Optimizing Postpartum Care in Rural Communities: Insights from Women in Arizona and Implications for Policy.

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.

Disability-adjusted life years from bone and joint infections associated with antimicrobial resistance: an insight from the 2019 Global Burden of Disease Study.

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.

Economic Evaluation of Three BRAF + MEK Inhibitors for the Treatment of Advanced Unresectable Melanoma With BRAF Mutation From a US Payer Perspective.

BACKGROUND: The combinations of BRAF + MEK inhibitors-encorafenib (ENC) + binimetinib (BIN), cobimetinib (COB) + vemurafenib (VEM), and dabrafenib (DAB) + trametinib (TRA)-are recommended for the treatment of BRAF-mutated advanced melanoma. OBJECTIVE: To assess the cost-effectiveness and cost-utility of ENC + BIN versus COB + VEM versus DAB + TRA from a US payer perspective. METHODS: A Markov model was constructed to simulate a hypothetical cohort over a time horizon of 10 years. The overall survival (OS) and progression-free survival (PFS) curves were independently digitized from a randomized controlled trial for ENC + BIN and fitted using R software. Published and indirectly estimated hazard ratios were used to fit OS and PFS curves for COB + VEM and DAB + TRA. Costs, life-year gains, and quality-adjusted life years (QALYs) associated with the 3 treatment combinations were estimated. A base case analysis and probabilistic sensitivity analysis (PSA) were conducted to estimate the incremental cost-utility ratio (ICUR). A discount rate of 3.5% was applied on cost and outcomes. RESULTS: The ENC + BIN versus COB + VEM comparison was associated with an ICUR of $656 233 per QALY gained. The ENC + BIN versus DAB + TRA comparison was associated with an ICUR of $3 135 269 per QALY gained. The DAB + TRA combination dominated COB + VEM. The base case analysis estimates were confirmed by the PSA estimates. ENC + BIN was the most cost-effective combination at a high willingness-to-pay (WTP) threshold of $573 000 per QALY and $1.5 million/QALY when compared to COB + VEM and DAB + TRA, respectively. CONCLUSION AND RELEVANCE: Given current prices and acceptable WTP thresholds, our study suggests that DAB + TRA is the optimum treatment. In this study, ENC + BIN was cost-effective only at a very high WTP per QALY threshold.

Effectiveness and Safety of Enoxaparin Versus Unfractionated Heparin as Thromboprophylaxis in Hospitalized COVID-19 Patients: Real-World Evidence.

BACKGROUND: Coronavirus 2019 (COVID-19) patients are at risk of thrombosis. Literature that compares the effectiveness of enoxaparin to unfractionated heparin (UFH) in COVID-19 patients is scarce. OBJECTIVE: We aimed to evaluate the effectiveness and safety of enoxaparin compared with UFH when used at their standard/intermediate dosing in COVID-19 patients. METHODS: This was a retrospective study conducted at a large COVID-19 center located in Eastern Province, Saudi Arabia. Confirmed COVID-19 cases (≥18 years old) admitted between January and December 2020 were randomly screened for inclusion. Exclusion criteria were patients receiving therapeutic anticoagulation, on chronic anticoagulation, had active bleeding, a platelet count <25 × 109/L, or an incomplete electronic file. The primary endpoint was the occurrence of any thrombotic event (pulmonary embolism, deep venous thrombosis, stroke, or myocardial infarction) or mortality. Secondary endpoints were major or minor bleeding. We applied inverse propensity score weighting (IPTW) with survival analysis to analyze the primary endpoint. Logistic regression was used for the secondary endpoint. RESULTS: A total of 980 patients were included (enoxaparin, n = 470 and UFH, n = 510) with a mean age (±SD) of 47.7 (± 12.3) for the enoxaparin arm and 52 (±13.9) for the UFH arm. There was a statistically significant difference in the primary endpoint with an adjusted hazard ratio (aHR) of 0.46 (95%CI: 0.22 to 0.96, P = 0.039) in favor of the enoxaparin arm. There was no statistically significant difference in major or minor bleeding rates between the two arms. CONCLUSION AND RELEVANCE: When compared with UFH, enoxaparin was associated with a significant reduction in thrombotic events or mortality among COVID-19 patients. The results need confirmation from randomized controlled trials.

