Cost-effectiveness of intravenous resuscitation fluids in sepsis patients: a patient-level data analysis in Jordan.

AIM: Albumin role as fluid resuscitation in sepsis remains understudied in low- and middle-income countries. This study aimed to evaluate the cost-effectiveness of intravenous (IV) Albumin compared to Crystalloids in sepsis patients using patient-level data in Jordan. METHODS: This was a retrospective cohort study of sepsis patients aged 18 or older admitted to intensive care units (ICU) at two major tertiary hospitals during the period 2018-2019. Patients information, type of IV fluid, and clinical outcomes were retrieved from medical records, and charges were retrieved from the billing system. A 90-day partitioned survival model with two health states (alive and dead) was constructed to estimate the survival of sepsis patients receiving either Albumin or Crystalloids as IV fluids for resuscitation. Overall survival was predicted by fitting a Weibull model on the patient-level data from the current study. To further validate the results, and to support the assessment of uncertainty, time-dependent transition probabilities of death at each cycle were estimated and used to construct a state-transition patient-level simulation model with 10,000 microsimulation trials. Adopting the healthcare system perspective, incremental cost-effectiveness ratios(ICERs) of Albumin versus Crystalloids were calculated in terms of the probability to be discharged alive from the ICU. Uncertainty was explored using probabilistic sensitivity analysis. RESULTS: In the partitioned survival model, Albumin was associated with an incremental cost of $1,007 per incremental1% in the probability of being discharged alive from the ICU. In the state-transition patient-level simulation model, ICER was $1,268 per incremental 1% in the probability of being discharged alive. Probabilistic sensitivity analysis showed that Albumin was favored at thresholds >$800 per incremental 1%in the probability of being discharged alive from the ICU. CONCLUSION: IV Albumin use in sepsis patients might not be cost-effective from the healthcare perspective of Jordan. This has important implications for policymakers to readdress Albumin prescribing practice in sepsis patients.

Sepsis is a life-threatening complication of infection, which usually requires resuscitation with intravenous fluids. Still, no conclusive evidence is available about the best fluid resuscitation to be used in sepsis patients especially in low- and middle-income countries. This study compared the costs and effectiveness of intravenous Albumin versus Crystalloids in sepsis patients. Findings from this study showed that resuscitation with Albumin is much more expensive compared to resuscitation with Crystalloids with no significant difference in mortality but with prolonged length of stay in the hospital and the intensive care unit. Decision makers are advised to change Albumin prescribing practices in a way that mitigates the associated clinical and financial burdens without compromising quality of care or resuscitate with Crystalloids.

ALBUMIN VERSUS STANDARD MEDICAL TREATMENT IN BRAZILIAN PUBLIC AND PRIVATE HEALTHCARE SYSTEMS.

•To assess the economic impact of implementing long-term albumin infusions in patients with cirrhosis and ascites in Brazil •Incremental cost per cirrhotic patient treated with long-term albumin was estimated based on the rates of complications and healthcare resource utilization from the ANSWER trial and local costs from the public and private healthcare system perspective in Brazil. •Implementation of long-term albumin could save up to 118,759 BRL and 189,675 BRL per patient treated in the public and private healthcare system setting, respectively. •Should results from the ANSWER trial translate into real-world effectiveness, addition of albumin to standard medical treatment could lead to improved clinical outcomes and reduced costs. Background - Cirrhosis is one of the final stages of chronic liver disease. Common causes of cirrhosis include alcoholism and viral hepatitis infections. Cirrhosis can progress from an asymptomatic, compensated phase to decompensation and the appearance of overt symptoms. There is no specific treatment for decompensated cirrhosis. The ANSWER trial positioned long-term albumin infusions as a potential treatment for patients with cirrhosis and uncomplicated ascites. Objective - This study assesses the economic impact of albumin infusions following the ANSWER trial regimen in Brazilian patients with decompensated cirrhosis from the public and private healthcare systems perspectives. Methods - The incremental cost per patient per year was calculated for standard medical treatment (SMT) plus long-term albumin infusions versus SMT alone. Costs of diuretics and albumin were obtained from Banco de Preços em Saúde and the Drug Market Regulation Chamber. Costs for complication and procedures were gathered from the published literature. Costs were transformed to 2021 Brazilian reals (BRL). Incidences of clinical complications and treatments were gathered from the ANSWER trial. Univariate sensitivity analysis was performed by increasing and decreasing all inputs by 20%. Results - The cost per patient per year was 118,759 BRL and 189,675 BRL lower for patients treated with SMT and albumin (compared to SMT only) for the public and private healthcare systems, respectively. The additional cost of albumin was offset by reduced complications and treatments (149,526 BRL and 249,572 BRL, respectively). The univariate sensitivity analysis showed cost savings for both healthcare systems in all the scenarios assessed. Conclusion - This economic analysis suggests that, if the ANSWER trial clinical outcomes translate into real-world effectiveness, addition of albumin infusions to SMT in patients with decompensated cirrhosis may lead to cost savings for the public and private healthcare systems in Brazil.

