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Background: Pegfilgrastim is recommended to be administered at least 24 hours following the completion of chemotherapy, yet some clinicians use a same-day administration protocol. In this meta-analysis, we compared the incidence of chemotherapy-induced (febrile) neutropenia (CIN/FN) as well as CIN/FN-related chemotherapy disruptions in cancer patients provided with pegfilgrastim same-day vs. next-day. Methods: Six databases were searched for comparative studies of same-day vs. next-day pegfilgrastim administration. Fixed or random-effects meta-analyses were conducted to estimate pooled odds ratios (ORs) and 95% confidence intervals (CIs). Results: Thirteen studies were included in this meta-analysis. The FN OR for same-day vs. next-day administration was 1.48 (95% CI = 1.06–2.08) across all cycles, attributable mainly to studies of high FN risk (OR = 2.46, 95% CI = 1.04–5.83) vs. intermediate FN risk regimens (OR = 1.41, 95% CI = 0.95–2.10), and breast cancer (OR = 3.15, 95% CI = 1.24–8.01) vs. non-Hodgkin lymphoma (NHL; OR = 1.48, 95% CI = 0.98–2.23) and gynecologic cancers (OR = 0.64, 95% CI = 0.11–3.85). Where available, ORs for first cycle of chemotherapy, grades 3 and/or 4 CIN, and chemotherapy dose delays or reductions were in line with these findings. Conclusion: In this independent study, same-day pegfilgrastim administration may or may not increase the likelihood of FN, grades 3 and/or 4 CIN, and chemotherapy dose reductions or delays; and this may be a function of the myelotoxicity of the regimens (elevated in high-risk but not intermediate-risk regimens) and tumor type (elevated in breast but not in NHL or gynecologic cancers). With due caution, same-day pegfilgrastim administration may be safe and beneficial in intermediate-risk regimens and selected tumor types.

This commentary remarks on the recently published article by Qian et al on variations in market share of cancer treatments over time.

STUDY DESIGN: A meta-analysis of 89 randomized prospective, prospective, and retrospective studies on spinal endoscopic surgery outcomes. OBJECTIVE: The study aimed to provide familiar Oswestry Disability Index (ODI), visual analog scale (VAS) back, and VAS leg effect size (ES) data following endoscopic decompression for sciatica-type back and leg pain due to lumbar herniated disc, foraminal, or lateral recess spinal stenosis. BACKGROUND: Higher-grade objective clinical outcome ES data are more suitable than lower-grade clinical evidence, including cross-sectional retrospective study outcomes or expert opinion to underpin the ongoing debate on whether or not to replace some of the traditional open and with other forms of minimally invasive spinal decompression surgeries such as the endoscopic technique. METHODS: A systematic search of PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials from 1 January 2000 to 31 December 2019 identified 89 eligible studies on lumbar endoscopic decompression surgery enrolling 23,290 patient samples using the ODI and VAS for back and leg pain used for the ES calculation. RESULTS: There was an overall mean overall reduction of ODI of 46.25 (SD 6.10), VAS back decrease of 3.29 (SD 0.65), and VAS leg reduction of 5.77 (SD 0.66), respectively. Reference tables of familiar ODI, VAS back, and VAS leg show no significant impact of study design, follow-up, or patients’ age on ES observed with these outcome instruments. There was no correlation of ES with long-term follow-up (P = 0.091). Spinal endoscopy produced an overall ODI ES of 0.92 extrapolated from 81 studies totaling 12,710 patient samples. Provided study comparisons to tubular retractor microdiscectomy and open laminectomy showed an ODI ES of 0.9 (2895 patients pooled from 16 studies) and 0.93 (1188 patients pooled from 5 studies). The corresponding VAS leg ES were 0.92 (12,631 endoscopy patients pooled from 81 studies), 0.92 (2348 microdiscectomy patients pooled from 15 studies), and 0.89 (1188 open laminectomy patients pooled from 5 studies). CONCLUSION: Successful clinical outcomes can be achieved with various lumbar surgeries. ESs with endoscopic spinal surgery are on par with those found with open laminectomy and microsurgical decompression. CLINICAL RELEVANCE: This article is a meta-analysis on the benefit overlap between lumbar endoscopy, microsurgical decompression, laminectomy, and lumbar decompression fusion. LEVEL OF EVIDENCE: 2.

