Cost-effectiveness of nasal high-flow in children with acute hypoxaemic respiratory failure.

AIM: A pilot randomised controlled trial assessed the early application of nasal high-flow (NHF) therapy compared with standard oxygen therapy (SOT), in children aged 0 to 16 years presenting to paediatric emergency departments with acute hypoxaemic respiratory failure (AHRF). The study estimated the need to escalate therapy and hospital length of stay in the NHF group compared with SOT. This sub-study then assessed the subsequent cost-effectiveness. METHODS: A decision tree-based model was developed, alongside the clinical study, to estimate cost-effectiveness, from the healthcare sector perspective. The primary health economics outcome is measured as incremental cost per length of hospital stay avoided. Incremental cost effectiveness ratios (ICER) measuring change in cost per change in length of stay, were obtained for four samples, depending on responder status and obstructive airways disease. These were (1) obstructive and responder, (2) non-obstructive and responder, (3) obstructive and non-responder and (4) non obstructive and non-responder. Bootstrapping of parameters accounted for uncertainty in estimates of cost and outcome. RESULTS: The ICER for patients randomised to NHF, indicated an additional A$367.20 for a lower hospital length of stay (in days) in the non-obstructive/non-responder sample. In the bootstrap sample, this was found to be cost effective above a willingness to pay threshold of A$10 000. The ICER was A$440.86 in the obstructive/responder sample and A$469.56 in the non-obstructive/responder sample - but both resulted in a longer length of stay. The ICER in the obstructive/non-responder sample was A$52 167.76, also with a longer length of stay, mainly impacted by a small sample of severe cases. CONCLUSION: As first-line treatment, NHF is unlikely to be cost-effective compared with SOT, but for non-obstructive patients who required escalation in care (non-obstructive non-responder), NHF is likely to be cost-effective if willingness-to-pay per reduced hospital length of stay is more than A$10 000 per patient.

Usability Testing of a Reusable Pulse Oximeter Probe Developed for Health-Care Workers Caring for Children < 5 Years Old in Low-Resource Settings.

Hypoxemia measured by pulse oximetry predicts child pneumonia mortality in low-resource settings (LRS). Existing pediatric oximeter probes are prohibitively expensive and/or difficult to use, limiting LRS implementation. Using a human-centered design, we developed a low-cost, reusable pediatric oximeter probe for LRS health-care workers (HCWs). Here, we report probe usability testing. Fifty-one HCWs from Malawi, Bangladesh, and the United Kingdom participated, and seven experts provided reference measurements. Health-care workers and experts measured the peripheral arterial oxyhemoglobin saturation (SpO2) independently in < 5 year olds. Health-care worker measurements were classed as successful if recorded in 5 minutes (or shorter) and physiologically appropriate for the child, using expert measurements as the reference. All expert measurements were considered successful if obtained in < 5 minutes. We analyzed the proportion of successful SpO2 measurements obtained in < 1, < 2, and < 5 minutes and used multivariable logistic regression to predict < 1 minute successful measurements. We conducted four testing rounds with probe modifications between rounds, and obtained 1,307 SpO2 readings. Overall, 67% (876) of measurements were successful and achieved in < 1 minute, 81% (1,059) < 2 minutes, and 90% (1,181) < 5 minutes. Compared with neonates, increasing age (infant adjusted odds ratio [aOR]; 1.87, 95% confidence interval [CI]: 1.16, 3.02; toddler aOR: 4.33, 95% CI: 2.36, 7.97; child aOR; 3.90, 95% CI: 1.73, 8.81) and being asleep versus being calm (aOR; 3.53, 95% CI: 1.89, 6.58), were associated with < 1 minute successful measurements. In conclusion, we designed a novel, reusable pediatric oximetry probe that was effectively used by LRS HCWs on children. This probe may be suitable for LRS implementation.

Effectiveness, safety, and Economic Comparison of Two Inhaled Epoprostentol Products (Flolan and Veletri) in Cardiothoracic Surgery Patients.

