Pulmonary hypertension in infants with bronchopulmonary dysplasia: risk factors, mortality and duration of hospitalisation.

OBJECTIVES: Pulmonary hypertension (PH) is a complication of bronchopulmonary dysplasia (BPD) and associated with increased mortality and morbidity. Our aim was to identify, in infants with BPD, the effect of PH on health-care utilisation and health related cost of care. METHODS: An electronic data recording system was used to identify infants ≤32 weeks of gestation who developed BPD. PH was classified as early (≤28 days after birth) or late (>28 days after birth). RESULTS: In the study period, 182 infants developed BPD; 22 (12.1%) developed late PH. Development of late PH was associated with a lower gestational age [24.6 (23.9-26.9) weeks, p=0.001] and a greater need for positive pressure ventilation on day 28 after birth (100%) compared to infants without late PH (51.9%) (odds ratio (OR) 19.5, 95% CI: 2.6-148), p<0.001. Late PH was associated with increased mortality (36.4%) compared those who did not develop late PH (1.9%) after adjusting for gestational age and ventilation duration (OR: 26.9, 95% CI: 3.8-189.4), p<0.001. In infants who survived to discharge, late PH development was associated with a prolonged duration of stay [147 (118-189) days] compared to the infants that did not develop late PH [109 (85-149) days] (p=0.03 after adjusting for gestational age). Infants who had late PH had a higher cost of stay compared to infants with BPD who did not develop late PH (median £113,494 vs. £78,677, p=0.016 after adjusting for gestational age). CONCLUSIONS: Development of late PH was associated with increased mortality, a prolonged duration of stay and higher healthcare cost.

Utility of Endoscopy in Hospitalized Patients with Gastrointestinal Hemorrhage and Pulmonary Hypertension.

BACKGROUND: Gastrointestinal hemorrhage (GIH) has been reported as one of the most common GI complications in patients with pulmonary hypertension (PH). There is paucity of data on the national burden of GIH in patients with PH. We aimed to assess the prevalence, trends and outcomes of endoscopic interventions in patients with PH who were admitted with GIH. METHOD: We queried National Inpatient Sample (NIS) database from 2005 to 2014 and identified the patients hospitalized with primary or secondary discharge diagnosis of PH (ICD 9 CM Code: 416.0, 416.8, and 416.9). Using Clinical Classification Software Coding system (153) patients with concurrent diagnosis of GIH were then identified. We studied the prevalence and trends of GIH in PH, factors associated with GIH, use of endoscopy, factors associated with utilization of endoscopic interventions, endoscopy outcomes including mortality, and overall healthcare burden. RESULTS: Out of 7,586,973 PH hospitalizations 3.2% (N = 246,358) had concurrent GIH, with a rising prevalence of GIH in PH patients during the last decade. Clinical predictors for GIH in PH included older age, congestive heart failure, anticoagulation therapy and concurrent alcohol abuse. Mean length of stay (LOS) in PH patients hospitalized with GIH was significantly higher than without GIH (8.6 vs. 6.4 days, p < 0.01) along with a significant increase in hospitalization cost ($20,189 vs. $14,807, p < 0.01). Similarly, odds of in-hospital mortality increase by ~ 1.5 times in PH patients with GIH than those without it (adjusted odds ratio [aOR: 1.45, 95%CI: 1.43-1.47]). Endoscopic interventions were performed in 48.6% of patients with PH and GIH during their hospitalization. Older patients were more likely to undergo endoscopy, as well as the patients who received blood transfusion, and those with hypovolemic shock. Patients with acute respiratory failure and acute renal failure were less likely to get endoscopy. Mean LOS in patients undergoing endoscopic intervention was significantly higher than those who did not receive any intervention (8.7 vs. 8.4 days, p < 0.01), without a substantial increase in hospitalization cost ($20,344 vs. $20,041, p < 0.01). Also, there was a significant decrease in in-hospital mortality in patients undergoing endoscopic interventions. CONCLUSION: Concurrent GIH in patients with PH increases length of stay; healthcare costs and increases in-hospital mortality. Use of endoscopic interventions in these patients is associated with reduced length of stay, in-hospital mortality without significantly increasing the overall health care burden and should be considered in hospitalized patients with PH who are admitted with GIH. Future studies comparing GIH patients with and without PH should be done to assess if PH is a risk factor for worse outcomes. CLINICAL TRIAL REGISTRATION NUMBER: No IRB required due to use of national de-identified data.

