Surfactant status assessment and personalized therapy for surfactant deficiency or dysfunction.

Surfactant is a pivotal neonatal drug used both for respiratory distress syndrome due to surfactant deficiency and for more complex surfactant dysfunctions (such as in case of neonatal acute respiratory distress syndrome). Despite its importance, indications for surfactant therapy are often based on oversimplified criteria. Lung biology and modern monitoring provide several diagnostic tools to assess the patient surfactant status and they can be used for a personalized surfactant therapy. This is desirable to improve the efficacy of surfactant treatment and reduce associated costs and side effects. In this review we will discuss these diagnostic tools from a pathophysiological and multi-disciplinary perspective, focusing on the quantitative or qualitative surfactant assays, lung mechanics or aeration measurements, and gas exchange metrics. Their biological and technical characteristics are described with practical information for clinicians. Finally, available evidence-based data are reviewed, and the diagnostic accuracy of the different tools is compared. Lung ultrasound seems the most suitable tool for assessing the surfactant status, while some other promising tests require further research and/or development.

Comparing the clinical and economic efficiency of four natural surfactants in treating infants with respiratory distress syndrome.

Surfactant therapy has revolutionized the treatment of respiratory distress syndrome (RDS) over the past few decades. Relying on a new method, the current research seeks to compare four common surfactants in the health market of Iran to determine the best surfactant according to the selected criteria. The research was a cross-sectional, retrospective study that used the data of 13,169 infants as recorded on the information system of the Iranian Ministry of Health. To rank the surfactants used, the following indicators were measured: re-dosing rate, average direct treatment cost, average length of stay, disease burden, need for invasive mechanical ventilation, survival at discharge, and medical referrals. The CRITIC (criteria importance through intercriteria correlation) method was used to determine the weight of the indicators, and MABAC (multi-attributive border approximation area comparison) was used to prioritize the surfactants. Based on the seven selected indicators in this research (re-dosing rate, average length of stay, direct medical cost per one prescription, medical referral rate, survival at discharge, disability-adjusted life years, number of newborns in need of invasive mechanical ventilation) and using multi-criteria analysis method, Alveofact was identified as the worst surfactant in infants with either more or less than 32 weeks' gestation. So that some criteria were worse in Alveofact group infants than other groups; for example, in the comparison of the Alveofact group with the average of the total population, it was found that the survival rate at discharge was 57.14% versus 66.43%, and the rate of re-dosing was 1.63 versus 1.39. BLES (bovine lipid extract surfactant) was the best alternative for infants more than 32 weeks' gestation, whereas Survanta was identified as best option for infants with less than 32 weeks' gestation. Curosurf showed an average level of functionality in the ranking. This study advises the policy makers in the field of neonatal health to increase the market share of more effective surfactants based on this study and other similar studies. On the other hand, neonatal health care providers are also advised to prioritize the use of more effective surfactants if possible, depending on the clinical conditions and desired improvements.

Assessment of Comfort during Less Invasive Surfactant Administration in Very Preterm Infants: A Multicenter Study.

INTRODUCTION: This study was set up to investigate if and to what extent non-pharmacological analgesia is able to provide comfort to very preterm infants (VPI) during less invasive surfactant administration (LISA). METHODS: This was a prospective non-randomized multicenter observational study performed in level IV NICUs. Inborn VPI with a gestational age between 220/7 and 316/7 weeks, signs of respiratory distress syndrome, and the need for surfactant replacement were included. Non-pharmacological analgesia was performed in all infants during LISA. In case of failure of the first LISA attempt, additional analgosedation could be administered. COMFORTneo scores during LISA were assessed. RESULTS: 113 VPI with a mean gestational age of 27 weeks (+/- 2.3 weeks) and mean birth weight of 946 g (+/- 33 g) were included. LISA was successful at the first laryngoscopy attempt in 81%. COMFORTneo scores were highest during laryngoscopy. At this time point, non-pharmacological analgesia provided adequate comfort in 61% of the infants. 74.4% of lower gestational aged infants (i.e., 220-266 weeks) were within the comfort zone during laryngoscopy compared to 51.6% of higher gestational aged infants (i.e., 270-320 weeks) (p = 0.016). The time point of surfactant administration did not influence the COMFORTneo scores during the LISA procedure. CONCLUSION: Non-pharmacological analgesia provided comfort in as much as 61% of the included VPI during LISA. Further research is needed to both develop strategies to identify infants who, despite receiving non-pharmacological analgesia, are at high risk for experiencing discomfort during LISA and define patient-tailored dosage and choice of analgosedative drugs.