BACKGROUND: No previous studies exist examining two inhaled epoprosternol formulations (Flolan compared with Veletri) in a homogenous cardiothoracic surgery patient population. OBJECTIVE: To compare the impact of inhaled Flolan and inhaled Veletri on the effectiveness, safety, or cost in cardiothoracic surgery patients. MATERIALS AND METHODS: This was a retrospective, noninferiority study comparing inhaled Flolan and inhaled Veletri in cardiothoracic surgery patients. Participants included were ≥18 years old, admitted to the cardiothoracic intensive care unit, and received inhaled Flolan or inhaled Veletri therapy for ≥1 hour. RESULTS: A total of 244 patients were included in the primary outcome analysis (122 patients per group). The primary outcome, change in the partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2/FiO2) ratio 1 hour after administration of inhaled Flolan or inhaled Veletri, did not cross the lower limit of the noninferiority margin (95% CI = -14.8 to 65.4). Significant differences in secondary outcomes included duration of mechanical ventilation (4.4 vs 2.6 days; P < 0.01), number of tracheostomies (24 vs 9; P = 0.01), number of patients initiated on dialysis (25 vs 12; P = 0.02), and cost per median duration of therapy ($257 vs $183; P = 0.02) in the inhaled Flolan and inhaled Veletri groups, with the average duration of therapy being 1.6 and 1.3 days, respectively. CONCLUSIONS AND RELEVANCE: Inhaled Veletri was demonstrated to be non-inferior to inhaled Flolan when comparing change in PaO2/FiO2 ratio 1 hour post -therapy initiation,and inhaled Veletri was an acceptable alternative to inhaled Flolan in a cardiothoracic surgery patient population.

A model for oxygen conservation associated with titration during pediatric oxygen therapy.

BACKGROUND: Continuous oxygen treatment is essential for managing children with hypoxemia, but access to oxygen in low-resource countries remains problematic. Given the high burden of pneumonia in these countries and the fact that flow can be gradually reduced as therapy progresses, oxygen conservation through routine titration warrants exploration. AIM: To determine the amount of oxygen saved via titration during oxygen therapy for children with hypoxemic pneumonia. METHODS: Based on published clinical data, we developed a model of oxygen flow rates needed to manage hypoxemia, assuming recommended flow rate at start of therapy, and comparing total oxygen used with routine titration every 3 minutes or once every 24 hours versus no titration. RESULTS: Titration every 3 minutes or every 24 hours provided oxygen savings estimated at 11.7% ± 5.1% and 8.1% ± 5.1% (average ± standard error of the mean, n = 3), respectively. For every 100 patients, 44 or 30 kiloliters would be saved-equivalent to 733 or 500 hours at 1 liter per minute. CONCLUSIONS: Ongoing titration can conserve oxygen, even performed once-daily. While clinical validation is necessary, these findings could provide incentive for the routine use of pulse oximeters for patient management, as well as further development of automated systems.

Solar-powered oxygen delivery: study protocol for a randomized controlled trial.

BACKGROUND: Pneumonia is a leading cause of childhood mortality globally. Oxygen therapy improves survival in children with pneumonia, yet its availability remains limited in many resource-constrained settings where most deaths occur. Solar-powered oxygen delivery could be a sustainable method to improve oxygen delivery in remote areas with restricted access to a supply chain of compressed oxygen cylinders and reliable electrical power. METHODS/DESIGN: This study is a randomized controlled trial (RCT). Solar-powered oxygen delivery systems will be compared to a conventional method (oxygen from cylinders) in patients with hypoxemic respiratory illness. Enrollment will occur at two sites in Uganda: Jinja Regional Referral Hospital and Kambuga District Hospital. The primary outcome will be the length of hospital stay. Secondary study endpoints will be mortality, duration of supplemental oxygen therapy (time to wean oxygen), proportion of patients successfully oxygenated, delivery system failure, cost, system maintenance and convenience. DISCUSSION: The RCT will provide useful data on the feasibility and noninferiority of solar-powered oxygen delivery. This technological innovation uses freely available inputs, the sun and the air, to oxygenate children with pneumonia, and can be applied "off the grid" in remote and/or resource-constrained settings where most pneumonia deaths occur. If proven successful, solar-powered oxygen delivery systems could be scaled up and widely implemented for impact on global child mortality. TRIAL REGISTRATION: Clinicaltrials.gov registration number NCT0210086 (date of registration: 27 March, 2014).

Peri-operative pulse oximetry in low-income countries: a cost-effectiveness analysis.

