biosimilar products. The availability of biosimilar erythropoietins in the USA will provide nephrologists with alternative effective, and potentially more affordable, treatment options for patients with renal anemia. [ABSTRACT FROM AUTHOR]

Purpose: Data from an ongoing European pharmacoepidemiological study (MONITOR-CKD5) were used to examine congruence between physician-reported risk-based individualisation of target haemoglobin (Hb) and the actual Hb targets set by these physicians for their patients, as well as actual Hb levels in their patients. Methods: Physician investigators participating in the study completed a questionnaire about their anaemia practice patterns and attitudes post-TREAT at the start of the study (T1) and in summer 2013 (T2). These data were compared with the Hb targets identified at baseline for actual patients ( n = 1197) enrolled in the study. Risk groups included presence/absence of hypertension, diabetes, cardiovascular complications, history of stroke, history of cancer, and age/activity level (elderly/inactive or young/active). Results: At each time point, more than three quarters of physicians responded that results from the TREAT study, in patients not on dialysis, have influenced their use of erythropoiesis-stimulating agents in patients on haemodialysis. At T1, there was a clear difference in physician-reported (theoretical) target Hb levels for patients across the different risk groups, but there was no difference in patients' actual Hb levels across the risk groups. A similar disparity was noted at T2. Conclusions: Physicians' theoretical attitudes to anaemia management in patients on haemodialysis appear to have been influenced by the results of the TREAT study, which involved patients not on dialysis. Physicians claim to use risk-based target Hb levels to guide renal anaemia care. However, there is discrepancy between these declared risk-based target Hb levels and actual target Hb levels for patients with variable risk factors. [ABSTRACT FROM AUTHOR]

Using data from the Belgian Paget's Disease Registry of 142 patients treated with a 5 mg intravenous infusion of zoledronic acid, we examined disease remission over 3 years in 98 patients with Paget disease of bone (PDB) seen in routine practice. Median age was 76 years, most patients (60.2 %) were male, and all were Caucasian. Median time since PDB diagnosis was 11.5 years, few patients (5.1 %) had a family history of PDB, and 32.6 % had received prior bisphosphonate and/or other treatments. The most common pagetic locations were pelvis, spine, femur, tibia, and skull. The most common symptoms included pain, impaired mobility, bone deformities, and joint disease: 36.7 % of patients had comorbid osteoarthritis and 16.3 % comorbid osteoporosis. Response rates were 93.3 % at 1 year, 89.5 % at 2 years, and 91.6 % at 3 years, statistically similar to an extension study of the original zoledronic acid trials. Twenty-one patients experienced a relapse over the 3-year period at a median of 20.7 months posttreatment; of these, 13 regained remission by the end of the observation period. Relapse was not associated with osteoarthritis, osteoporosis, or other comorbidities. Safety data were similar to those reported elsewhere. In summary, in this somewhat frailer sample of patients with PDB, effectiveness and safety data were similar to those observed in the original trial populations. These findings, which are the first on the use of zoledronic acid for PDB in routine clinical practice, underscore the therapeutic benefits and relative safety of zoledronic acid in the management of PDB in 'real-world' clinical settings. [ABSTRACT FROM AUTHOR]

