Development and Evaluation of an Integrated Outpatient Infusion Care Model for the Treatment of Pediatric Headache.

BACKGROUND: Care for pediatric patients with headache often occurs in high-cost settings such as emergency departments (EDs) and inpatient settings. Outpatient infusion centers have the potential to reduce care costs for pediatric headache management. METHODS: In this quality improvement study, we describe our experience in creating the capacity to support an integrated outpatient pediatric headache infusion care model through an infusion center. We compare costs of receiving headache treatment in this model with those in the emergency and inpatient settings. Because dihydroergotamine (DHE) is a costly infusion, encounters at which DHE was administered were analyzed separately. We track the number of ED visits and inpatient admissions for headache using run charts. As a balancing measure, we compare treatment efficacy between the infusion care model and the inpatient setting. RESULTS: The mean percentage increase in cost of receiving headache treatment in the inpatient setting with DHE was 61% (confidence interval [CI]: 30-99%), and that without DHE was 582% (CI: 299-1068%) compared with receiving equivalent treatments in the infusion center. The mean percentage increase in cost of receiving headache treatment in the ED was 30% (CI: -15 to 100%) compared with equivalent treatment in the infusion center. After the intervention, ED visits and inpatient admissions for headache decreased. The mean change in head pain was similar across care settings. CONCLUSIONS: Our findings demonstrate that developing an integrated ambulatory care model with infusion capacity for refractory pediatric headache is feasible, and our early outcomes suggest this may have a favorable impact on the overall value of care for this population.

Angiotensin II for the treatment of distributive shock in the intensive care unit: A US cost-effectiveness analysis.

BACKGROUND: Patients with distributive shock who are unresponsive to traditional vasopressors are commonly considered to have severe distributive shock and are at high mortality risk. Here, we assess the cost-effectiveness of adding angiotensin II to the standard of care (SOC) for severe distributive shock in the US critical care setting from a US payer perspective. METHODS: Short-term mortality outcomes were based on 28-day survival rates from the ATHOS-3 study. Long-term outcomes were extrapolated to lifetime survival using individually estimated life expectancies for survivors. Resource use and adverse event costs were drawn from the published literature. Health outcomes evaluated were lives saved, life-years gained, and quality-adjusted life-years (QALYs) gained using utility estimates for the US adult population weighted for sepsis mortality. Deterministic and probabilistic sensitivity analyses assessed uncertainty around results. We analyzed patients with severe distributive shock from the ATHOS-3 clinical trial. RESULTS: The addition of angiotensin II to the SOC saved .08 lives at Day 28 compared to SOC alone. The cost per life saved was estimated to be $108,884. The addition of angiotensin II to the SOC was projected to result in a gain of .96 life-years and .66 QALYs. This resulted in an incremental cost-effectiveness ratio of $12,843 per QALY. The probability of angiotensin II being cost-effective at a threshold of $50,000 per QALY was 86 percent. CONCLUSIONS: For treatment of severe distributive shock, angiotensin II is cost-effective at acceptable thresholds.

The Headache Pipeline: Excitement and Uncertainty.

There are many new treatment options available for migraine and more are coming. Three calcitonin gene-related peptide (CGRP) antagonist monoclonal antibodies have been approved and a 4th is due in early 2020. Small molecule CGRP receptor-blocking oral compounds, both for acute care and prevention, are also coming. Four neurostimulators are available, with others on the way. New acute treatments coming soon include the 5HT1F agonist lasmiditan, a zolmitriptan intradermal micro-needle patch, and a nasal mist sumatriptan with a permeability enhancer. Farther out, three novel dihydroergotamine delivery systems, and a liquid-filled capsule of celecoxib show early promise. A new, safer form of methysergide is in the works, as is a longer-duration onabotulinumtoxinA. As always with new products, questions regarding safety, tolerability, cost, and insurance coverage will need to be addressed. Despite these concerns and uncertainties, a robust headache treatment pipeline is good for patients who are not satisfied with the results of their treatment and/or cannot tolerate existing treatments.

Delayed vasopressor initiation is associated with increased mortality in patients with septic shock.