Proof-of-Concept Study of Using Supervised Machine Learning Algorithms to Predict Self-Care and Glycemic Control in Type 1 Diabetes Patients on Insulin Pump Therapy.

OBJECTIVE: Using supervised machine learning algorithms (SMLAs), we built models to predict the probability of type 1 diabetes mellitus patients on insulin pump therapy for meeting insulin pump self-management behavioral (IPSMB) criteria and achieving good glycemic response within 6 months. METHODS: This was a single-center retrospective chart review of 100 adult type 1 diabetes mellitus patients on insulin pump therapy (≥6 months). Three SMLAs were deployed: multivariable logistic regression (LR), random forest (RF), and K-nearest neighbor (k-NN); validated using repeated three-fold cross-validation. Performance metrics included area under the curve-Receiver of characteristics for discrimination and Brier scores for calibration. RESULTS: Variables predictive of adherence with IPSMB criteria were baseline hemoglobin A1c, continuous glucose monitoring, and sex. The models had comparable discriminatory power (LR = 0.74; RF = 0.74; k-NN = 0.72), with the RF model showing better calibration (Brier = 0.151). Predictors of the good glycemic response included baseline hemoglobin A1c, entering carbohydrates, and following the recommended bolus dose, with models comparable in discriminatory power (LR = 0.81, RF = 0.80, k-NN = 0.78) but the RF model being better calibrated (Brier = 0.099). CONCLUSION: These proof-of-concept analyses demonstrate the feasibility of using SMLAs to develop clinically relevant predictive models of adherence with IPSMB criteria and glycemic control within 6 months. Subject to further study, nonlinear prediction models may perform better.

Pharmacy considerations: Use of anti-CD38 monoclonal antibodies in relapsed and/or refractory multiple myeloma.

OBJECTIVE: This article reviews current evidence for the approved anti-CD38 monoclonal antibodies, isatuximab and daratumumab, for the treatment of patients with relapsed and/or refractory multiple myeloma (RRMM) and the implications for pharmacists. DATA SOURCES: We conducted a literature search on PubMed/Medline and other sources using the drug names and the terms CD38, multiple myeloma, and pharmacists. DATA SUMMARY: Monoclonal antibodies targeting the CD38 transmembrane glycoprotein offer a promising treatment approach for patients with RRMM. Isatuximab and daratumumab bind to different epitopes on CD38. In this review, we describe the similarities and differences in their mechanism of action, regulatory labeling, and the current guidelines for isatuximab and daratumumab use in RRMM. We review the current evidence for the efficacy and safety of these agents in combination with pomalidomide or carfilzomib and dexamethasone from the landmark phase 3 clinical trials that led to their approval. We discuss key differences in the eligibility criteria between the clinical trials, and differences in dosing, administration, available formulations, and pre- and post-infusion medications for the two agents. We outline recent data from pharmacoeconomic analyses comparing the cost-effectiveness of isatuximab-based regimens with that of daratumumab-based regimens. A brief overview of other anti-CD38 agents in the pipeline for the treatment of patients with RRMM is presented. CONCLUSIONS: Given that pharmacists play an integral role in driving cost-effective use of drugs without compromising efficacy and safety for the end user, educating pharmacists on the key differences between isatuximab and daratumumab can guide the selection of the appropriate anti-CD38 antibody.

Cost-effectiveness of Favipiravir in moderately to severely ill COVID-19 patients in the real-world setting of Saudi arabian pandemic referral hospitals.

Purpose: We aimed to evaluate the cost effectiveness of Favipiravir treatment versus standard of care (SC) in moderately to severely ill COVID-19 patients from the Saudi healthcare payer perspective. Methods: We used the patient-level simulation method to simulate a cohort of 415 patients with moderate to severe COVID-19 disease who were admitted to two Saudi COVID-19 referral hospitals: 220 patients on Favipiravir and 195 patients on SC. We estimated the incremental cost-effectiveness ratio (ICER) of Favipiravir versus SC in terms of the probability to be discharged alive from hospital and the mean time in days to discharge one patient alive. The model was performed twice: first, using unweighted, and second, using weighted clinical and economic data. Weighting using the inverse weight probability method was performed to achieve balance in baseline characteristics. Results: In the unweighted model, base case (probabilistic) ICER estimates favored Favipiravir at savings of Saudi Riyal (SAR)1,611,511 (SAR1,998,948) per 1% increase in the probability of being discharged alive. As to mean time to discharging one patient alive, ICERs favored Favipiravir at savings of SAR11,498 (SAR11,125). Similar results were observed in the weighted model with savings using Favipiravir of SAR1,514,893 (SAR2,453,551) per 1% increase in the probability of being discharged alive, and savings of SAR11,989 (SAR11,277) for each day a patient is discharged alive. Conclusion: From the payer perspective, the addition of Favipiravir in moderately to severely ill COVID-19 patients was cost-savings over SC. Favipiravir was associated with a higher probability of discharging patients alive and lower daily spending on hospitalization than SC.