STUDY DESIGN: A design-agnostic standardized effect meta-analysis of 48 randomized, prospective, and retrospective studies on clinical outcomes with spinal endoscopic and interspinous process spacer (IPS) surgery. OBJECTIVE: The study aimed to provide reference set of Oswestry Disability Index (ODI) and visual analog scale (VAS) effect size data for back and leg pain following endoscopic and IPS decompression for lumbar herniated disc, foraminal, or lateral recess spinal stenosis. BACKGROUND: Mechanical low back pain following endoscopic transforaminal decompression may be more reliably reduced by simultaneous posterior column stabilization with IPS. METHODS: A systematic search of the PubMed, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials from 1 January 2000 to 2 April 2020, identified 880 eligible endoscopy and 362 IPS studies varying in design and metrics. The authors compared calculated standardized effect sizes (Cohen’s d) for extracted ODI, VAS-back, and VAS-leg data. RESULTS: The pooled standardized effect size combining the ODI, VAS-back, and VAS-leg data for the total sample of 19862 data sets from the 30 endoscopy and 18 IPS was 0.877 (95% CI = 0.857–0.898). When stratified by surgery, the combined effect sizes were 0.877 (95% CI = 0.849–0.905) for endoscopic decompression and 0.863 (95% CI = 0.796–0.930; P = 0.056) for IPS implantation. The ODI effect sizes calculated on 6462 samples with directly visualized endoscopic decompression were 0.917 (95% CI = 0.891–0.943) versus 0.798 (95% CI = 0.713–0.883; P < 0.001) with indirect IPS decompression (P < 0.001). The VAS-back effect sizes calculated on 3672 samples were 0.661 (95% CI = 0.585–0.738) for endoscopy and 0.784 (95% CI: 0.644–0.923; P = 0.187) for IPS. The VAS-leg effect sizes calculated on 7890 samples were 0.885 (95% CI = 0.852–0.917) for endoscopic decompression and 0.851 (95% CI = 0.767–0.935; P = 0.427). CONCLUSION: Lumbar IPS implantation produces larger reduction in low back pain than spinal endoscopy. On the basis of this meta-analysis, the combination of lumbar transforaminal endoscopy with simultaneous IPS has merits and should be formally investigated in higher grade clinical studies. CLINICAL RELEVANCE: Meta-analysis on the added clinical benefit of combining lumbar endoscopic decompression with an interspinous process spacer. LEVEL OF EVIDENCE: 2.

Background The treatment of osteoarticular infections in pediatric patients with sickle cell disease (SCD) is a challenging task for the practitioner. The aim of this study is to evaluate cefixime for the treatment of osteoarticular infections in pediatric SCD patients by retrospective design. Methods This study was done in the pediatric hospital of King Saud Medical City, Riyadh, Saudi Arabia. The data was obtained from medical records of patients aged 1-16 years admitted between January 2019 to December 2020, diagnosed with SCD and received cefixime for the treatment of OI. A descriptive study for pediatric patients admitted between January 2019 to December 2020 diagnosed with sickle cell disease and diagnosed with osteoarticular infection. All patients were treated with cefixime. Medians and interquartile ranges (IQRs) were used for the descriptive analysis. Results A total of 260 patients were screened, and 51 cases [osteomyelitis (OM), n = 43, and septic arthritis (SA), n = 8] met the inclusion criteria. The median age of OM patients was 7 years, with males making up 67.4% of the cohort. The median length of IV antibiotics and hospital stays were 10 days and 11 days, respectively. The median total duration of antibiotic use was 37 and 25 days for OM and SA, respectively. The treatment success rate was 88% in OM cases and 100% in SA patients. Readmission was noted in 39.5% of the OM patients, while only 25% of the SA patients were recorded for reinfection. Conclusion The study's findings revealed that Cefixime is a viable oral alternative for treating osteoarticular infection in pediatric SCD patients. Nonetheless, a prospective investigation is required to corroborate the findings of this study.