PURPOSE: Mortality rate for septic shock, despite advancements in knowledge and treatment, remains high. Treatment includes administration of broad-spectrum antibiotics and stabilization of the mean arterial pressure (MAP) with intravenous fluid resuscitation. Fluid-refractory shock warrants vasopressor initiation. There is a paucity of evidence regarding the timing of vasopressor initiation and its effect on patient outcomes. MATERIALS AND METHODS: This retrospective, single-centered, cohort study included patients with septic shock from January 2017 to July 2017. Time from initial hypotension to vasopressor initiation was measured for each patient. The primary outcome was 30-day mortality. RESULTS: Of 530 patients screened,119 patients were included. There were no differences in baseline patient characteristics. Thirty-day mortality was higher in patients who received vasopressors after 6 h (51.1% vs 25%, p < .01). Patients who received vasopressors within the first 6 h had more vasopressor-free hours at 72 h (34.5 h vs 13.1, p = .03) and shorter time to MAP of 65 mmHg (1.5 h vs 3.0, p < .01). CONCLUSION: Vasopressor initiation after 6 h from shock recognition is associated with a significant increase in 30-day mortality. Vasopressor administration within 6 h was associated with shorter time to achievement of MAP goals and higher vasopressor-free hours within the first 72 h.

Cost-effectiveness of second-line vasopressors for the treatment of septic shock.

PURPOSE: To determine the cost-effectiveness of escalating doses of norepinephrine or norepinephrine plus the adjunctive use of vasopressin or angiotensin II as a second-line vasopressor for septic shock. MATERIALS AND METHODS: Decision tree analysis was performed to compare costs and outcomes associated with norepinephrine monotherapy or the two adjunctive second-line vasopressors. Short- and long-term outcomes modeled included ICU survival and lifetime quality-adjusted-life-years (QALY) gained. Costs were modeled from a payer's perspective, with a willingness-to-pay threshold set at $100,000/unit gained. One-way (tornado diagrams) and probabilistic sensitivity analyses were performed. RESULTS: Adjunctive vasopressin was the most cost-effective therapy, and dominated both norepinephrine monotherapy and adjunctive angiotensin II by producing higher ICU survival at less cost. For the lifetime horizon, while norepinephrine monotherapy was least expensive, adjunctive vasopressin was the most cost-effective with an incremental cost-effectiveness ratio of $19,762 / QALY gained. Although adjunctive angiotensin II produced more QALYs compared to norepinephrine monotherapy, it was dominated in the long-term evaluation by second-line vasopressin. Sensitivity analyses demonstrated model robustness and medication costs were not significant drivers of model results. CONCLUSIONS: Vasopressin is the most cost-effective second-line vasopressor in both the short- and long-term evaluations. Vasopressor price is a minor contributor to overall cost.

Charge Reductions Associated With Shorter Time to Recovery in Septic Shock.

BACKGROUND: Septic shock therapies that shorten the time to physiologic and clinical recovery may result in financial savings. However, the financial implications of improving these nonmortal outcomes are not well characterized. Therefore, we quantified hospital charges associated with four outcomes: ICU length of stay, duration of invasive mechanical ventilation, duration of vasopressor use, and new renal replacement therapy. METHODS: This was an observational study using administrative data from a large academic hospital in the United States. The analysis included adults treated with vasopressors for septic shock in a medical ICU. Linear regression modeling with ordinary least square was used to estimate the incremental hospital charges associated with 1 day of ICU length of stay, 1 day of mechanical ventilation, 1 day of vasopressor use, and new renal replacement therapy. RESULTS: The study population included 587 adults with septic shock, including 180 (30.7%) who died in the hospital. The median charge for a septic shock hospitalization was $98,583 (interquartile range [IQR], $61,177-$136,672). Decreases in ICU length of stay, mechanical ventilation duration, and vasopressor duration of 1 day were associated with charge reductions of $15,670 (IQR, $15,023-$16,317), $15,284 (IQR, $13,566-$17,002), and $17,947 (IQR, $16,344-$19,549), respectively. Avoidance of new renal replacement therapy was associated with a charge reduction of $36,051 (IQR, $22,353-$49,750). CONCLUSIONS: Septic shock therapies that reduce the duration of organ support and ICU care have the potential to lead to substantial financial savings.

Allergy and Asthma: Anaphylaxis.