Cost-Effectiveness and Economic Burden Analyses on All First-Line Treatments of Chronic Lymphocytic Leukemia.

OBJECTIVES: Several chemoimmunotherapy and targeted treatment regimens are approved as front-line therapies in chronic lymphocytic leukemia. We estimated for the 10-year cost-effectiveness of these treatment regimens and the economic burden of following the estimated risk-stratified 21 040 patients with chronic lymphocytic leukemia diagnosed in 2020 for 10 years. METHODS: A Markov model with 7 exclusive health states was specified over a 10-year time horizon. Treatment effectiveness inputs were obtained from a novel network meta-analysis on the progression-free survival, overall survival curves, and time to next treatment. Costs and utilities inputs were included for each health state for each treatment and discounted at 3.0%/year. Life-years (LYs) and quality-adjusted LYs (QALYs) for each treatment were determined. Using the lowest cost regimen as reference, the incremental cost-effectiveness ratio (ICER) and incremental cost-utility ratio (ICUR) were estimated. The 10-year per-patient cost was determined by risk status and by initial treatment. RESULTS: Venetoclax-plus-obinutuzumab was the lowest cost regimen, hence the reference. Superior in effectiveness to all chemoimmunotherapies, it was cost saving. With the highest effectiveness gains at 6.26 LYs and 5.01 QALYs and despite being the most expensive regimen ($1 298 638 per patient), acalabrutinib-plus-obinutuzumab yielded the best ICER ($409 343/LY gained) and ICUR ($501 236/QALY gained). The remaining ICERs of targeted therapies ranged from $512 101/LY gained to $793 236/LY gained and the ICURs from $579 737/QALY gained to $869 300/QALY gained. The 10-year postdiagnosis low/high (venetoclax-plus-obinutuzumab/acalabrutinib-plus-obinutuzumab) economic burden ranges were $42 690 to $98 665 for low-risk, $141 339 to $326 660 for intermediate-risk, and $273 650 to $632 453 for high-risk patients. CONCLUSIONS: Compared with venetoclax-plus-obinutuzumab, chemoimmunotherapies are associated with less health benefits at higher cost. The targeted therapies achieve greater benefits at higher cost.

Expanded access to anticancer treatments from conversion to biosimilar pegfilgrastim-cbqv in US breast cancer patients.

Aim: To estimate cost-savings from conversion to biosimilar pegfilgrastim-cbqv that could be reallocated to provide budget-neutral expanded access to AC (doxorubicin/cyclophosphamide) and TCH (docetaxel/carboplatin/trastuzumab) in breast cancer (BC) patients. Methods: Simulation modeling in panels of 20,000 BC and 5000 HER2+ (HER2+ BC) patients, varying treatment duration (one-six cycles) and conversion rates (10-100%), to estimate cost-savings and additional AC and TCH treatment that could be provided. Results: In 20,000 patients, cost-savings of $1,083 per-patient per-cycle translate to $21,652,064 (one cycle) to $129,912,397 (six cycles). Savings range from $5,413,016 to $32,478,097, respectively, in the 5000-patient HER2+ BC panel. Conclusion: Conversion to pegfilgrastim-cbqv could save up to $130 million and provide more than 220,000 additional cycles of antineoplastic treatment on a budget-neutral basis to BC patients.

Lay abstract Pegfilgrastim is used to prevent low white blood cell count in patients receiving chemotherapy. Comparable to a generic version of a drug, a biosimilar is a follow-on version of a biologic treatment. We calculated the savings from using biosimilar pegfilgrastim in a hypothetical group of 20,000 patients with breast cancer receiving chemotherapy with AC (doxorubicin/cyclophosphamide). We then computed the number of additional doses of AC chemotherapy that could be purchased with those savings. We did the same for a group of 5000 HER2+ breast cancer patients treated with TCH (docetaxel/carboplatin/trastuzumab). Using biosimilar pegfilgrastim could save $1,083 per patient per cycle. If all patients were treated with biosimilar pegfilgrastim over six cycles, $129.9 million could be saved in the AC group and $32.5 million in the TCH group. This could provide 220,468 additional AC doses and 6981 TCH doses. Biosimilar pegfilgrastim can generate significant savings. These savings can be used to provide additional patients with chemotherapy cost-free.