OBJECTIVE: To evaluate the cost-effectiveness of pulse oximetry--compared with no peri-operative monitoring--during surgery in low-income countries. METHODS: We considered the use of tabletop and portable, hand-held pulse oximeters among patients of any age undergoing major surgery in low-income countries. From earlier studies we obtained baseline mortality and the effectiveness of pulse oximeters to reduce mortality. We considered the direct costs of purchasing and maintaining pulse oximeters as well as the cost of supplementary oxygen used to treat hypoxic episodes identified by oximetry. Health benefits were measured in disability-adjusted life-years (DALYs) averted and benefits and costs were both discounted at 3% per year. We used recommended cost-effectiveness thresholds--both absolute and relative to gross domestic product (GDP) per capita--to assess if pulse oximetry is a cost-effective health intervention. To test the robustness of our results we performed sensitivity analyses. FINDINGS: In 2013 prices, tabletop and hand-held oximeters were found to have annual costs of 310 and 95 United States dollars (US$), respectively. Assuming the two types of oximeter have identical effectiveness, a single oximeter used for 22 procedures per week averted 0.83 DALYs per annum. The tabletop and hand-held oximeters cost US$ 374 and US$ 115 per DALY averted, respectively. For any country with a GDP per capita above US$ 677 the hand-held oximeter was found to be cost-effective if it prevented just 1.7% of anaesthetic-related deaths or 0.3% of peri-operative mortality. CONCLUSION: Pulse oximetry is a cost-effective intervention for low-income settings.

Characteristics and financial costs of patients with respiratory failure at bronchoscopy.

BACKGROUND: A case-control study was conducted to identify the possible risk factors for acute respiratory failure in patients undergoing bronchoscopy. We also aimed to estimate the financial costs incurred in the care of high-risk patients. METHODS: All hypoxic respiratory complications that occurred during bronchoscopy between January 2005 and March 2009 were reviewed. Mild hypoxia was defined as the need for up to 6 L of nasal cannula, moderate hypoxia as requiring up to 100% nonrebreather face mask, and severe hypoxia requiring intubation and mechanical ventilation to maintain pulse oximetry above 90%. The Wilcoxon 2-sample test was used to compare continuous groups. Categorical variables were assessed using χ(2), Fischer exact, and Kruskal-Wallis tests. We calculated the cost of medical care for patients admitted to the intensive care unit after bronchoscopy. RESULTS: During our study period, 26 patients were reported to have hypoxia with bronchoscopy. The mean age for our study group was 66.1 years, and body mass index 26.1 kg/m(2) (SD, 7.6). The study group's mean albumin was 2.9 g/dL (SD, 0.6) compared with 3.3 g/dL (SD, 0.7, P=0.0019), the study group's hematocrit was 32.4% (SD, 5.7) compared with 37.9% (SD, 5.5, P=0.0241), the study group's forced expiratory volume to forced vital capacity ratio ratio was 65.0 (SD, 15.8) compared with 78.0 (SD, 18.8, P=0.0133), and the study group's forced expiratory volume was 59.5% compared with 71.2% (P=0.0606). The study group's mean pCO(2) was 53.7 mm Hg (SD, 18.6). Six patients required intensive care unit admission after bronchoscopy and the total cost of care for this group was $80,353. CONCLUSIONS: Prescreening of selected patients may reduce respiratory failure and possibly the total cost of medical care.

Synthesis and biological evaluation of novel leonurine-SPRC conjugate as cardioprotective agents.

The synthesis and biological evaluation of novel leonurine-SPRC conjugate, 3,5-dimethoxy-4-(2-amino-3-prop-2-ynylsulfanyl-propionyl)-benzoic acid 4-guanidino-butyl ester (1) is reported in this Letter. It is designed to improve the pharmacology efficiency by combining leonurine with S-propargyl-L-cysteine (SPRC), a cysteine analog, via a phenolic hydroxyl ester bond, which could be readily hydrolyzed to release bioactive leonurine and SPRC. Pharmacological evaluation has shown that 1 possesses potent cardioprotective effect against hypoxia-induced neonatal rat ventricular myocytes damage at lower molar concentration (10-fold less than leonurine required and 100-fold less than SPRC required). The mechanism is in partial related to improve hydrogen sulfide production, anti-oxidative stress and anti-apoptosis.

Cost-effectiveness of exogenous surfactant therapy in pediatric patients with acute hypoxemic respiratory failure.