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.

This study aimed to estimate the incremental lifetime effects, costs, and net monetary benefit (NMB) of knowing BRCA information for recurrent ovarian cancer (ROC) patients in a given year and the cumulative savings of yearly hypothetical cohort testing over 16 years. We compared two strategies: (1) ‘with BRCA information’ and (2) ‘without BRCA information.’ Incremental NMB (INMB) was calculated as the average net monetized benefit of knowing BRCA status. The net monetized value (cumulative INMB) of knowing BRCA information was estimated by multiplying the INMB with the eligible ROC patients in year 2020 and extended for potential ROC patients over 16 yearly hypothetical cohorts of ROC patients Knowing BRCA information for ROC patients provided an additional monetized value of $3,528 in (payer) and $3,194 (society). Escalated to all ROC patients in the U.S. and future incidence ROC estimates, knowing BRCA information resulted in a lifetime cumulative INMB of $35.6 million (payer) and $32.2 million (society) for the 2020 cohort; and yielded an accumulated value of $97.3 million (payer) and $88.0 million (society) over 16 yearly hypothetical cohorts of ROC patients The economic value of knowing BRCA status of all U.S. ROC patients provides short-term and long-term evidence for optimizing treatment

This study aimed to estimate the incremental lifetime effects, costs, and net monetary benefit (NMB) of knowing BRCA information by universal genetic testing of all US women without breast cancer turning 40 in a given year, and the cumulative savings or losses of yearly cohort testing over 16 years. We compared two strategies: (1) ‘with BRCA information’ and (2) ‘without BRCA information.’ Incremental NMB (INMB) was calculated as the monetized benefit per person of knowing BRCA status. The net monetized value (cumulated INMB) of knowing BRCA information was estimated by multiplying the INMB with the eligible population or the year 2020 cohort of US women age 40 and extended for a total of 16 yearly cohorts. Universal testing of the female population at the age of 40 in a given year provided aan INMB of $663/person (payer) and $1,006/person (society).Escalated to the U.S. population of women age 40 , knowing BRCA status resulted in lifetime cumulated INMB of $1.3 billion (payer) and $2.0 billion (society) for the 2020 cohort; and yielded accumulated monetized value of $18.3 billion (payer) and $27.6 billion (society) over 16 yearly cohorts of 40-year-old women. The universal testing for BRCA status of all US women at age 40 provides compelling short-term and long-term economic value.