Retrospective evaluation of safety and effectiveness of same-day pegfilgrastim in patients with lung cancer.

Aim: To determine the incidence of chemotherapy-induced febrile neutropenia (FN) and related outcomes after same-day pegfilgrastim in lung cancer. Materials & methods: This single-center, retrospective study evaluated electronic health records of patients with lung cancer treated between 2013-2018. The main end points were incidence of FN and grade 3/4 neutropenia after the first and across all chemotherapy cycles. Results: A total of 114 patients received same-day pegfilgrastim in 384 cycles. The incidence of FN and grade 3/4 neutropenia was 2.3 and 25% after the first chemotherapy cycle and 1.6 and 10.4% across all cycles, respectively. Conclusion: Same-day prophylactic pegfilgrastim in patients with lung cancer may be a suitable option, owing to its low incidence of FN and related outcomes.

Chemotherapy is intended to kill fast-growing cancer cells but can also kill immune cells that are needed to prevent infections. When too many immune cells are killed by chemotherapy, patients with cancer may experience febrile neutropenia, a serious condition that can lead to death in the most severe cases. To prevent this side effect of chemotherapy, a protein that helps certain immune cells to grow (pegfilgrastim) is administered on the day after chemotherapy. To avoid a second clinic visit the day after receiving chemotherapy, it has become common to administer pegfilgrastim on the same day as chemotherapy. Whether this approach is as effective and safe as next-day administration is currently unclear. This study from the University of Arizona Cancer Center showed that in patients with lung cancer who receive chemotherapy, administration of pegfilgrastim on the same day as chemotherapy is a safe, effective method to prevent febrile neutropenia.

Outcomes and risk factors for delayed-onset postoperative respiratory failure: a multi-center case-control study by the University of California Critical Care Research Collaborative (UC3RC).

BACKGROUND: Few interventions are known to reduce the incidence of respiratory failure that occurs following elective surgery (postoperative respiratory failure; PRF). We previously reported risk factors associated with PRF that occurs within the first 5 days after elective surgery (early PRF; E-PRF); however, PRF that occurs six or more days after elective surgery (late PRF; L-PRF) likely represents a different entity. We hypothesized that L-PRF would be associated with worse outcomes and different risk factors than E-PRF. METHODS: This was a retrospective matched case-control study of 59,073 consecutive adult patients admitted for elective non-cardiac and non-pulmonary surgical procedures at one of five University of California academic medical centers between October 2012 and September 2015. We identified patients with L-PRF, confirmed by surgeon and intensivist subject matter expert review, and matched them 1:1 to patients who did not develop PRF (No-PRF) based on hospital, age, and surgical procedure. We then analyzed risk factors and outcomes associated with L-PRF compared to E-PRF and No-PRF. RESULTS: Among 95 patients with L-PRF, 50.5% were female, 71.6% white, 27.4% Hispanic, and 53.7% Medicare recipients; the median age was 63 years (IQR 56, 70). Compared to 95 matched patients with No-PRF and 319 patients who developed E-PRF, L-PRF was associated with higher morbidity and mortality, longer hospital and intensive care unit length of stay, and increased costs. Compared to No-PRF, factors associated with L-PRF included: preexisiting neurologic disease (OR 4.36, 95% CI 1.81-10.46), anesthesia duration per hour (OR 1.22, 95% CI 1.04-1.44), and maximum intraoperative peak inspiratory pressure per cm H20 (OR 1.14, 95% CI 1.06-1.22). CONCLUSIONS: We identified that pre-existing neurologic disease, longer duration of anesthesia, and greater maximum intraoperative peak inspiratory pressures were associated with respiratory failure that developed six or more days after elective surgery in adult patients (L-PRF). Interventions targeting these factors may be worthy of future evaluation.

Survival trends in chronic lymphocytic leukemia across treatment eras: US SEER database analysis (1985-2017).

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.