Treatment-Related Cost Analysis of Terlipressin for Adults with Hepatorenal Syndrome with Rapid Reduction in Kidney Function.

INTRODUCTION: Hepatorenal syndrome (HRS), a special form of acute kidney failure, is a rare, acute, life-threatening complication of cirrhosis and has a very poor prognosis. Terlipressin (TERLIVAZ®) is the first and only pharmacological treatment approved by Food and Drug Administration (September 2022) to improve kidney function for adults with HRS with rapid reduction in kidney function. We constructed a decision analytic economic model to estimate the cost per complete response/HRS reversal of terlipressin + albumin from a United States hospital perspective. METHODS: A decision analytic model was developed to estimate the HRS treatment-related cost per response over an HRS hospitalization (assuming 14 days). Patients can experience either HRS reversal (complete response) or no HRS reversal (partial/no response) upon receipt of treatment. The efficacy, safety, and treatment duration data were from published head-to-head randomized international trials. Total treatment cost comprised drug acquisition and treatment-related costs (intensive care unit [ICU], dialysis [intermittent or continuous], pulse oximetry monitoring for terlipressin, and adverse events) sourced from the published literature. Cost per response, defined as the total treatment cost per HRS reversal was estimated for each treatment. The number needed to treat (NNT), defined as the number of patients treated to achieve HRS reversal in 1 additional patient, was estimated. RESULTS: Cost per response of terlipressin + albumin was lower than midodrine and octreotide + albumin (M&O) (US$85,315 vs. $467,794) and norepinephrine + albumin ($81,614 vs. $139,324). NNT for HRS reversal was 2 patients with terlipressin + albumin vs. M&O + albumin and 4 patients with terlipressin + albumin vs. norepinephrine + albumin, respectively. CONCLUSIONS: The analysis shows that terlipressin is a cost-effective treatment due to its higher efficacy and administration in the non-ICU setting. Terlipressin is a value-based treatment option for appropriate adults with HRS with rapid reduction in kidney function.

Hepatorenal syndrome, a functional, progressive kidney failure, is a life-threatening complication of cirrhosis. It is important to improve kidney function in patients who are hospitalized with hepatorenal syndrome considering the cost of treatment. This study assessed the cost per complete response/ hepatorenal syndrome reversal of terlipressin + albumin from a United States hospital perspective. This study shows that terlipressin improves kidney function with lower intensive care unit and dialysis costs compared with unapproved treatments. Terlipressin is a cost-effective, value-based treatment option for appropriate adults with hepatorenal syndrome with rapid reduction in kidney function.

Cost-effectiveness of terlipressin for hepatorenal syndrome: the United States hospital perspective.

BACKGROUND: Hepatorenal syndrome (HRS) is characterized by severely reduced renal perfusion that precipitates rapid morbidity and mortality. Terlipressin is the only US Food and Drug Administration-approved treatment to improve kidney function for adults with HRS with a rapid reduction in kidney function. Prior to the approval of terlipressin, unapproved vasoconstrictive agents used in HRS treatment were octreotide/midodrine and norepinephrine with albumin. METHODS: A cohort decision-tree model representing a US hospital perspective assessed the clinical outcomes and direct medical costs (based primarily on hospital charges) of treating HRS with terlipressin + albumin (ALB) versus midodrine/octreotide (MID/OCT)+ALB, or norepinephrine (NorEp)+ALB. Treatment efficacy was defined by clinical response (complete/HRS reversal, partial, or no response) based on change of serum creatinine derived from published clinical trial reports. The proportions of patients with complete response were: terlipressin + ALB (36.2%), NorEp + ALB (19.1%), and MID/OCT + ALB (3.1%). Model outcomes included utilization of HRS-related healthcare resources (hospital and intensive care, outpatient and emergency department, dialysis, and transplantations), adverse events, and HRS-related mortality. Outcomes were assessed for the initial hospitalization in the base case and at 30, 60, and 90 days post-discharge. RESULTS: Total costs incurred over the initial hospitalization with terlipressin + ALB were lower vs NorEp + ALB, primarily due to higher ICU costs with NorEp + ALB ($7,433 vs $61,897). TER + ALB was associated with higher total costs vs MID/OCT + ALB due to higher pharmacy costs with terlipressin + ALB. The cost per complete response achieved of terlipressin + ALB ($451,605) was half that of NorEp + ALB ($930,571) and one-tenth that of MID/OCT + ALB ($4,942,123). CONCLUSIONS: HRS patients treated with terlipressin experienced better clinical outcomes and a lower cost per treatment response vs other unapproved treatments. ICU days and pharmacy costs were key cost drivers distinguishing the treatment groups. These outcomes suggest that terlipressin is cost-effective on the basis of total cost per response achieved.