With the increasing occurrence of infectious diseases in lower-and-middle-income countries (LMICs), emergency preparedness is essential for rapid response and mitigation. Economic evaluations of mitigation technologies and strategies have been recommended for inclusion in emergency preparedness plans. We aimed to perform an economic evaluation using dynamic transition modeling of ebola virus disease (EVD) vaccination in a hypothetical community of 1,000 persons in the Democratic Republic of Congo (DRC).Using a modified SEIR (Susceptible, Exposed, Infectious, Recovered, with Death added [SEIR-D]) model that accounted for death and epidemiological data from an EVD outbreak in the DRC, we modeled the transmission of EVD in a hypothetical population of 1,000. With our model, we estimated the cost-effectiveness of an EVD vaccine and an EVD vaccination intervention.The results showed vaccinating 50% of the population at risk prevented 670 cases, 538 deaths, and 22,022 disability-adjusted life years (DALYs). The vaccine was found to be cost-effective with an incremental cost-effectiveness ratio (ICER) of $95.63 per DALY averted. We also determined the minimum required vaccination coverage for cost-effectiveness to be 40%. Sensitivity analysis showed our model to be fairly robust, assuring relatively consistent results even with variations in such input parameters as cost of screening, as well as transmission, infection, incubation, and case fatality rates.EVD vaccination in our hypothetical population was found to be cost-effective from the payer perspective. Our model presents an efficient and reliable approach for conducting economic evaluations of infectious disease interventions as part of an emergency preparedness plan.PLAIN LANGUAGE SUMMARYInfectious diseases affect lower-and-middle-income (LMIC) countries, with their limited resources, disproportionately more. This is certainly the case for ebola virus disease (EVD), a rare, severe, and mostly fatal disease. Vaccination is now available, but whether it is cost-effective remains an open question. We evaluated its cost-effectiveness by modeling the spread of EVD in a hypothetical population of 1000 persons. Using data from an EVD outbreak in the Democratic Republic of Congo (DRC), we estimated how many of persons susceptible to infection were exposed to the virus, became infected, recovered, or died. We did so for two scenarios: vaccinating versus not vaccinating enough people to achieve herd immunity. We assumed vaccinating 50% of the people and estimated how many infections, deaths, and disability-adjusted life years (DALY; the loss of the equivalent of a year of full health) would be prevented by vaccination. Our cost-effectiveness metric was the incremental cost of preventing one DALY.The outcomes of vaccination offset the additional costs. Vaccinating 50% of the population of 1000 cost an additional $2,081,358 but prevented 670 infections, 538 deaths, and 22022 DALYs. Preventing one DALY cost $95.63. This is very cost-effective as it is less than the gross domestic product (GDP) per capita for the DRC of $556.81. Vaccination below 40% of the population was less cost-effective, was most cost-effective at the herd immunity threshold of 45.3%, beyond which there were diminishing returns. Summarized, vaccination against EVD is clinically very effective and certainly worth the additional cost.

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.

PLAIN LANGUAGE SUMMARYYour physician, pharmacist, nurse, or even you can voluntarily report suspected adverse events associated with drugs. The FDA Adverse Reporting System (FAERS) and the WHO Vigibase are large databases that store individual reports of adverse drug reactions (ADRs). While some ADRs are very common, others are seen rarely. Detecting rare and very rare ADRs is extremely difficult but very important for the safe use of drugs. Databases such as FAERS and WHO Vigibase contain a large amount of data and are commonly used for analysis applying a statistical method called disproportionately analysis. This type of analysis determines whether there is a higher-than-expected number of adverse reactions for a particular drug. In the future, machine learning will complement this process by applying algorithms to the data, constructing and refining rules of inference, and building predictive models of ADRs. This paradigm change in testing for ADRs is expected to provide a better understanding of the factors impacting drug safety.

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.

Background The uncertainty about COVID-19 outcomes in angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB) users continues with contradictory findings. This study aimed to determine the effect of ACEI/ARB use in patients with severe COVID-19. Methods This retrospective cohort study was done in two Saudi public specialty hospitals designated as COVID-19 referral facilities. We included 354 patients with a confirmed diagnosis of COVID-19 between April and June 2020, of which 146 were ACEI/ARB users and 208 were non-ACEI/ARB users. Controlling for confounders, we conducted multivariate logistic regression and sensitivity analyses using propensity score matching (PSM) and Inverse propensity score weighting (IPSW) for high-risk patient subsets. Results Compared to non-ACEI/ARB users, ACEI/ARB users had an eight-fold higher risk of developing critical or severe COVID-19 (OR = 8.25, 95%CI = 3.32–20.53); a nearly 7-fold higher risk of intensive care unit (ICU) admission (OR = 6.76, 95%CI = 2.88–15.89) and a nearly 5-fold higher risk of requiring noninvasive ventilation (OR = 4.77,95%CI = 2.15–10.55). Patients with diabetes, hypertension, and/or renal disease had a five-fold higher risk of severe COVID-19 disease (OR = 5.40,95%CI = 2.0−14.54]. These results were confirmed in the PSM and IPSW analyses. Conclusion In general, but especially among patients with hypertension, diabetes, and/or renal disease, ACEI/ARB use is associated with a significantly higher risk of severe or critical COVID-19 disease, and ICU care.