Conversion to biosimilar pegfilgrastim-cbqv enables budget-neutral access to FOLFIRINOX treatment for metastatic pancreatic cancer.

Aim: To estimate the cost-savings from conversion to biosimilar pegfilgrastim-cbqv that can be reallocated to provide budget-neutral expanded access to FOLFIRINOX in patients with metastatic pancreatic cancer. Methods: Simulation modeling in a panel of 2500 FOLFIRINOX-treated patients, using varying treatment duration (1-12 cycles) and conversion rates (10-100%), to estimate cost-savings and additional FOLFIRINOX treatment that could be budget neutral. Results: In a 2500-patient panel at 100% conversion, savings of US$6,907.41 per converted patient over 12 cycles of prophylaxis translate to US$17.3 million and could provide 72,273 additional FOLFIRINOX doses or 6023 full 6-month regimens. Conclusion: Conversion to biosimilar CIN/FN prophylaxis can generate significant cost-savings and provide budget-neutral expanded access to FOLFIRINOX treatment for patients with metastatic pancreatic cancer.

Lay abstract Pegfilgrastim is used to prevent low white blood cell count in patients receiving chemotherapy. Comparable to a generic version of a drug, a biosimilar is a follow-on version of a biologic treatment. The authors calculated the savings from using biosimilar pegfilgrastim in a hypothetical group of 2500 patients with metastatic pancreatic cancer and then computed the number of additional doses of FOLFIRINOX chemotherapy that could be purchased with those savings. Using biosimilar pegfilgrastim for 12 cycles could save US$6,907.41 per patient. If all 2500 patients were treated with biosimilar pegfilgrastim, US$17.3 million could be saved. This could provide 72,273 additional FOLFIRINOX doses. Biosimilar pegfilgrastim can generate significant savings to purchase chemotherapy for additional patients cost-free.

Same-day versus next-day pegfilgrastim or pegfilgrastim-cbqv in patients with lymphoma receiving CHOP-like chemotherapy.

Aim: To compare the incidence of febrile neutropenia and related outcomes of prophylactic same-day versus next-day pegfilgrastim/pegfilgrastim-cbqv in patients with lymphoma receiving cyclophosphamide, hydroxydaunorubicin, vincristine, prednisone (CHOP)-like chemotherapy. Methods: Retrospective, real-world, single-institution study. Results: 93 patients received 460 cycles of CHOP-like chemotherapy. The incidence of febrile neutropenia and grade 3/4 chemotherapy-induced neutropenia was 5 and 16.5%, respectively. In 401 cycles pegfilgrastim was administered same-day versus 12 cycles next-day. Febrile neutropenia occurred in 17 cycles versus 0 cycles (p = 1.00) and grade 3/4 chemotherapy-induced neutropenia in 65 cycles (16.2%) versus 1 cycle (16.7%; p = 1.00) with same-day versus next-day pegfilgrastim administration, respectively. Conclusion: Pegfilgrastim may be safely administered on the same day as chemotherapy in patients with lymphoma receiving CHOP-like chemotherapy.

Lay abstract Aside from killing cancer cells, chemotherapy can also affect the growth of immune cells that normally prevent infections. Without enough of these immune cells in the blood, the patient's body cannot fight infections. This can lead to a serious condition called febrile neutropenia, and death in the most severe cases. Pegfilgrastim, a growth factor that helps important types of immune cells to grow, can prevent this side effect of chemotherapy. Usually, pegfilgrastim is administered the day after chemotherapy but there is a trend to administer it on the day of chemotherapy, but whether this is effective and safe is currently unclear. This study from the University of Arizona Cancer Center showed that administration of pegfilgrastim on the same day as chemotherapy is a safe, effective method of preventing febrile neutropenia in patients who receive standard-of-care chemotherapy to treat lymphoma.

Outcomes of primary and secondary prophylaxis of chemotherapy-induced and febrile neutropenia in bendamustine plus rituximab regimens in patients with lymphoma and chronic lymphocytic leukemia: real-world, single-center experience.

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.

Cost Analysis of Adjunctive Hydrocortisone Therapy for Septic Shock: U.S. Payer Perspective.