Background Several measures for calculating adherence to one medication from dispensing data records have been proposed, but the nomenclature is inconsistent and computations vary. The same measures, like the medication possession ratio (MPR), have been used for multiple medication regimens, and have tended to over- or under-estimate adherence rates. Objective To demonstrate the impact of varying elements in MPR to a single medication regimen; to define standards for the estimation of adherence to polypharmacy; to propose a new method for calculating adherence to polypharmacy; to face validate it. Setting Face validity of the proposed method. Method Variations in the MPR formula were simulated. Standards for the estimation of adherence to polypharmacy were defined. A new method to calculate adherence to polypharmacy was established. Its face validity with three illustrative cases obtained from a pharmacy refill database was assessed. Main outcome measure Adherence rate to polypharmacy from refill data records. Results MPR to a single medication is operationalized in the numerator and denominator and is influenced by the parameters like observation period, medication gaps, overlap. For polypharmacy, an average MPR is commonly used, which is not accounting for the specificity of multiple medications, and hence overestimating adherence rate. We propose the daily polypharmacy possession ratio (DPPR) as an index of adherence to polypharmacy. It estimates the proportion of time a patient had medication available for use by considering the presence or absence of multiple medications on each day in the observation period. We calculated possession rates from refill histories over 31 months (January 1, 2011-July 31, 2013) for three illustrative patients. The average MPR estimates were 80 % for a patient with 6 medications/20 refill dates, 90 % for a patient with 4 medications/11 refill dates, and 89 % for a patient with 3 medications/17 refill dates. The corresponding DPPRs were 75, 88 and 99 %, indicating overestimations by 5 and 2 %, and underestimation by 10 %, respectively. Conclusion The DPPR accounts for the specificity of polypharmacy including number of medications, medication switching, duplication, overlapping. Research is needed to further confirm the validity of this new index. [ABSTRACT FROM AUTHOR]

Prior longitudinal observational studies have examined the practice patterns and outcomes of anaemia management, including the use of erythropoiesis-stimulating agents (ESAs). Several dimensions of effectiveness remain unaddressed; especially considering the revised ESA label (target Hb levels between 10 and 12 g/dL), the recently published TREAT study, and the European approval of the first ESA biosimilar (HX575). Anecdotal evidence suggests that patient outcomes are influenced by physician-related variables and whether anaemia management is congruent with practice guidelines, but this has not been studied systematically. MONITOR-CKD5 is an international, prospective, observational, pharmacoepidemiological study evaluating the multi-level factors and outcomes of treatment with HX575 for renal anaemia in haemodialysis patients. Driven by a novel, integrated, multi-focal framework for post-approval observational studies, it examines determinants of response at both the patient and the physician level; integrates an advocated statistical methodology here to fore used mainly in the social and behavioural sciences; assesses factors potentially predictive of a poor treatment response; and evaluates the extent to which treatment is congruent with evidence-based guidelines, good practice evidence, and the revised ESA label. This pan-European study will recruit at least 1,000 patients from a minimum of 75 centres, and follow them for up to 24 months following initiation of anaemia management with biosimilar epoetin alfa. MONITOR-CKD5 will not only study the core issues addressed by prior observational studies but also aims to take knowledge discovery a step further by assessing outcomes across varying cohorts of patients, and examining the impact of evidence-based practice on clinical outcomes, differentiating, in the process, between physician-level and patient-level determinants. [ABSTRACT FROM AUTHOR]

Transfusion dependency and iron overload are common among patients with myelodysplastic syndromes (MDS) treated with red blood cell (RBC) transfusions. Transfusion dependency is associated with leukemic progression and shorter survival. Guidelines recommend iron chelation therapy to manage iron overload, however little is known about the chelation patterns in daily clinical practice. The objective of this multicenter, retrospective, cross-sectional, observational study was to evaluate iron status and its management in transfusion-dependent MDS patients. A total of 193 patient records from 29 centers were eligible for inclusion. Median patient age was 76, and median age at diagnosis of MDS was 74. Patients had received an average of 13.4 ± 7.6 RBC units in the past 4 months; 44% had received more than 50 units since their MDS diagnosis. Medium serum ferritin was 1,550 μg/L. Ninety patients (46.6%) received iron chelation therapy with either deferoxamine (41%), deferasirox (36%), and deferoxamine followed by deferasirox (23%). There were no statistically significant differences between chelated and nonchelated patients in terms of International Prognostic Scoring System (IPSS), French-American-British (FAB), and/or World Health Organization (WHO) status, though chelated patients had received more RBC transfusions ( p = 0.014). Iron chelation therapy may be underutilized in transfusion-dependent patients. Undertreatment can be reduced by complementing sound clinical judgment with the generally accepted guidelines of a serum ferritin level >1,000 μg/L and/or two or more RBC transfusions per month for the past year; considering patients on the basis of their IPSS, FAB, and/or WHO status; and individually tailored treatment regimens. Prospective randomized trials are necessary to establish causally the efficacy of iron chelation therapy in MDS. [ABSTRACT FROM AUTHOR]