Hepatorenal syndrome (HRS) is a rare and sudden life-threatening complication of the liver. Patients with HRS should receive immediate treatment with a drug that narrows blood vessels known as a vasoconstrictor. Terlipressin is the most common vasoconstrictor used for patients with HRS. Other common vasoconstrictors are midodrine with octreotide and norepinephrine. This study aimed to compare the cost of terlipressin with those of midodrine with octreotide and norepinephrine while also considering how well each of them worked to reverse HRS. This was done using an economic model. This economic model assessed the costs of the vasoconstrictor drugs and the costs of treating HRS, including costs attributable to drug acquisition, adverse events, organ transplantation, dialysis, and institutional encounters (i.e. hospitalization, ICU, emergency department, and outpatient visits). The magnitude of these costs depends on how well each drug reversed HRS. Based on inputs derived from their respective clinical trials, 36% of patients who were given terlipressin had a complete response (HRS was reversed), 19% of patients who were given norepinephrine had a complete response, and 3% of patients who were given midodrine with octreotide had a complete response. The total cost per patient was approximately $163,481 for terlipressin, $177,298 for norepinephrine, and $155,030 for midodrine with octreotide. When the costs were evaluated against how well the drugs worked to reverse HRS, the lowest cost per HRS reversal was $451,605 when treated with terlipressin. The cost per reversal for norepinephrine was $930,571 and for midodrine with octreotide was $4,942,123. These results show that terlipressin works well and is more cost-effective for US hospitals compared with the other unapproved treatment options for HRS with rapid reduction in kidney function.

COST EFFECTIVENESS OF USING TERLIPRESSIN TO TREAT HEPATORENAL SYNDROME.

BACKGROUND: Hepatorenal syndrome (HRS) is the most severe form of acute kidney injury in patients with advanced cirrhosis, and it is associated with high mortality. It is usually diagnosed according to criteria defined by the International Ascites Club. Currently, the most frequently indicated pharmacological therapy for the treatment of HRS is a combination of splanchnic vasoconstrictors (terlipressin or norepinephrine) in combination with albumin. With the progressive increase in healthcare spending, it is important to conduct a cost-effectiveness analysis of pharmacological treatment in patients who are diagnosed with HRS. OBJECTIVE: To perform a cost-effectiveness assessment for the use of terlipressin in combination with albumin to treat HRS in patients with cirrhosis. METHODS: Economic evaluation of cost-effectiveness based on secondary data from studies showed the efficacy of terlipressin therapy compared with norepinephrine combined with albumin or albumin alone. The cost-effectiveness analysis was calculated using an incremental cost-effectiveness ratio (ICER), and a sensitivity analysis was developed by varying the values of therapies and probabilities. The Brazilian real was the currency used in the analysis, and the results were converted to US dollars. RESULTS: After selection, eligibility, and evaluation of the quality of publications, the results demonstrated that administration of terlipressin or norepinephrine in combination with albumin in patients diagnosed with HRS type 1 was efficacious. The cost of treatment with terlipressin in combination with albumin was USD $1,644.06, administration of albumin alone was USD $912.02, and norepinephrine plus albumin was USD $2,310.78. Considering that the combination therapies demonstrated effectiveness, the incremental cost of terlipressin and norepinephrine in combination with albumin was USD $666.73, and an effectiveness of 0.570 was found for terlipressin in combination with albumin and 0.200 for norepinephrine in combination with albumin. The incremental effectiveness was 0.370, and the ICER was USD $1,801.97. Thus, the parameters of increasing cost per therapy and ICER indicated that the combined therapy of terlipressin plus albumin was cost effective compared to albumin alone or norepinephrine plus albumin in a public single-payer healthcare system. CONCLUSION: A cost-effectiveness analysis showed that terlipressin in combination with albumin when administered concomitantly to patients who were diagnosed with type 1 HRS is cost-effective compared to norepinephrine in combination with albumin administered in a controlled environment.

Economic evaluation of long-term albumin use in cirrhosis patients from the Mexican healthcare system perspective.