Anaphylaxis is an allergic reaction that occurs rapidly after exposure and is life-threatening. After symptoms of anaphylaxis occur, there is no way to reliably predict whether the patient's condition could progress quickly and become life-threatening. Immediate injection of intramuscular epinephrine is the first-line emergency treatment for anaphylaxis. Other drugs such as corticosteroids or antihistamines are secondary options and should not delay epinephrine administration. The most commonly prescribed form of epinephrine is the costly brand name autoinjector, but less expensive alternatives exist, including generic autoinjectors and prefilled epinephrine syringes. Epinephrine prescriptions should be combined with action plans that guide parents and caregivers on appropriate use. Access to epinephrine at schools, even for students who do not have a prescription, is an important component of preparedness for anaphylaxis.

Hyperinflation of Vasopressors (Vasopressin, Norepinephrine, Ephedrine, etc).

PURPOSE: Hyperinflation refers to the increasing cost of drugs which occurs due to continued drug shortages and rebranding. Hyperinflation has significant implications in increasing overall healthcare costs with reduced reimbursement, increased patient acuity, and an aging population, but published strategies to reduce costs and minimize waste are limited. OBJECTIVE: To describe the hyperinflation and cost mitigation strategies of three vasopressor medications, vasopressin, epinephrine, and ephedrine. CONCLUSION: The steep increase in medications is expected to continue, and mitigation strategies to reduce waste and select the most cost effective therapy to offset the price increase is crucial for healthcare systems.

Mortality, intensive care treatment, and cost evaluation: Role of a polymerase chain reaction assay in patients with sepsis.

Objective We examined whether patients with a positive SeptiFast (SF) assay (LightCycler SeptiFast; Roche Diagnostics, Basel, Switzerland) developed higher long-term mortality, a more difficult course of treatment, and a higher antimicrobial treatment cost than patients with a negative SF assay. Methods We performed a post-hoc analysis of data collected in a 1-year prospective interventional study of adults with severe sepsis and septic shock. In addition to the standard treatment, an additional 5 ml of blood was obtained for an SF assay, and the antimicrobial treatment was changed according to the SF results. Results We included 57 patients, and the SF assay was positive (SF+) in 10 (17.5%) and negative (SF-) in 47 (82.5%) patients. A trend toward a higher 6-month, 1-year, and 2-year mortality rate was observed in the SF+ group. In the SF+ group, we observed a significantly greater need for second-line vasopressor therapy, a higher initial procalcitonin concentration, and higher maximum C-reactive protein and lactate concentrations. We found no significant differences in cost of antimicrobial treatment between the SF+ and SF- groups. Conclusions We observed a trend toward higher long-term mortality and a more difficult course of treatment but no difference in the cost of antimicrobial treatment.

Wide Awake Hand Surgery.

Wide awake hand surgery employs local-only anesthesia with low-dose epinephrine to create a bloodless field without the use of an arm tourniquet. Despite traditional teaching, evidence-based medicine suggests epinephrine is safe for use in hand and digital anesthesia. Eliminating an arm tourniquet reduces the requirement for sedation and general anesthetic. This confers particular advantage in surgeries such as tendon repairs, tendon transfers, and soft tissue releases in which intraoperative active motion can used to optimize outcomes. The wide awake approach also confers significant benefit to patients, providers, and health care systems alike due to efficiencies and cost savings.

Relative costs of anesthesiologist prepared, hospital pharmacy prepared and outsourced anesthesia drugs.

BACKGROUND: Anesthesia drugs can be prepared by anesthesia providers, hospital pharmacies or outsourcing facilities. The decision whether to outsource all or some anesthesia drugs is challenging since the costs associated with different anesthesia drug preparation methods remain poorly described. METHODS: The costs associated with preparation of 8 commonly used anesthesia drugs were analyzed using a budget impact analysis for 4 different syringe preparation strategies: (1) all drugs prepared by anesthesiologist, (2) drugs prepared by anesthesiologist and hospital pharmacy, (3) drugs prepared by anesthesiologist and outsourcing facility, and (4) all drugs prepared by outsourcing facility. MAIN RESULTS: A strategy combining anesthesiologist and hospital pharmacy prepared drugs was associated with the lowest estimated annual cost in the base-case budget impact analysis with an annual cost of $225 592, which was lower than other strategies by a margin of greater than $86 000. CONCLUSION: A combination of anesthesiologist and hospital pharmacy prepared drugs resulted in the lowest annual cost in the budget impact analysis. However, the cost of drugs prepared by an outsourcing facility maybe lower if the capital investment needed for the establishment and maintenance of the US Pharmacopeial Convention Chapter <797> compliant facility is included in the budget impact analysis.