OBJECTIVE: To determine whether the use of exogenous surfactant (Infasurf) in pediatric acute hypoxemic respiratory failure is cost-effective. DESIGN: Deterministic cost-effectiveness analysis based on a Markov model. The model was calibrated using outcomes and resource utilization observed in a multiple-centered, prospective, randomized, controlled unblinded trial of Infasurf in pediatric acute hypoxemic respiratory failure. Costs were short-run direct costs estimated from the perspective of the hospital as provider. Primary outcomes were expected costs, expected survival rates, and incremental cost per life saved. SETTING: Patients in the trial were treated in one of eight pediatric intensive care units of tertiary medical centers. PATIENTS: Forty-two children with acute hypoxemic respiratory failure who were randomized to receive either standard therapy or exogenous surfactant in addition to standard therapy. MEASUREMENTS AND MAIN RESULTS: Our baseline analysis suggests that for a 10-kg child, the Infasurf strategy is both less costly (62,922 US dollars vs. 74,006 US dollars) and more effective (survival: 90.3% vs. 85.1%) and therefore dominates standard treatment. Cost savings were realized in the model because patients in the surfactant group were more likely to leave the pediatric intensive care unit sooner. The Infasurf strategy continues to dominate for children up to 60 kg. At 70 kg, the cost to save an additional life using the Infasurf strategy is 79,805 US dollars, which is still cost-effective if the provider is willing to make this tradeoff. CONCLUSIONS: For the majority of pediatric patients with acute hypoxemic respiratory failure, exogenous surfactant is cost-effective. If the use of this medication becomes standard care, a greater variety of packaging sizes could lead to decreased acquisition costs and increase the number of patients for whom this treatment is cost-effective.

Cost-effectiveness of inhaled nitric oxide in the treatment of neonatal respiratory failure in the United States.

OBJECTIVE: Two recent randomized controlled trials (RCTs) reported that inhaled nitric oxide (iNO) decreased the incidence of extracorporeal membrane oxygenation (ECMO) or death in term and near-term newborns with hypoxic respiratory failure. Our objective was to estimate the cost-effectiveness ratio of iNO in this population. METHODS: We studied 1000 simulation cohorts (n = 483 for each cohort) of term/near-term newborns with hypoxemic respiratory failure. We conducted our study following US Public Health Service Panel on Cost-Effectiveness in Health and Medicine guidelines, adopting the US societal perspective. We constructed a decision tree reflecting iNO use, subsequent ECMO use, death, and long-term neurologic and respiratory morbidity in survivors, as determined from the combined outcomes of the 2 RCTs (n = 483). We estimated costs on the basis of length-of-stay data for the initial episode of care from 1 of the RCTs, unit costs from administrative data sets, and current pricing for iNO. We ran a Monte Carlo simulation to generate estimates of differences in costs and effects at 1 year, along with the stochastic uncertainty around these estimates. We expressed effects as quality-adjusted survival, assuming quality of life = 1 with no comorbidity, 0.7 with 1 comorbidity, and 0.49 (0.7 x 0.7) with 2 comorbidities. We constructed a base case, in which iNO was initiated at tertiary care ECMO centers (mimicking the RCTs) and a Public Health Service Panel on Cost-effectiveness in Health and Medicine reference case, in which iNO was initiated at the local hospital before transfer (mimicking real-world practice). We exposed our assumptions to a sensitivity analysis. RESULTS: Direct application of the trial results (base case) suggested that iNO was both more effective and cheaper (cost savings of 1880 dollars per case despite acquisition costs of 5150 dollars, predominantly as a result of decreased need for ECMO), with 84.6% probability that the cost-effectiveness ratio was better than 100,000 dollars per quality-adjusted life-year. Under the reference case, iNO was also more effective (though slightly less so) and was even cheaper (cost savings of 4400 dollars per case), with 71.6% probability that iNO was cheaper and more effective and 91.6% probability that the cost effectiveness ratio was better than 100,000 dollars per quality-adjusted life-year. Sensitivity analyses showed these estimates to be sensitive to patient selection and the price of iNO but insensitive to assumptions regarding quality of life. CONCLUSIONS: From a US societal perspective, iNO has a favorable cost-effectiveness profile when initiated either at ECMO centers or at local hospitals in term/near-term neonates with hypoxemic respiratory failure.

Reengineering respiratory support following extubation: avoidance of critical care unit costs.