INTRODUCTION AND OBJECTIVES: Liver cirrhosis is a major public health issue associated with high morbidity and mortality. The ANSWER trial showed that long-term human albumin (LTA) infusions led to significant reduction of complications and mortality in patients with uncomplicated ascites. The present study aimed to assess the incremental cost of cirrhosis patients treated with LTA plus standard medical treatment (SMT) versus those treated with SMT from the perspective of the Mexican Social Security Institute (IMSS). MATERIAL AND METHODS: Cost of illness for patients with cirrhosis and grade 2-3 ascites treated with SMT or with SMT and LTA (following the treatment regimen from ANSWER) over a one-year period was estimated according to the IMSS perspective. Rates of treatments, complications and hospitalizations were based on results from the ANSWER trial. Unit costs from IMSS were gathered from public sources and transformed to 2020 Mexican $ (Mex$). RESULTS: The use of LTA is estimated to require additional annual expenditure derived from the pharmacological cost of human albumin and by the follow up visits required for LTA administration (Mex$28,128). However, this cost may potentially be counterbalanced by the reduction in paracentesis, cirrhosis-related complications and hospitalizations which would lead to cost savings of Mex$33,417 per patient/year. CONCLUSIONS: Based on the ANSWER trial results, our study suggests that LTA may result in improved clinical outcomes and reduced costs for the IMSS when administered to cirrhosis patients with uncomplicated ascites.

Neglected geriatric assessment and overtreatment of older patients with pancreatic cancer - Results from a prospective phase IV clinical trial.

BACKGROUND: Older patients with metastatic pancreatic cancer may suffer increased toxicity from intensive chemotherapy. Treatment individualization by geriatric assessment (GA) might improve functional outcome. METHODS: We performed a multicenter, phase IV, open label trial in patients ≥70 years with metastatic pancreatic adenocarcinoma. Patients underwent GA and were assigned to one of three categories based on their scores: Go-Go, Slow-Go, or Frail. These categories were intended to guide physician's treatment decisions when choosing to treat patients with nab-paclitaxel/gemcitabine (arm A), gemcitabine (arm B), or best supportive care (arm C). Primary objective was a stable (loss of five points or less) Barthel's Activities of Daily Living (ADL) score during chemotherapy; secondary endpoints included GA scores during therapy, safety, quality of life, response and survival rates. RESULTS: Thirty-two patients were enrolled in the trial in six centers in Germany (out of 135 planned), resulting in termination due to low recruitment. Fifteen patients were allocated to nab-paclitaxel/gemcitabine, fifteen to gemcitabine, and two to best supportive care by their physicians, although according to their GA scores 29 patients (91%) were categorized as Slow-Go and three (9%) as Go-Go. Thus, fifteen of 32 (47%) patients were misclassified and given a course of treatment inconsistent with their GA scores. Median progression-free survival (PFS) were 3.3 months and 9.1 months and median time to quality-of-life deterioration 13 days and 29 days in the nab-paclitaxel/gemcitabine and gemcitabine monotherapy arms, respectively. Serious adverse events were reported in 11 (78.6%) patients in the nab-paclitaxel/gemcitabine and 8 (53.3%) patients in the gemcitabine arm. CONCLUSIONS: Clinical evaluations by investigators differed markedly from geriatric assessments, leading to potential overtreatment. In our modest sample size study, those patients undergoing more intensive therapy had a less favorable course.

Metastatic Pancreatic Cancer Second-Line Treatment Options: Is the Difference Only in Cost?

INTRODUCTION: Although pancreatic cancer ranks seventh in cancer-related deaths, it is an extremely fatal disease, and more than 330,000 people die from this disease worldwide. Although there are many first-line treatment studies in the literature, there are almost no prospective studies regarding second-line therapy. Therefore, there is no standard approach in the second-line treatment of pancreatic cancer. We decided to conduct this study to investigate second-line treatments with problems such as cost, treatment efficacy, and toxicity. METHODS: Patients older than 18 years old who applied to Ege University Hospital medical oncology department with a diagnosis of metastatic pancreatic cancer, who received first-line chemotherapy due to their illness, and who had progressed afterwards were included in the study. The files of the patients who applied between 2013 and 2017 were examined. RESULTS: Our study's primary endpoint was progression-free survival, and it was found that the median progression-free survival was 3.2 months in the Xelox patients, 3.7 months in the gemcitabine-nab paclitaxel patients, and 3.5 months in the other regimens. When the secondary endpoint was evaluated, overall survival, the median overall survival was 5.9 months in the Xelox patients, 5.3 months in the gemcitabine-nab paclitaxel patients, and 4.8 months in the other regimens. CONCLUSION: As a result, second-line treatments were compared, and no statistically significant difference was found between them. For this reason, the side effects of previously used drugs and the side effects of new drugs to be used, as well as their costs, should be evaluated when choosing a treatment.