Economic burden of incident interstitial lung disease (ILD) and the impact of comorbidity on costs of care.

INTRODUCTION: Evidence about the economic burden related to interstitial lung diseases (ILDs) and the cost-driving factors is sparse. In the knowledge that distinct comorbidities affect the clinical course of ILDs, our study investigates their impact on costs of care within first year after diagnosis. METHODS: Using claims data of individuals diagnosed with Idiopathic Interstitial Pneumonia (IIP) (n = 14 453) or sarcoidosis (n = 9106) between 2010 and 2013, we calculated total and ILD-associated mean annual per capita costs adjusted by age, sex and comorbidity burden via Generalized Linear Gamma models. Then, we assessed the cost impact of chronic obstructive pulmonary disease (COPD), diabetes, coronary artery disease, depression, gastro-esophageal reflux disease, pulmonary hypertension (PH), obstructive sleep apnoea syndrome (OSAS) and lung cancer using the model-based parameter estimates. RESULTS: Total mean annual per capita costs were €11 131 in the pooled cohort, €12 111 in IIP and €8793 in sarcoidosis, each with a 1/3 share of ILD-associated cost. Most comorbidities had a significant cost-driving effect, which was most pronounced for lung cancer in total (1.989 pooled, 2.491 sarcoidosis, 1.696 IIP) and for PH in ILD-associated costs (2.606 pooled, 2.347 IIP, 3.648 sarcoidosis). The lung-associated comorbidities COPD, PH, OSAS more strongly affected ILD-associated than total costs. CONCLUSION: Comorbidities increase the already substantial costs of care in ILDs. To support patient-centred ILD care, not only highly cost-driving conditions that are inherent with high mortality themselves require systematic management. Moreover, conditions that are more rather restricting the patient's activities of daily living should be addressed - despite a low-cost impact.

A Comparison of Inhaled Nitric Oxide Versus Inhaled Epoprostenol for Acute Pulmonary Hypertension Following Cardiac Surgery.

BACKGROUND: Direct comparisons of inhaled nitric oxide (iNO) to inhaled epoprostenol (iEPO) in patients with acute pulmonary hypertension (PHT) following cardiac surgery are lacking. OBJECTIVE: To compare the relative efficacy, safety, and cost of iNO versus iEPO in patients with acute PHT following cardiac surgery. METHODS: This is a single-center, retrospective, observational, cohort study comparing iNO to iEPO for acute postoperative PHT following cardiac surgery. The primary outcome was reduction of mean pulmonary artery pressure (mPAP) to < 30 mm Hg, 6 hours after ICU admission from the operating room. Secondary outcomes, included ICU and hospital length of stay, duration of mechanical ventilation, bleeding complications, hypotension, in-hospital mortality, and cost. RESULTS: A total of 98 patients met inclusion criteria (iNO, n = 49; iEPO, n = 49). There was no difference in the primary outcome of reduction of mPAP to < 30 mm Hg 6 hours after ICU admission (iNO, 33 [67%] vs iEPO, 35 [71%]; P = 0.83) or in the incidence of adverse events collected (iNO, 10 [20%] vs iEPO, 11 [22%]; P = 1.00). Based on cost estimates, the median cost of iEPO per patient was $363.53 ($226-$864.60) versus $2562.50 ($1875-$8625) for iNO (P < 0.01). CONCLUSIONS: The relative efficacy of iEPO appeared to be similar to that of iNO in reducing mPAP following cardiac surgery, in this retrospective review. Significant cost savings were associated with the use of iEPO.

Cost savings with a new screening algorithm for pulmonary arterial hypertension in systemic sclerosis.