PurposeCost-avoidance studies are common in pharmacy practice literature. This scoping review summarizes, critiques, and identifies current limitations of the methods that have been used to determine cost avoidance associated with pharmacists’ interventions in acute care settings.MethodsAn Embase and MEDLINE search was conducted to identify studies that estimated cost avoidance from pharmacist interventions in acute care settings. We included studies with human participants and articles published in English from July 2010 to January 2021, with the intent of summarizing the evidence most relevant to contemporary practice.ResultsThe database search retrieved 129 articles, of which 39 were included. Among these publications, less than half (18 of 39) mentioned whether the researchers assigned a probability for the occurrence of a harmful consequence in the absence of an intervention; thus, a 100% probability of a harmful consequence was assumed. Eleven of the 39 articles identified the specific harm that would occur in the absence of intervention. No clear methods of estimating cost avoidance could be identified for 7 studies. Among all 39 included articles, only 1 attributed both a probability to the potential harm and identified the cost specific to that harm.ConclusionCost-avoidance studies of pharmacists’ interventions in acute care settings over the last decade have common flaws and provide estimates that are likely to be inflated. There is a need for guidance on consistent methodology for such investigations for reporting of results and to confirm the validity of their economic implications.

Androgen deprivation therapy (ADT) for prostate cancer is associated with adverse effects, such as obesity and metabolic syndrome, which increase cardiovascular risk, the most common cause of non-cancer mortality in men diagnosed with prostate cancer. The Comprehensive Lifestyle Improvement Program for Prostate Cancer (CLIPP) was created to determine the feasibility of conducing a comprehensive lifestyle modification intervention in men on ADT for prostate cancer and determine its early efficacy in reducing obesity and metabolic syndrome. A single-arm, open-label clinical trial was conducted by recruiting 31 men diagnosed with prostate cancer and exposed to ADT within the last 5 years. A multicomponent lifestyle modification program was delivered weekly for 16 weeks by a trained health coach. This was followed by 8 weeks of passive follow-up resulting in a total trial duration of 24 weeks. Feasibility was determined by calculating study recruitment, retention, and adherence rates. Weight and components of metabolic syndrome (waist circumference, triglycerides (TG), high-density lipoprotein (HDL), serum glucose, and blood pressure (BP)) were measured at baseline, 12, and 24 weeks. Recruitment, retention, and adherence rates were 47.1%, 90.3%, and 100%, respectively. Statistically significant improvements were noted between baseline and end of study measurements for weight (206.3 vs. 191.3 lbs, p

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 9/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.

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.

Melanoma in Black patients carries a poor prognosis. Due to its rarity, melanoma in this population has not been well characterized. This study evaluates survival predictors in Black patients with melanoma. This was a retrospective cohort study of Black patients with cutaneous melanoma from the National Cancer Database 2004-2018. Of the 2464 cases, melanoma was more common among females than males (57.1% vs. 42.9%, p .001). Median Breslow depth was 1.8 mm (interquartile range 0.4-4.4). Lower extremities were the most common location (52.8%), followed by upper extremities (13.1%) along with otherwise specified/overlapping/other (13.1%), then by trunk (11.8%), and lastly head and neck (9.2%). Stage at diagnosis was I (30.7%), II (27.5%), III (24.1%), and IV (17.7%). Ulceration was observed in 41.4% of lesions. Acral lentiginous melanoma (ALM) was the most common specific histologic subtype (20.3%), followed by superficial spreading melanoma (9.4%). After adjusting for confounders, higher stages and primary site on the head and neck were the strongest independent predictors of worse overall survival. Melanoma in Black patients is most likely to appear on the lower extremities. A large portion (41.8%) presented with stage III or IV disease. ALM was the most common specific histologic subtype.