Albumin for cirrhosis-related complications.

WHAT IS KNOWN AND OBJECTIVE: The purpose of this paper was to discuss the limitations of the studies serving as the evidence for recommendations in clinical practice guidelines concerning albumin use for cirrhosis-related complications, review relevant studies published since the guidelines and suggest directions for future investigations. COMMENT: There are no recent comprehensive clinical practice guidelines concerning albumin. Instead, more recent albumin guidelines reflect areas of specialty practice such as those by American and European associations for the study of the liver and liver disease. Studies published since the guidelines are useful for helping to define the most appropriate indications for albumin with respect to cirrhosis-related complications, as well as directions for future research. WHAT IS NEW AND CONCLUSION: Albumin has a long history of attempts to define appropriate uses by meta-analysis, but given the high cost and episodic shortages of albumin, there is a need for adequately powered randomized controlled trials using current state-of-the-art care evaluating the use of albumin to prevent or treat cirrhosis-related complications.

Clinical and economic burden of intravenous paclitaxel or nab-paclitaxel for metastatic breast cancer.

BACKGROUND: Intravenous (IV) taxane therapy for metastatic breast cancer (mBC) has been associated with toxicities and demanding dosing schedules, which can limit treatment effectiveness. OBJECTIVES: To assess treatment patterns, toxicities, and costs in women with mBC initiating IV paclitaxel or IV nab-paclitaxel. METHODS: Adult women diagnosed with BC from January 1, 2014, to September 30, 2018, were identified in the MarketScan Commercial and MarketScan Medicare Supplemental databases. Women had a metastatic disease diagnosis and newly initiated treatment with IV paclitaxel/nab-paclitaxel (first administration date was considered the index date), and continuous enrollment for at least 12 months prior to and at least 3 months following the index date. Treatment discontinuation, dose reductions, toxicities, and health care utilization and costs per patient per month (PPPM) were assessed over the full follow-up and the index line of IV paclitaxel/nab-paclitaxel therapy (Index LOT). RESULTS: The sample included 8890 women aged 54.6 (±10.9) years, followed for 18.9 (±13.5) months. Most (82.0%) initiated IV paclitaxel/nab-paclitaxel monotherapy; 83.1% had early discontinuation (<18 weeks of treatment) of the Index LOT. Among the 6943 women eligible for the dose-change analysis, 42.4% evidenced an IV paclitaxel/nab-paclitaxel dose reduction ≥10% during the Index LOT. The most common toxicities during the Index LOT were gastrointestinal upset (30.5%), myelotoxicity (27.0%), infection (26.2%), general symptoms (25.9%), and chemotherapy-induced peripheral neuropathy (22.7%). Over follow-up, 39.7% of women had an inpatient admission and 43.0% had an emergency department visit. The mean of all-cause total costs was $11,991 PPPM, while BC-related total costs were $5320 PPPM. CONCLUSIONS: Many mBC patients initiating IV paclitaxel/nab-paclitaxel experienced dose reductions, toxicities, and/or early discontinuation of the Index LOT, which may limit treatment effectiveness. More tolerable treatments with reduced dosing complexity could improve mBC treatment and help contain costs.

Chemotherapy-induced peripheral neuropathy in metastatic breast cancer patients initiating intravenous paclitaxel/nab-paclitaxel.

BACKGROUND: Intravenous (IV) taxanes for metastatic breast cancer (mBC) are associated with toxicities, such as chemotherapy-induced peripheral neuropathy (CIPN), which can detrimentally impact outcomes. OBJECTIVE: To assess the impact of CIPN on clinical and economic outcomes in women with mBC, initiating IV paclitaxel/ nab-paclitaxel. METHODS: Adult women in the MarketScan Commercial and Medicare Supplemental Database with a mBC diagnosis, initiating IV paclitaxel or IV nab-paclitaxel (index date = first administration) from November 1, 2013, to September 30, 2018, who had no prior neuropathy diagnoses, and continuous enrollment 12 months prior to and ≥ 3 months following index were selected. Propensity score-matched CIPN and non-CIPN cohorts were defined, based on postindex CIPN diagnosis. Clinical characteristics and all-cause and breast cancer (BC)-related health care utilization and costs per patient per month (PPPM) were compared between matched CIPN and non-CIPN cohorts during follow-up. RESULTS: Among the 5870 women with mBC initiating IV paclitaxel/nab-paclitaxel, 42.7% developed CIPN. The matched cohorts each included 1950 women. Patients with CIPN were more likely to have a dose reduction (46.1% vs 38.2%, P < .001) or develop depression, diabetes, insomnia, liver dysfunction, or arthritis compared with the non-CIPN cohort, P < .05. Patients with CIPN were more likely to have an inpatient admission (39.2% vs 34.9%, P < .01) or emergency department visit (46.7% vs 35.6%, P < .001), as well as all-cause and BC-related costs that were $1102 and $725 PPPM higher, respectively, than women without CIPN (P < .01). CONCLUSIONS: CIPN was common in women, following IV paclitaxel/nab-paclitaxel treatment and was associated with dose reductions, the development of comorbidities, and elevated health care costs. Therapies for mBC that offer increased tolerability are needed to help improve patient outcomes and control costs.