STUDY OBJECTIVE: We prospectively investigated alternative clinical practice strategies for critically ill trauma patients following extubation to evaluate the cost-effectiveness of these maneuvers. The primary change was elimination of the routine use of postextubation supplemental oxygen, with concurrent utilization of noninvasive positive pressure ventilatory support (NPPV) to manage occurrences of postextubation hypoxemia. DESIGN: Prospective, consecutive accrual of patients undergoing extubation. SETTING: Trauma ICU in a university hospital. INTERVENTIONS AND MEASUREMENTS: All patients received mechanical ventilation using pressure support ventilation (PSV) with continuous positive airway pressure (CPAP) as the primary mode. The patients were extubated to room air following a 20-min preextubation trial of 5 cm H(2)O CPAP at FIO(2) of 0.21, and demonstrating a spontaneous respiratory rate /= 7.30, PaCO(2) /= 50 mm Hg. The subgroup of patients who became hypoxemic (pulse oximetric saturation < 88%) within 24 h of extubation were treated with NPPV for up to 48 h duration. Patients who failed NPPV were reintubated. Four hundred fifty-one (84%) patients were successfully extubated to room air. Seventy-two patients (13%) became hypoxemic within 24 h, and NPPV was administered. Fifty-two patients (72% of those who were hypoxemic) responded to NPPV, while 20 patients failed to respond to therapy, were reintubated, and received mechanical ventilation for a mean of 4 days. Thirteen additional patients (2%) were reintubated for reasons other than hypoxemia. The overall reintubation rate for the group (n = 536) was 6.2%; for the postextubation hypoxemic group who failed NPPV, the reintubation rate was 3.7%. The elimination of routine supplemental oxygen via nasal cannula following extubation resulted in a potential direct cost avoidance of $50,006.88 for 451 patient days. Moreover, the 52 patients who were spared reintubation and mechanical ventilation provided an additional potential cost avoidance of $19,740.24 in unused ventilator days per patient. CONCLUSION: Eliminating the routine use of supplemental oxygen and employing NPPV as a method to prevent reintubation can facilitate a more aggressive, cost-effective strategy for the management of the trauma ICU patient who has been extubated.

[Long-term home oxygen therapy: who? with what? how expensive?]. / Langfristige Sauerstoffheimtherapie: Wer? Womit? Wie teuer?

Since 1981 long-term oxygen therapy (LTOT) has become an important procedure for the rehabilitation of patients with chronic respiratory insufficiency in Switzerland too. As a result of long-term clinical experience as well as technical progress, there is, however, increasing need for an updated reassessment of guidelines and standardized management respectively: the indications for LTOT-so far restricted to patients with COPD-are extended to patients with pulmonary diseases other than COPD associated with chronic hypoxemia (pO2 < 7.3 kPa) provided there is enough evidence of clinical benefit. Another important aspect of LTOT focuses on the appropriate application of different oxygen sources. Oxygen concentrators are still accepted to be the most economic domiciliary source. For short-term outdoor activities, small portable cylinders in combination with an oxygen conserving system should be used. However, in regular mobile oxygen therapy liquid oxygen is the best choice, generally consisting of a domiciliary reservoir and portable canisters. Delivery of oxygen through a transtracheal catheter is superior to nasal cannula because of lower oxygen consumption, decreased breathing work and improved compliance respectively. To organize and follow-up LTOT in Switzerland, a very efficient concept was introduced many years ago which is characterized by economical cooperation between physicians, insurances, technical suppliers and social providers. Today more than 3000 patients-corresponding to 38/100,000 inhabitants-benefit from LTOT. Future perspectives should target an earlier start to continuous as well as mobile LTOT, in order to improve rehabilitation in still active conditions instead of merely palliating the terminal stages.

Domiciliary liquid oxygen versus concentrator treatment in chronic hypoxaemia: a cost-utility analysis.

Whether long-term oxygen therapy (LTOT) improves quality of life in chronic hypoxaemia has been questioned. LTOT with an oxygen concentrator (C/C) and gas cylinders for ambulation is considered cumbersome compared to mobile liquid oxygen equipment (L). The hypothesis for this study was that LTOT with liquid oxygen treatment (L) improves patients' health-related quality of life, but that it is also more expensive compared to concentrator (C/C) treatment. A prospective, randomized multicentre trial comparing C/C with L for LTOT was conducted during a six-month period. Fifty-one patients (29 on L and 22 on C/C) with chronic hypoxaemia, regularly active outside the home, participated in the study initially. Costs for oxygen were obtained from the pharmacies. Patient diaries and telephone contacts with members of the healthcare sector were used to estimate costs. Health-related quality of life was measured by the Sickness Impact Profile (SIP) and the EuroQol, instruments at the start and after 6 months. The average total cost per patient for group C/C for the six-month period was US$1,310, and for group L it was US$4,950. Health-related quality of life measured by the SIP instrument showed significant differences in favour of group L in the categories/dimensions of physical function, body care, ambulation, social interaction and total SIP score. In conclusion, liquid-oxygen treatment was more expensive compared to concentrator treatment. However, treatment effects showed that liquid oxygen had a better impact on quality of life.