Seven prospective real-world studies conducted in general practices in Belgium of antihypertensive treatment with valsartan-centric regimens were pooled to examine similarities and differences in determinants of blood pressure (BP) values (mmHg) and BP control rates between female and male patients.Pooled analysis of a total evaluable sample of 17,044 patients, including 8273 (48.5%) women and 8771 men (51.5%) treated over approximately 90 days with valsartan-centric regimens in second or later line. Hierarchical linear and logistic regressions were applied to identify patient- and physician-related determinants of BP outcomes and a potential physician class effect.Reductions in BP (mmHg) over 90 days were similar for women and men, and so were changes in BP control rates. Approximately a quarter of the variance in 90 day BP values was attributable to a physician class effect. Both gender groups shared some patient- and physician-related determinants of BP outcomes, though often varying in degree of influence. Analyses also revealed gender-specific determinants. Among others, modifiable/manageable patient-related determinants included BP at hypertension diagnosis (proxy for time of diagnosis), risk factors, antihypertensive treatment and adherence; while among the physician-related determinants clinical experience in hypertension treatment was modifiable/manageable.Valsartan-centric treatment regimens are associated with significant reductions in BP level and improvement in BP control in both women and men. The determinants revealed in modeling provide guidance to clinicians in the common and differential management of hypertension in female and male patients.

Therapeutic guidelines recommend prophylaxis against chemotherapy-induced (febrile) neutropenia (CIN/FN). Pegfilgrastim (Neulasta), biosimilar pegfilgrastim-jmdb (Fulphila), and pegfilgrastim with on-body injector (OBI; Neulasta Onpro) are options for CIN/FN prophylaxis. We aimed to simulate the cost-savings and budget-neutral expanded access to CIN/FN prophylaxis or anticancer treatment achieved through conversion from pegfilgrastim-OBI to pegfilgrastim-jmdb and to evaluate the economic impact of FN-related hospitalization costs due to pegfilgrastim-OBI failure.Cost-savings from conversion from pegfilgrastim-OBI to biosimilar pegfilgrastim-jmdb were simulated in a panel of 15,000 patients with cancer from the US payer perspective. The primary analyses included conversion rates of 10% to 100%. Adjusted analyses also considered OBI device failure rates of 1% to 7% and associated costs of FN-related hospitalization. Simulations of budget-neutral expanded access to prophylaxis with pegfilgrastim-jmdb or to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for diffuse large B-cell lymphoma (DLBCL) were also performed.In a 15,000-patient panel, conversion from pegfilgrastim-OBI to pegfilgrastim-jmdb resulted in cost-savings ranging from $481,259 (10% conversion) to $4,812,585 (100% conversion) in a single cycle. Over 6 cycles at 100% conversion, savings were $28,857,510 and could provide 9,191 additional doses of pegfilgrastim-jmdb or 4,463 cycles of R-CHOP to patients with DLBCL. Adjusted for OBI failure, cost-savings over 6 cycles ranged from $2,935,565 (10% conversion; pegfilgrastim-OBI failure rate of 1%) to $32,236,499 (100% conversion; 7% failure). These cost-savings could provide 943 doses of pegfilgrastim-jmdb or 454 doses of R-CHOP (10% conversion; 1% pegfilgrastim-OBI failure) or provide 10,261 doses of pegfilgrastim-jmdb or 4,982 cycles of R-CHOP (100% conversion; 7% failure).Conversion from pegfilgrastim to pegfilgrastim-jmdb is associated with significant cost-savings which increase markedly when also accounting for pegfilgrastim-OBI failure and associated FN-related hospitalizations. These general and failure-related cost-savings could be allocated on a budget-neutral basis to provide more patients with additional CIN/FN prophylaxis or antineoplastic treatment.