Clinical Pharmacist-Led Impact on Inappropriate Albumin Utilization and Associated Costs in General Ward Patients.

BACKGROUND: Inappropriate albumin use in clinical practice remains problematic. Health-systems face continued challenges in promoting cost-appropriate use. OBJECTIVE: To evaluate the clinical and economic impact of a clinical pharmacist-led intervention strategy targeting inappropriate albumin use in general ward patients. METHODS: A retrospective cohort study evaluated all adult (≥18 years) general ward patients administered ≥1 dose of albumin at a university medical center over a 2-year period. The intervention consisted of a clinical pharmacist-led strategy intervening on all albumin orders not in accordance with institutional guidelines. The primary end point was to compare inappropriate albumin utilization before and after implementation. Secondary end points compared the rates of inappropriate albumin use adjusted for hospital admission and patient-days as well as associated costs by appropriateness between study periods. RESULTS: A total of 4420 patients were screened, with 1971 (44.6%) patients meeting inclusion criteria. The clinical pharmacist strategy significantly reduced inappropriate albumin (grams) utilization by 86.0% (P < 0.001). A 7-fold reduction of inappropriate albumin administered adjusted for the number of patient admissions was found from the preimplementation period following clinical pharmacist intervention strategy implementation (415.3 ± 83.2 vs 57.5 ± 34.2 g per 100 general ward hospital admissions, respectively; P < 0.001). Also, the adjusted inappropriate albumin rate was reduced from 62.2 ± 12.3 to 8.6 ± 5.2 g per 100 patient-days in the preimplementation and postimplementation periods, respectively (P < 0.001). Annual cost savings were $421 455 overall, with $341 930 resulting from mitigation of inappropriate use. CONCLUSION AND RELEVANCE: Clinical pharmacist-led interventions significantly reduced inappropriate albumin use and costs in hospitalized patients.

Cost-effectiveness analysis of atezolizumab plus nab-paclitaxel for untreated metastatic triple-negative breast cancer.

Aim: To evaluate the cost-effectiveness of atezolizumab plus nab-paclitaxel (ANP) in the first-line treatment of metastatic triple-negative breast cancer (TNBC). Materials & methods: We developed a Markov model to evaluate the cost and effectiveness of ANP versus nab-paclitaxel in the first-line treatment of metastatic TNBC. Lifetime costs, life-years (LYs) and quality-adjusted LYs (QALYs) were estimated. Results: ANP provided an additional 0.16 QALYs (0.24 LYs) compared with nab-paclitaxel in intention-to-treat population. The corresponding incremental cost-effectiveness ratio was $786,131 per QALY gained. However, the incremental cost-effectiveness ratio decreased to $361,218 per QALY gained in the PD-L1 positive subgroup analysis. Conclusion: From the perspective of a US-payer, ANP is estimated not to be cost-effective in the first-line treatment of metastatic TNBC.

Economic model of albumin infusion in septic shock: The EMAISS study.

BACKGROUND: The cost-effectiveness of albumin-based fluid support in patients with septic shock is currently unknown. METHODS: In a simulation study, we compared standard medical practice and systematic 20% albumin infusion. The study population consisted of patients with septic shock admitted to one of the 28 ICUs belonging to the Cub-Réa regional database between 1 January 2014 and 31 December 2016. Cost estimates were based on French diagnosis-related groups and fixed daily prices. Estimation of mortality reduction relied on ALBIOS trial data documenting a Risk Ratio of 0.87 in a non-preplanned subgroup of patients with septic shock. Life expectancy was estimated with follow up data of 184 patients with septic shock admitted in the year 2000 in the same ICUs. Several sensitivity analyses were performed including a one-way Deterministic Sensitivity Analysis (DSA) and a Probabilistic multivariate Sensitivity Analysis (PSA). RESULTS: About 6406 patients were included. In the base-case scenario, the mean live years gained with albumin was 0.49. The mean extra cost of using albumin was €480 per year. The cost per year gained was €974. Sensitivity analyses confirmed the robustness of the results. The probability of albumin being cost-effective was 95% and 97% for a threshold fixed at €20 000 and €30 000 per life-year saved, respectively. CONCLUSION: Based on the risk reduction observed in the septic shock subgroup analysis of the ALBIOS dataset, the application of the ALBIOS trial results to Cub-Réa data may suggest that albumin infusion is likely cost-effective in septic shock.