BACKGROUND: Screening for pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc) is now standard care in this disease. The existing Australian Scleroderma Interest Group algorithm (ASIGSTANDARD ) is based on transthoracic echocardiography (TTE) and pulmonary function tests (PFT). Recently, ASIG has derived and validated a new screening algorithm (ASIGPROPOSED ) that incorporates N-terminal pro-B-type natriuretic peptide level together with PFT in order to decrease reliance on TTE, which has some limitations. Right heart catheterisation (RHC) remains the gold standard for the diagnosis of PAH in patients who screen 'positive'. AIM: To compare the cost of PAH screening in SSc with ASIGSTANDARD and ASIGPROPOSED algorithms. METHODS: We applied both ASIGSTANDARD and ASIGPROPOSED algorithms to 643 screen-naïve SSc patients from the Australian Scleroderma Cohort Study (ASCS), assuming a PAH prevalence of 10%. We compared the costs of screening, the number of TTE required and both the total number of RHC required and the number of RHC needed to diagnose one case of PAH, and costs, according to each algorithm. We then extrapolated the costs to the estimated total Australian SSc population. RESULTS: In screen-naïve patients from the ASCS, ASIGPROPOSED resulted in 64% fewer TTE and 10% fewer RHC compared with ASIGSTANDARD , with $1936 (15%) saved for each case of PAH diagnosed. When the costs were extrapolated to the entire Australian SSc population, there was an estimated screening cost saving of $946 000 per annum with ASIGPROPOSED , with a cost saving of $851 400 in each subsequent year of screening. CONCLUSIONS: ASIGPROPOSED substantially reduces the number of TTE and RHC required and results in substantial cost savings in SSc-PAH screening compared with ASIGSTANDARD .

Demographics, clinical characteristics, health resource utilization and cost of chronic thromboembolic pulmonary hypertension patients: retrospective results from six European countries.

BACKGROUND: Chronic Thromboembolic Pulmonary Hypertension (CTEPH) results from incomplete resolution of a pulmonary embolus, leading to pulmonary hypertension and progressive right heart failure and death. We aimed to describe the demographics, treatment patterns, health resource utilization and related costs of patients with CTEPH. METHODS: In specialized PH centres across six European countries, medical charts of CTEPH patients on PH medication were retrospectively extracted (chart review between 2006 and 2009). Resource utilization was valued using country-specific unit costs. Descriptive statistical analyses were performed. RESULTS: Twenty-one hospitals documented 119 consecutive CTEPH patients over an average of 25.4 months. Patients were inoperable (83.9%) or persistent after surgery (16.0%) with mean age 67.5 ± 12.3 years, 61% were female. The average 6-minute walking distance was 298 ± 120 meters, and NYHA class II/III/IV was 27/59/14%. At baseline, 59.7% patients received endothelin receptor antagonist, 34.4% phosphodiesterase-5 inhibitors, and 5.8% prostacyclin. Adding a second PH medication was the most common regimen change. CTEPH patients experienced 1.8 ± 2.2 hospitalizations per year accounting for 14.8 ± 26.1 days in hospital. Patients paid on average 2.8 office visits per year to their general practitioner and 1.3 visits to a specialist. Unadjusted annual mortality rate was 6.0%. Annual cost of PH specific medication was the predominant economic factor averaging € 36,768 per year. Costs for hospitalizations (€ 4,496) and concomitant medications (€ 2,510) were substantially lower. Other health care resource items only accounted for marginal additional costs. CONCLUSION: CTEPH patients are characterised by substantial morbidity and mortality. Health care utilisation, predominantly due to off-label use of PH drugs, is significant.

[Efficiency of initiation with ambrisentan versus bosentan in the treatment of pulmonary arterial hypertension]. / Eficiencia del inicio con ambrisentan frente a bosentan en el tratamiento de la hipertensión arterial pulmonar.

OBJECTIVE: To evaluate the efficiency of initiation with endothelin receptor antagonists, ambrisentan or bosentan, followed by sequential combination with phosphodiesterase-5 inhibitors and prostanoids in the treatment of pulmonary arterial hypertension, from the Spanish National Health System perspective. METHODS: A Markov model was developed based on the four New York Heart Association functional classes. A panel of three experts reached a consensus on patient management based on clinical practice. Patients revised their treatment every 12 weeks, based on their health status and previous medication records. Pharmacological treatment costs and costs associated with very frequent adverse events (AE) were considered in a horizon of 60 weeks. Outcomes were measured in qualityadjusted life years (QALY). A probabilistic sensitivity analysis was performed. RESULTS: No clinically relevant differences in QALY per-patient and year were found for initiation with ambrisentan and bosentan: 0.6853 and 0.6902, respectively. Initiation with ambrisentan resulted in lower pharmacological treatment and AE management costs: ?35,550 and ?117 versus ?40,224 and ?171. In the sensitivity analysis, initiation with ambrisentan resulted in a negative significant cost difference: ?-4,982; CI95%[?- 8,014; ?-2,500]; while no significant differences in QALY were found: -0.0044; CI95%[-0.0189; 0.0101]. CONCLUSIONS: Initiation with ambrisentan followed by sequential combination with phosphodiesterase-5 inhibitors and prostanoids yields comparable outcomes at lower costs than initiation with bosentan.