Aim Evaluate long-term real-world treatment patterns and associated effectiveness and safety outcomes in patients with diabetic macular edema (DME) treated ≥36 months with 0.5mg ranibizumab. Methods Open-label observational effectiveness study in 9 Belgian clinics. Included were primary treated eyes of 55 DME patients between August 2014 and March 2015 and followed for 3.5±1.8 years. Eyes were 21.8% treatment (TX)-naive, 9.1% non-naive with exclusive prior anti-VEGF treatment (PRIOR-anti-VEGF), and 63.6% non-naive with other prior treatments (PRIOR-other). Intravitreal injections with ranibizumab were administered per ophthalmologists' best clinical judgment. Trend testing of changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) over time occurred using mixed regression analysis. Results The mean±SD number of treatments in the first year was 5.1±3.0 (TX-naive), 4.5±2.7 (PRIOR-anti-VEGF) and 5.6±3.1 (PRIOR-other). At 12 months, BCVA increased by 8.9±16.4 letters from 59.7±9.3 at baseline in TX-naive (p

In this pharmacoeconomic simulation, we: (1) modeled the cost-efficiency of converting patients from reference pegfilgrastim to biosimilar pegfilgrastim-cbqv for prophylaxis of chemotherapy-induced (febrile) neutropenia (CIN/FN) from the US payer perspective, (2) simulated how savings enable, on a budget-neutral basis, expanded access to pegfilgrastim-cbqv, and (3) estimated the number-needed-to-convert (NNC) to purchase one additional dose of pegfilgrastim-cbqv.In a hypothetical panel of 20,000 patients, we modeled cost-savings utilizing: two reference formulations (pre-filled syringe [PFS] and on-body injector [OBI]), three medication cost inputs (average sales price [ASP], wholesale acquisition cost [WAC], and an age-proportionate blended ASP/WAC rate), administration cost for injection (PFS) and device application (OBI), conversion rates of 10-100%, and 1-6 cycles of prophylaxis. Cost-savings were used to estimate additional doses of pegfilgrastim-cbqv that could be purchased and the NNC to purchase one additional dose.Using ASP and 10% conversion from reference OBI to pegfilgrastim-cbqv, savings range from $326,744 (1 cycle) to $2.0M (6 cycles) which could provide 93-556 additional doses of pegfilgrastim-cbqv, respectively; the NNC to purchase one additional dose of pegfilgrastim-cbqv ranges from 21.6 (1 cycle) down to 3.6 patients (6 cycles). The WAC model saves $41.1M per cycle and $246.7M over 6 cycles at 100% conversion from reference PFS which could provide 9,709-58,253 additional pegfilgrastim-cbqv doses; the NNC ranges from 2.1 (1 cycle) to 0.3 (6 cycles). Using the blended ASP/WAC rate, converting 50% from reference OBI to pegfilgrastim-cbqv would save $10.2M per cycle and $60.9M over 6 cycles providing 2,638-15,829 additional doses of pegfilgrastim-cbqv; NNCs are 3.8 (1 cycle) and 0.6 patients (6 cycles).Converting 20,000 patients from reference to pegfilgrastim-cbqv over 6 cycles can generate savings up to $246.7M, enough to purchase up to 58,253 additional doses of pegfilgrastim-cbqv. This simulation provides economic justification for prophylaxis with biosimilar pegfilgrastim-cbqv.

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.

This study examined whether (a) cancer patients in two cohorts reported greater subjective cognitive impairment (SCI) in prevalence and severity than noncancer healthy controls; and (b) selected psychoneurological factors (fatigue, stress, and sleep disturbance) contribute to such differences. Data from 60 prechemotherapy cancer patients, 81 active-chemotherapy cancer patients, and 116 noncancer healthy controls were analyzed using hierarchical regressions. The prevalence rate of SCI was higher in the prechemotherapy cancer cohort (41.6%) and in the active-chemotherapy cancer cohort (46.9%) than in healthy controls (21.5%; p

Six Delta is a six-dimensional independent platform for outcome-based pricing/contracting. The sixth dimension (δ6) estimates prices on the basis of adherence to the prescribed regimen, whereby man...

Six Delta is a six-dimensional independent platform for outcome-based pricing/contracting. The second dimension (δ2) estimates prices on the basis of four willingness-to-pay (WTP) thresholds. We de...