Noradrenaline is as Effective as Terlipressin in Hepatorenal Syndrome Type 1: A Prospective, Randomized Trial.

OBJECTIVES: Hepatorenal syndrome (HRS) is a functional renal failure occurring in end stage liver disease, which is associated with poor prognosis. Terlipressin has been shown to be effective in treatment of HRS. More recently, it was suggested that noradrenaline, an alpha-adrenergic drug may be also effective in HRS. We aimed to compare the efficacy of noradrenaline versus terlipressin in treatment of HRS type 1. METHODS: Consecutive patients with cirrhosis and HRS type 1 were enrolled and randomised into 2 groups- Group A received intravenous noradrenaline infusion (0.5-3 mg/h) and group B received intravenous terlipressin (0.5-2 mg/6h) for 2 weeks. Intravenous albumin (20 g/day) was given to both groups. RESULTS: Out of 55 cirrhotics screened, 41 were randomised into group A (n=21) or group B (n=20). Baseline characteristics of the two groups were similar. HRS reversal was seen in 47.6%(10/21) patients in group A, and 45% (9/20) patients in group B (p=1.00). In both groups, there was a significant decrease in serum creatinine from baseline (group A- 3.1±1.4 mg/dl to 2.2±1.3 mg/dl, p=0.028; group B- 3.4±1.6 mg/dl to 2.3±1.3 mg/dl, p=0.035). Both the groups showed a significant increase in mean arterial pressure (group A- 77.3±8.6 mmHg to 103.4±8.3 mmHg, p=0.0001; group B- 76.8±11.6 mmHg to 100±9.4 mmHg, p=0.0001). Noradrenaline was associated with fewer adverse events and was significantly cheaper than terlipressin. Lower baseline MELD score was an independent predictor of response to treatment. CONCLUSIONS: Noradrenaline is as effective and safe as terlipressin in the treatment of HRS type 1.

TERLIPRESSIN VERSUS NORADRENALINE FOR HEPATORENAL SYNDROME. Economic evaluation under the perspective of the Brazilian Public Health System.

BACKGROUND: - Terlipressin and noradrenaline are the best studied treatments for hepatorenal syndrome, and there is no evidence of superiority of one over the other regarding to efficacy. While the former drug is more costly, the latter requires admission into an intensive care unit. OBJECTIVE: - The aim of this study was to perform an economic evaluation, comparing treatments for hepatorenal syndrome with terlipressin and noradrenaline. METHODS: - For the economic evaluation, a cost-minimization analysis was performed. Direct medical costs of the two treatment strategies were compared under the perspective of the Brazilian Public Health System as the third-party payer. A probabilistic sensitivity analysis was performed. RESULTS: - The costs of treatments with terlipressin or noradrenaline were 287.77 and 2,960.45 International Dollars (Int$) respectively. Treatment using terlipressin would save Int$2,672.68 for the Public Health System for each hospital admission related to hepatorenal syndrome. In the probabilistic sensitivity analysis, it was verified that the cost of the treatment with noradrenaline could vary between Int$2,326.53 and Int$3,644.16, while costs related to the treatment using terlipressin are not variable. CONCLUSION: - The treatment strategy using terlipressin was more economical than that using noradrenaline under the perspective of the Brazilian Public Health System as the third-party payer.

Terlipressin versus noradrenaline in the treatment of hepatorenal syndrome: systematic review with meta-analysis and full economic evaluation.

OBJECTIVE: The aim of this study was to compare the efficacy and costs of terlipressin and noradrenaline for the treatment of hepatorenal syndrome from the perspective of the Brazilian public health system and that of a major private health insurance. METHODS: Comparison of efficacy was performed through a systematic review with a meta-analysis of randomized-controlled trials using a random-effects model. Economic evaluation was carried out through cost minimization. RESULTS: Four studies (154 patients) were included in the meta-analysis. There was no evidence of a difference between treatments with terlipressin or noradrenaline in terms of 30-day survival (risk ratio=1.04, 95% confidence interval=0.84-1.30, P=0.70). From the perspective of the public health system, costs of the treatments with terlipressin or noradrenaline were Int$7437.04 and Int$8406.41, respectively. From the perspective of the private health insurance, costs of treatments with terlipressin and noradrenaline were Int$13,484.57 and Int$15,061.01, respectively. CONCLUSION: There was no evidence of superiority between treatment strategies using terlipressin or noradrenaline in terms of the survival of patients with hepatorenal syndrome, but the strategy using terlipressin was more economical under two different perspectives.