Clinical Pharmacist-Led Impact on Inappropriate Albumin Use and Costs in the Critically Ill.

Background:Optimal albumin use in the intensive care unit (ICU) remains challenging with inappropriate use approaching 50%. No published reports have described clinical pharmacist impact aimed at mitigating inappropriate albumin use in the ICU. Objective: To evaluate the clinical and economic impact of a clinical pharmacist-led intervention strategy targeting inappropriate albumin in the ICU. Methods: A retrospective cohort study evaluated all adult (≥18 years) ICU patients administered albumin at an academic medical center over a 2-year period. Institutional guidelines were developed with clinical pharmacists targeting inappropriate albumin use. The primary end point was to compare inappropriate use of albumin administered before and after pharmacist intervention implementation. Secondary analyses compared the overall albumin use between study periods. In-hospital mortality, length of stay, and albumin-related costs between study periods were also compared. Results: A total of 4419 patients were identified, with 2448 (55.4%) critically ill patients included. The pharmacist-led strategy resulted in a 50.9% reduction of inappropriate albumin use (P < 0.001). The rate of inappropriate albumin use was 44.3 ± 10.5 and 5.5 ± 2.9 g per patient-day in the preimplementation and postimplementation periods, respectively (P < 0.001). Costs associated with overall and inappropriate albumin use in the ICU decreased by 34.8% and 87.1%, respectively. Total annual cost-savings was $355 393 in the ICUs. No differences in clinical outcomes were found. Conclusion and Relevance: Clinical pharmacist-led interventions reduced overall and inappropriate albumin use and costs without negatively affecting clinical outcomes.

Albumin Usage in Iran.

BACKGROUND: Human albumin is an expensive therapy with inappropriate use in many clinical conditions. Inappropriate use of albumin imposes a substantial economic burden on the healthcare system and society. Drug use evaluation (DUE) is one method of assessing the appropriateness of drug use which has been powered by increasing concern about the cost-effectiveness of drugs. The objective of this study is to systematically review the appropriateness of albumin utilization in Iranian hospitals. METHODS: We searched the PubMed, MEDLINE, EMBASE, SCOPUS, and Google Scholar for articles in English and SID, Magiran, Medlib, and Irandoc for articles in Persian from 1997 to 2018. Studies on the DUE of albumin in Iranian hospitals were included in this study. Articles conducted outside Iran, editorials, letters and review articles were excluded. RESULTS: In total, eight studies were selected for the final review. The majority of the papers were conducted in Tehran. In most studies, the highest albumin consumption was related to the intensive care unit. The most frequent reasons for prescribing albumin were edema, hypoalbuminemia, volume expansion after heart surgery, ascites, cardiac surgery and cirrhosis. Of the studies included, five studies evaluated the costs of drug use. CONCLUSION: Our findings show that inappropriate use of albumin imposes a relatively high additional cost on the society. The included studies show that the percentage of inappropriate use of albumin is relatively high in Iran and this abuse is an essential problem in Iranian hospitals. Prescription based on standard guidelines could improve rational use of albumin and lead to savings in treatment costs.

A Cost-effectiveness Analysis of Albumin in Septic Shock: A Patient-level Data Analysis.

PURPOSE: Albumin-based fluid therapy in septic shock is a matter of debate and criticism. The aim of this study was to assess the cost-effectiveness of albumin therapy in patients with septic shock. METHODS: A retrospective cohort study was conducted in Imam Khomeini, Sina, and Shariati hospitals on patients with septic shock admitted to intensive care units from March 31, 2016 to September 22, 2017. Data sources were the health information system database and patient medical records. The patients with potential septic shock were identified based on norepinephrine use. Septic shock was confirmed after medical record review based on systemic inflammatory response syndrome criteria, antibiotic use, and fluid therapy. Patients who received albumin in the fluid therapy were compared with patients treated without albumin. The 28-day mortality, life-year gain, and cost-effectiveness were evaluated. FINDINGS: The addition of albumin had no significant increase in life-year gain (mean difference = 0.67; 95% CI, -2.25 to 3.58). However, the addition of albumin increased the total cost of treatment by US $3846.07 (95% CI, US $2093.46-US $5598.98). The incremental cost-effectiveness ratio calculated based on the mean life-years gained was US$5740.40 per a life-year gained. The net monetary benefit was negative (-355.4; 95% CI, -15,387.61 to 14,676.81), and the probability that the addition of albumin will be cost-effective at a gross domestic product per capita was 40.0%. IMPLICATIONS: Albumin-based fluid therapy does not improve the 28-day mortality of patients with septic shock. The addition of albumin in the fluid therapy of patients with septic shock was not cost-effective. Both the observational and retrospective nature of the study was expected to introduce bias. We recommend a cost-effectiveness analysis combined with clinical trials to settle the debate once and for all.