Objetivo: Se pretende evaluar la eficiencia del tratamiento secuencial de combinación de la hipertensión arterial pulmonar iniciado con antagonistas del receptor de la endotelina, ambrisentan o bosentan, seguido de inhibidores de la fosfodiesterasa- 5 y prostanoides, desde la perspectiva del Sistema Nacional de Salud. Métodos: Se desarrolló un modelo de Markov basado en las cuatro clases funcionales de la New York Heart Association. Un panel de tres expertos alcanzó un consenso sobre el manejo del paciente basado en la práctica clínica. Los pacientes revisaron su tratamiento cada 12 semanas, en función de su estado de salud y de la medicación recibida previamente. Se incluyeron costes farmacológicos y costes asociados al manejo de eventos adversos (EA) muy frecuentes, en un horizonte de 60 semanas. Los resultados se expresaron en términos de los años de vida ajustados por calidad (AVAC). Se realizó un análisis de sensibilidad probabilístico. Resultados: No se encontraron diferencias clínicamente relevantes en los AVAC por paciente y año para el inicio con ambrisentan y bosentan: 0,6853 y 0,6902, respectivamente. El inicio con ambrisentan resultó en un coste farmacológico y asociado al manejo de EA menor: 35.550 ??y 117 ??frente a 40.224 ??y 171 ?. En el análisis de sensibilidad, el inicio con ambrisentan presentó una diferencia de costes totales negativa y significativa: -4.982 ?; IC95%[-8.014 ?; -2.500 ?]; mientras que no se detectaron diferencias significativas en los AVAC: -0,0044; IC95%[-0,0189; 0,0101]. Conclusiones: El tratamiento secuencial de combinación de la HAP iniciado con ambrisentan, seguido de inhibidores de la fosfodiesterasa- 5 y prostanoides, proporciona resultados en salud comparables y menores costes que el tratamiento iniciado con bosentan.

Optimizing cost-effectiveness in perioperative care for liver transplantation: a model for low- to medium-income countries.

Although liver transplantation (LT) is a highly effective treatment, it has been considered too costly for publicly funded health systems in many countries with low to medium average incomes. However, with economic growth and improving results, some governments are reconsidering this position. Cost-effectiveness data for LT are limited, especially in perioperative care, and the techniques and costs vary widely between centers without overt differences in outcomes. Anesthesiologists working in new programs find it difficult to determine which modalities are essential, which are needed only in exceptional circumstances, and which may be omitted without effects on outcomes. We investigated key elements of preoperative evaluations, intraoperative management, and early postoperative care that might significantly affect costs in order to develop a best-value approach for new programs in resource-limited health systems. We identified all modalities of care commonly used in anesthesia and perioperative care for adult LT along with their costs. Those considered to be universally accepted as minimum requirements for safe care were excluded from the analysis, and so were those considered to be safe and low-cost, even when evidence of efficacy was lacking. The remaining items were, therefore, those with uncertain or context-restricted value and significant costs. A systematic review of the published evidence, practice surveys, and institutional guidelines was performed, and the evidence was graded and summarized. With respect to costs and benefits, each modality was then cited as strongly recommended, recommended or optional, or no recommendation was made because of insufficient evidence. Sixteen modalities, which included preoperative cardiovascular imaging, venovenous bypass, pulmonary artery catheterization, high-flow fluid warming devices, drug therapies for hemostasis, albumin, cell salvage, anesthetic drugs, personnel (staffing) requirements, and early extubation, were assessed. Only high-flow fluid warming was strongly recommended. The recommended modalities included preoperative echocardiography, cell salvage, tranexamic acid and early extubation. Six others were rated optional, and there was insufficient evidence for 5 modalities. We conclude that some costly techniques and treatments can be omitted without adverse effects on outcomes.

The cost-effectiveness of bosentan in the United Kingdom for patients with pulmonary arterial hypertension of WHO functional class III.