Noradrenaline or terlipressin for hepatorenal syndrome?

Hepatorenal syndrome is a condition associated with very high mortality that may be reverted in some cases with vasoconstrictors. Terlipressin has generally been considered standard treatment, but noradrenaline has been postulated as alternative. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified six systematic reviews including four pertinent randomized controlled trials. We combined the evidence using meta-analysis and generated a summary of findings following the GRADE approach. We concluded noradrenaline and terlipressin probably have similar effects on reverting hepatorrenal syndrome and decreasing mortality, but noradrenaline is associated with less adverse effects, and has lower costs.

El síndrome hepatorrenal es una condición asociada a altísima mortalidad, que puede ser recuperada en ciertos casos con el uso de vasoconstrictores. Generalmente se considera que terlipresina es el tratamiento estándar, pero noradrenalina se ha planteado como una alternativa. Utilizando la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en 30 bases de datos, identificamos seis revisiones sistemáticas que en conjunto incluyen cuatro estudios aleatorizados. Realizamos un metanálisis y tablas de resumen de los resultados utilizando el método GRADE. Concluimos que noradrenalina y terlipresina son probablemente igual de efectivas en lograr mejoría del síndrome hepatorrenal y disminuir la mortalidad, pero que noradrenalina se asocia a menos efectos adversos, y tiene un menor costo.

An official American Thoracic Society/American College of Chest Physicians policy statement: the Choosing Wisely top five list in adult pulmonary medicine.

The American Board of Internal Medicine Foundation's Choosing Wisely campaign aims to curb health-care costs and improve patient care by soliciting lists from medical societies of the top five tests or treatments in their specialty that are used too frequently and inappropriately. The American Thoracic Society (ATS) and American College of Chest Physicians created a joint task force, which produced a top five list for adult pulmonary medicine. Our top five recommendations, which were approved by the executive committees of the ATS and American College of Chest Physicians and published by Choosing Wisely in October 2013, are as follows: (1) Do not perform CT scan surveillance for evaluation of indeterminate pulmonary nodules at more frequent intervals or for a longer period of time than recommended by established guidelines; (2) do not routinely offer pharmacologic treatment with advanced vasoactive agents approved only for the management of pulmonary arterial hypertension to patients with pulmonary hypertension resulting from left heart disease or hypoxemic lung diseases (groups II or III pulmonary hypertension); (3) for patients recently discharged on supplemental home oxygen following hospitalization for an acute illness, do not renew the prescription without assessing the patient for ongoing hypoxemia; (4) do not perform chest CT angiography to evaluate for possible pulmonary embolism in patients with a low clinical probability and negative results of a highly sensitive D-dimer assay; (5) do not perform CT scan screening for lung cancer among patients at low risk for lung cancer. We hope pulmonologists will use these recommendations to stimulate frank discussions with patients about when these tests and treatments are indicated--and when they are not.

[Economic impact of strategies using ephedrine prefilled syringes]. / Impact économique des stratégies de recours à l'éphédrine en seringues préremplies.

OBJECTIVES: Ephedrine is an emergency drug available in ampules and syringes need to be prepared in advance according to one of two strategies in our establishment: strategy 1 (S1: 1 ampule per patient) and strategy 2 (S2: 1 ampule per operating room). There are also prefilled syringes. Because of their high cost and conflicting results in the literature, we assessed the economic interest of using prefilled syringes compared with strategies S1 and S2. TYPE OF STUDY: This was a prospective observational study. PATIENTS AND METHODS: The consumption of ephedrine was recorded over two periods of 14 days: P1 with syringes prepared in advance according to S1 or S2 and P2 with the on-demand use of prefilled syringes. RESULTS: The cost of a syringe of ephedrine prepared in advance (nurse time preparation included) was evaluated at €1.65 vs. €3.57 for a prefilled syringe. In operating rooms using S1, the use of prefilled syringes reduced overall the cost per patient about €1.22 and global annual costs by 72% (€2830), while the decrease was about €0.32 for the cost per patient and about 47% (€2760) for global annual costs for operating rooms using S2. CONCLUSION: The interest of our study is that we investigated different supply strategies for ephedrine within a large number of operating rooms. In our establishment, it was decided to use prefilled syringes in operating rooms that used S1. As well as the economic interest, prefilled syringes contributed to improved safety and saved nursing time.