Goal Of Work: The goal of this study is to test the validity of RESPOND, a web-based decision support system to assess and manage anemia in cancer patients as per the European Organisation for Research and Treatment of Cancer (EORTC) guidelines. The intraclass correlation metrics for the algorithmic definitions were reported previously. Reported here are the concurrent validity, the extent to which clinicians' anemia management is guidelines-congruent when using the system; and discriminant validity, the extent to which clinicians practice in congruence with guidelines when vs. when not using the system.Patients and Methods: Hybrid matched design with precohort (retrospective; clinicians not using RESPOND) and postcohort (prospective; clinicians using RESPOND) of anemic patients matched on cancer type and chemotherapy regimen and followed up over 4 months after treatment initiation with erythropoietic proteins (34 patients per cohort; total N = 68). Congruence scores quantified the extent to which anemia management was congruent with the EORTC guidelines (range 0-10).Main Results: Hemoglobin (Hb) increased significantly for both cohorts, but the postcohort group showed more rapid rate of Hb increase over time (p < 0.006), higher Hb by visit 4 (p = 0.007), and greater Hb increase by visit 4 (p = 0.006). Concurrent validity was high with mean postcohort congruence scores of 8.18 +/- 1.38. Discriminant validity was inferred from statistically significant differences in mean congruence scores between cohorts (p < 0.001) and from the postcohort having odds ratios of 3.64 for patients to reach Hb >or= 11 g/dL and 2.91 to achieve Hb >or= 12 g/dL.Conclusions: RESPOND, a validated computerized clinical guidance system with an incremental effect beyond the pharmacotherapeutic effect of erythropoietic proteins, offers clinicians accurate and safe guidance in managing anemia in cancer patients. [ABSTRACT FROM AUTHOR]

Goal: The benefit of supportive care with erythropoiesis-stimulating agents (ESAs) for patients with cancer-related anaemia is well known. However, the European Cancer Anaemia Survey (ECAS, data from 2001) showed that about 60% of cancer patients with anaemia do not receive any treatment. Since ECAS, evidence-based guidelines have provided recommendations for ESA use, but it is not known to what extent current treatment patterns follow these guidelines. To address this issue, the Anaemia Cancer Treatment (A.C.T.) study was initiated. The background to the development of the A.C.T. study and study methodology are described.Materials and Methods: The A.C.T. study is a global, retrospective, pharmacoepidemiologic study of at least 2,560 medical records of anaemic patients with cancer who were previously treated with an ESA from a minimum of 186 centres. Records from patients aged greater than or equal to 18 years with a diagnosis of solid tumour or myeloma or lymphoma and who were started on ESAs 3-12 months before inclusion and followed for 8-10 weeks will be eligible. Factors associated with ESA non-responsiveness will also be evaluated.Main Results: Completion of the European phase of the study is anticipated in late 2007 with the rest of the world closing in late 2007 or early 2008. Publication of findings is anticipated in 2008.Conclusions: By examining the extent to which anaemia management in clinical practice is congruent with best practice guidelines, the A.C.T. study will provide a further foundation for the development of evidence-based supportive cancer care. [ABSTRACT FROM AUTHOR]

As part of the development of a computerized clinical decision support system for anemia management in cancer patients, we applied psychometric principles and techniques to assess the accuracy of the algorithmic operationalizations of a set of evidence-based practice guidelines. In an iterative rating process, five medical and nursing experts rated 27 algorithmic sets derived from 18 guidelines, the objective being an intraclass coefficient (ICC) exceeding 0.90. The first round of review yielded an ICC of 1.00 for 22 sets. After revision and resubmission to the expert panel, an ICC of 1.00 was obtained for the additional five sets. The evolving decision support system is based on algorithms that accurately specify evidence-based guidelines for anemia management in cancer patients. [ABSTRACT FROM AUTHOR]