OBJECTIVES: To assess whether bosentan or no active intervention, in addition to palliative care, is the more cost-effective first-line treatment option for patients with idiopathic pulmonary arterial hypertension (iPAH) or PAH associated with connective tissue disease (PAH-CTD) of WHO functional classification (FC) III in the United Kingdom. METHODS: A cost-utility model simulated the treatment of patients with PAH of FC III. Patients remained on the selected intervention until death or clinical deterioration to FC IV, which would trigger initiation of epoprostenol treatment. The initial first-line treatment choice was assumed to not affect survival, but to affect the time until clinical deterioration, with this assumption being relaxed in sensitivity analyses. The distribution of time to clinical deterioration was estimated from long-term clinical trial databases of bosentan and from published literature. Utility associated with FC was taken from published literature. Costs were sourced from published literature and from specialist PAH centers. The time horizon was that of patients' lifetimes, with costs and benefits discounted at 3.5% per annum. RESULTS: In the base case, bosentan dominated no active intervention because of the longer time to clinical deterioration and therefore the reduced time, per patient, spent in FC IV, which was associated with high costs of epoprostenol and reduced utility. In sensitivity analyses, bosentan was estimated to be more cost-effective than no active intervention, provided that any survival benefit was not greater than 2 years for patients with iPAH and 1 year for those with PAH-CTD. CONCLUSIONS: Bosentan is likely to be a more cost-effective first-line therapy for patients with PAH FC III in the UK than no active intervention.

[Treatment for pulmonary arterial hypertension under the new French hospital financing system. Recommendations of the Pulmonary Vascular Diseases Working Group of the French Society of Pulmonary Medicine]. / Les traitements de l'hypertension artérielle pulmonaire à l'heure de la T2A. Recommandations du groupe de travail "Maladies vasculaires pulmonaires" de la Société de pneumologie de langue française.

Activity-based financing (that is, casemix-based hospital payments, known as T2A) is intended to harmonize and improve the fairness of remuneration of public and private hospitals. T2A will ultimately rely mainly on a flat rate per admission, set according to the diagnosis-related group (DRG). Although payment for drugs is usually included in the DRG price, some expensive drugs will be reimbursed on an additional cost basis after implementation of a "best practices" agreement. Four drugs used for treatment of pulmonary arterial hypertension are eligible for this additional reimbursement: 3 prostacyclin derivatives (intravenous epoprostenol, inhaled iloprost, and subcutaneous treprostinil), and oral bosentan, an endothelin receptor antagonist. The Pulmonary Vascular Diseases working group of the French Society of Pulmonary Medicine has developed guidelines for the best practices in use of these drugs.

Cost implications of using inhaled nitric oxide compared with epoprostenol for pulmonary hypertension.

OBJECTIVE: To compare the cost of using intravenous epoprostenol with that of inhaled nitric oxide (NO) for treating episodes of pulmonary hypertension in children with congenital heart disease. DESIGN: An analysis of the cost of epoprostenol and NO use over the previous 18 months was performed. Three 6-month periods were identified, two in which epoprostenol was used and the third in which inhaled NO was introduced for the treatment of pulmonary hypertension. SETTING: A 10-bed pediatric cardiac intensive care unit, Royal Liverpool Children's Hospital, Alder Hey, Liverpool, England. SUBJECTS: Children with congenital heart disease and persistently elevated pulmonary artery pressure following cardiac surgery. MAIN OUTCOME MEASURES: The total duration of use of epoprostenol and inhaled NO was documented. The costs per hour for epoprostenol and inhaled NO were calculated and the annual cost of each agent was estimated. RESULTS: In the two 6-month periods prior to the introduction of inhaled NO, epoprostenol was used on 14 occasions (5 in the first period, 3 in the second). In the last 6-month period, nine children required pulmonary vasodilator therapy on 14 occasions. All nine children were treated successfully with inhaled NO; none were given or needed epoprostenol, as NO always was effective in providing pulmonary vasodilatation. For resistant pulmonary hypertension, increasing the concentration of NO would have been the next therapeutic option. The cost for the two 6-month periods using epoprostenol was $19,483.48 for the drug and $283.25 for equipment costs (total cost $19,766.73). There was no expenditure on epoprostenol in the final 6-month period. The cost of NO was $465. However, the total expenditure, including the delivery and monitoring system, was $4,722.85. CONCLUSIONS: Using inhaled NO in our pediatric cardiac intensive care unit abolished the use of epoprostenol during the reported monitoring period. The cost savings were significant, amounting to 12% of the annual drug budget for the unit. The cost of setting up the inhaled NO delivery system is recouped rapidly. The ease of delivery and measurement of inhaled NO also may have contributed to its increased clinical use.