Updates in Management and Timing of Dialysis in Acute Kidney Injury.

Acute kidney injury (AKI) is a common complication in hospitalized patients and is associated with mortality, prolonged hospital length of stay, and increased healthcare costs. This paper reviews several areas of controversy in the identification and management of AKI. Serum creatinine and urine output are used to identify and stage AKI by severity. Although standardized definitions of AKI are used in research settings, these definitions do not account for individual patient factors or clinical context which are necessary components in the assessment of AKI. After treatment of reversible causes of AKI, patients with AKI should receive adequate volume resuscitation with crystalloid solutions. Balanced crystalloid solutions generally prevent severe hyperchloremia and could potentially reduce the risk of AKI, but additional studies are needed to demonstrate a clinical benefit. Intravenous albumin may be beneficial in patients with chronic liver disease either to prevent or attenuate the severity of AKI; otherwise, the use of albumin or other colloids (eg, hydroxyethyl starch) is not recommended. Diuretics should be used to treat volume overload, but they do not facilitate AKI recovery or reduce mortality. Nutrition consultation may be helpful to ensure that patients receive adequate, but not excessive, dietary protein intake, as the latter can lead to azotemia and electrolyte disturbances disproportionate to the patient's kidney failure. The optimal timing of dialysis initiation in AKI remains controversial, with conflicting results from two randomized controlled trials.

Is Albumin-based Resuscitation in Severe Sepsis and Septic Shock Justifiable? An Evidence from a Cost-effectiveness Evaluation.

BACKGROUND: Fluid and antimicrobial therapy are the essential parts of sepsis management. The type of fluid to resuscitate with is an unsettled issue in the treatment of severe sepsis and septic shock. The objective of this study was to evaluate the cost-effectiveness of albumin-based resuscitation over crystalloids. METHODS: A cost-effectiveness analysis was conducted by extracting data from a database of Sina Hospital, Islamic Republic of Iran. A decision tree was constructed by using Tree Age Pro 2011. The patients were grouped based on the types of fluids used for resuscitation into crystalloid alone or crystalloid + albumin groups at the initial decision node. The patients were followed from the onset of severe sepsis and septic shock upto 28 days. The healthcare payers' perspective was considered in constructing the model. The cost was measured in US dollars and the effectiveness was measured by life years gained. RESULTS: The addition of albumin during resuscitation of patients with severe sepsis and septic shock has an effectiveness gain of 0.09 life years and cost increment of 495.00 USD. The estimated ICER for this analysis was 5500.00 USD per life year gained. The probability that albumin is cost-effective at one GDP per capita is 49.5%. CONCLUSION: Albumin-based resuscitation is not cost-effective in Iran when a GDP per capita was considered for a life year gain. The cost-effectiveness was insensitive to the cost of standard care. We recomend the caustious use albumin as per the Surviving Sepsis Campaign guideline.

Epidemiology, Pathophysiology, and Management of Hepatorenal Syndrome.

Acute kidney injury (AKI) is a common presentation in patients with advanced cirrhosis hospitalized with acute decompensation. A new revised classification now divides AKI in cirrhotic patients into two broad subgroups: hepatorenal syndrome AKI (HRS AKI) and non-hepatorenal syndrome AKI (non-HRS AKI). HRS AKI represents the end-stage complication of decompensated cirrhosis with severe portal hypertension and is characterized by worsening of renal function in the absence of prerenal azotemia, nephrotoxicity, and intrinsic renal disease. Non-HRS AKI may be caused by prerenal hypoperfusion, bile acid nephropathy, nephrotoxicity, or acute parenchymal insult. There have been several mechanisms proposed to explain the pathophysiology of HRS AKI and non-HRS AKI, and a number of biomarkers have been suggested to aid in differentiation between these types of AKI and to act as prognostic indicators. The standard of care clinical management for patients with HRS AKI is to exclude other etiologies of AKI, followed by volume expansion with human albumin solution and then the introduction of vasopressors. However, some 40% of patients treated for HRS AKI fail to respond. In this review, we discuss the current and recent data about classification, pathophysiology, and management of AKI in general, with specific insight about the treatment of HRS AKI.