OBJECTIVES: To conduct a cost analysis of adjunctive hydrocortisone therapy for severe septic shock from the perspective of a third-party payer in the United States. DESIGN: Estimates of outcomes were aggregate data from the Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock and Activated Protein C and Corticosteroids for Human Septic Shock trials. In these trials, the outcomes of interests were ICU length of stay, vasopressor-free days, ventilation-free days, and the proportion of patients receiving blood transfusion. Each outcome was monetized into a set of mutually exclusive components and was aggregated to estimate the cost-per-patient based on each trial. Cost inputs for each outcome were obtained from literature and adjusted based on the medical care consumer price index. To estimate the budget impact using adjunctive hydrocortisone therapy, per-patient avoided cost was multiplied by expected septic shock annual incidence. Deterministic one-way sensitivity analysis evaluated the robustness of the findings, and Monte Carlo simulation estimated 95% CI of the findings. SETTING: A total of 103 medical-surgical ICU (69 for Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock and 34 for Activated Protein C and Corticosteroids for Human Septic Shock). PATIENTS: Adults greater than or equal to 18 years old with septic shock. INTERVENTIONS: Adjunctive hydrocortisone therapy (hydrocortisone at a dose of 200 mg/d for 7 d for Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock and hydrocortisone at a 50 mg IV bolus every 6 hr and fludrocortisone as a 50 µg tablet once daily). MEASUREMENTS AND MAIN RESULTS: Per Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock, adjunctive hydrocortisone therapy showed a 90-day monetized benefit of $8,111 (95% CI, $3,914-$12,307) per patient, driven by improvements in ICU-free days, vasopressor-free days, ventilation-free days, and blood transfusion proportion. The total estimated annual impact of adjunctive hydrocortisone therapy, in 2019 dollars, was $750 million. Per Activated Protein C and Corticosteroids for Human Septic Shock, adjunctive hydrocortisone therapy showed a 90-day monetized benefit of $25,539 per patient (95% CI, $22,853-$28,224), driven by improvements in ICU free-days, vasopressor-free days, and ventilation-free days. The total estimated annual impact of adjunctive hydrocortisone therapy, in 2019 dollars, was $2.3 billion. The deterministic one-way sensitivity analysis showed the cost of ICU stays to be the most influential factor in both analyses. The sensitivity analysis using the reported median showed a greater monetized benefit of $10,658 (Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock) and $30,911 (Activated Protein C and Corticosteroids for Human Septic Shock) per patient. CONCLUSIONS: Using adjunctive hydrocortisone therapy yields a significant monetized benefit based on inputs from the Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock and Activated Protein C and Corticosteroids for Human Septic Shock trials.

Systematic review of longitudinal studies on chemotherapy-associated subjective cognitive impairment in cancer patients.

OBJECTIVES: This systematic review of longitudinal studies, assessing subjective cognitive impairment (SCI) reported by adult cancer patients, aimed to summarize evidence on the impact of chemotherapy on SCI, identify moderators of SCI, and evaluate methodological issues. METHODS: Data accrued from Pubmed, EMBASE, CINAHL, PsychInfo, and the Cochrane library. Inclusion criteria were original studies, an exclusively adult sample, valid and reliable subjective cognitive measures, and at least one baseline data point prior to and another after the initiation of chemotherapy. Data were collected on the sample composition, data-collection time points, outcome measures, statistical analysis, and major findings (ie, longitudinal changes in prevalence, severity, and associated factors). RESULTS: Forty articles published between 2004 and 2019 were retained: 21 examined chemotherapy-treated patients only, and 19 employed control groups. Findings were mixed, with slightly more studies supporting the impact of chemotherapy on SCI. SCI tended to be more prevalent and severe after initiating chemotherapy, compared with patients' own baseline and controls not treated with chemotherapy. Impact appeared to be acute and more likely limited to subsamples. Most studies examining non-breast-cancer samples reported the lack or limited impact of chemotherapy on SCI. The most consistent moderators were depression and fatigue. Methodological issues regarding sampling design, measurement, and statistical analysis were discussed. CONCLUSION: More rigorously designed longitudinal studies would clarify direct and indirect effects of chemotherapy on SCI.

Efficacy of olanzapine, neurokinin-1 receptor antagonists, and thalidomide in combination with palonosetron plus dexamethasone in preventing highly emetogenic chemotherapy-induced nausea and vomiting: a Bayesian network meta-analysis.

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.

The association of BRCA1 and BRCA2 mutations with prostate cancer risk, frequency, and mortality: A meta-analysis.

BACKGROUND: A prior meta-analysis found no association between BRCA1 mutation and prostate cancer (PCa). Subsequent BRCA2 mutation studies have shown an association with PCa risk and mortality. We conducted a meta-analysis of overall BRCA mutation carriers and in subgroups to (1) estimate PCa risk in BRCA mutation carriers, (2) evaluate the frequency of BRCA mutation carriers in patients with PCa, and (3) compare cancer-specific survival (CSS) and overall survival (OS) among BRCA mutation carriers and noncarriers. METHODS: We searched the PubMed/MEDLINE, Embase, and Cochrane databases. Unadjusted odds ratio (OR), percentage (%), and hazard ratio (HR) were used to calculate pooled estimates for PCa risk, frequency, and survival, respectively. Subgroup analyses by mutation type ( BRCA1 or BRCA2) were conducted for the three objectives. Further subgroup analyses by study design (age-sex-adjusted or crude), ascertainment method (ascertained or inferred genotyping), population (Ashkenazi Jewish or general population), and survival outcomes (CSS or OS) were conducted. The associations were evaluated using random-effects models, in two-sided statistical tests. RESULTS: A total of 8 cohort, 7 case-control, 4 case-series, 28 frequency, and 11 survival studies were included. Being a BRCA mutation carrier ( BRCA1 and/or BRCA2) was associated with a significant increase in PCa risk (OR = 1.90, 95% CI = 1.58-2.29), with BRCA2 mutation being associated with a greater risk of PCa (OR = 2.64, 95% CI = 2.03-3.47) than BRCA1 (OR = 1.35, 95% CI = 1.03-1.76). The frequency of BRCA1 and BRCA2 carriers in patients with PCa was 0.9% and 2.2%, respectively. OS (HR = 2.21, 95% CI = 1.64-2.30) and CSS (HR = 2.63, 95% CI = 2.00-3.45) were significantly worse among BRCA2 carriers compared to noncarriers, whereas OS (HR = 0.47, 95% CI = 0.11-1.99) and CSS (HR = 1.07, 95% CI = 0.38-2.96) were statistically not significant when comparing BRCA1 carriers and noncarriers. CONCLUSIONS: There is a 1.90-fold greater risk of PCa in overall BRCA mutation carriers. This elevated PCa risk is attributable mainly to a 2.64-fold greater risk of PCa in BRCA2 carriers compared to a moderate 1.35-fold greater risk in BRCA1 carriers. The frequency of BRCA2 mutations was higher than BRCA1 mutations among patients with PCa. BRCA2 but not BRCA1 mutations were associated with higher PCa mortality. The BRCA mutation may be a clinical factor to stratify high-risk patients and guide clinical strategies for more effective treatments for patients with PCa.

Development of a biomarker mortality risk model in acute respiratory distress syndrome.

BACKGROUND: There is a compelling unmet medical need for biomarker-based models to risk-stratify patients with acute respiratory distress syndrome. Effective stratification would optimize participant selection for clinical trial enrollment by focusing on those most likely to benefit from new interventions. Our objective was to develop a prognostic, biomarker-based model for predicting mortality in adult patients with acute respiratory distress syndrome. METHODS: This is a secondary analysis using a cohort of 252 mechanically ventilated subjects with the diagnosis of acute respiratory distress syndrome. Survival to day 7 with both day 0 (first day of presentation) and day 7 sample availability was required. Blood was collected for biomarker measurements at first presentation to the intensive care unit and on the seventh day. Biomarkers included cytokine-chemokines, dual-functioning cytozymes, and vascular injury markers. Logistic regression, latent class analysis, and classification and regression tree analysis were used to identify the plasma biomarkers most predictive of 28-day ARDS mortality. RESULTS: From eight biologically relevant biomarker candidates, six demonstrated an enhanced capacity to predict mortality at day 0. Latent-class analysis identified two biomarker-based phenotypes. Phenotype A exhibited significantly higher plasma levels of angiopoietin-2, macrophage migration inhibitory factor, interleukin-8, interleukin-1 receptor antagonist, interleukin-6, and extracellular nicotinamide phosphoribosyltransferase (eNAMPT) compared to phenotype B. Mortality at 28 days was significantly higher for phenotype A compared to phenotype B (32% vs 19%, p = 0.04). CONCLUSIONS: An adult biomarker-based risk model reliably identifies ARDS subjects at risk of death within 28 days of hospitalization.