Cost-saving effect of early less invasive surfactant administration versus continuous positive airway pressure therapy alone for preterm infants with respiratory distress syndrome.

OBJECTIVES: Early rescue surfactant therapy using less invasive surfactant administration (LISA) can reduce the need for mechanical ventilation and avoid complications in preterm infants with respiratory distress syndrome. The purpose of this study was to estimate the budget impact of LISA compared with management based on continuous positive airway pressure (CPAP) alone and rescue surfactant therapy in case of CPAP failure. METHODS: A budget impact model was built comparing LISA with CPAP alone in order to estimate the potential resource consumption and budget impact from the perspective of the National Health Service in England. A literature review was conducted to populate the model. Deterministic and probabilistic sensitivity analyses were conducted to characterise the existing uncertainty and to explore the contribution of individual model parameters to the overall budget impact. RESULTS: Early rescue with LISA is expected to reduce resource consumption and costs compared with conservative therapy based on CPAP alone for preterm infants born at 25-32 weeks gestation. Savings are higher for preterm infants of 25-28 weeks (expected budget impact -£5146 per case, 95% credible interval (CrI) -£22 403 to £13, probability of being cost saving 97.4%) than for preterm infants of 29-32 weeks (-£176, 95% CrI -£4279 to £339, probability of being cost saving 85%). The impact of bronchopulmonary dysplasia (BPD) and intraventricular haemorrhage on resource consumption and the expected reduction in the incidence of BPD with LISA are the most influential parameters on the budget. CONCLUSIONS: Early rescue with LISA used in preterm infants with respiratory distress syndrome and fraction of inspired oxygen ≥0.3 is expected to be cost saving compared with management based on CPAP alone, particularly in those born at 25-28 weeks gestation.

Pharmaceutical Expenditure Is Unchanged with Ultrasound-Guided Surfactant Administration.

OBJECTIVE: Semiquantitative lung ultrasound improves the timeliness of surfactant replacement, but its financial consequences are unknown. We aim to investigate if the ultrasound-guided surfactant administration influences the general costs of surfactant therapy for preterm neonates affected by respiratory distress syndrome. STUDY DESIGN: This is a pharmacoeconomic, retrospective, and before-and-after study investigating the impact of ultrasound-guided surfactant replacement (echography-guided Surfactant THERapy [ESTHER]) on pharmaceutical expenditure within the ESTHER initiative. Data extracted from the institutional official database hosted by the hospital administration for financial management were used for the analysis. We analyzed the number of surfactant administrations in neonates of gestational age ≤326/7 weeks, and the number of surfactant vials used from January 1, 2014 to June 30, 2014 (i.e., during the period of standard surfactant administration policy) and from July 1, 2016 to December 31, 2018 (that is during ESTHER policy). RESULTS: ESTHER did not modify surfactant use, as proportion of treated neonates with RDS receiving at least one surfactant dose (Standard: 21.3% vs. ESTHER: 20.9%; p = 0.876) or as proportion of used vials over the total number of vials opened for neonates of any gestational age (Standard: 37% vs. ESTHER: 35%; p = 0.509). CONCLUSION: Ultrasound-guided surfactant replacement using a semiquantitative lung ultrasound score in preterm infants with RDS does not change the global use of surfactant and the related expenditure. KEY POINTS: · ESTHER is able to increase the timeliness of surfactant replacement.. · The ultrasound-guided surfactant administration does not increase the cost of surfactant therapy.. · The ultrasound-guided surfactant administration does not change the global surfactant utilization..

Pharmacoeconomic evaluation of different doses of Curosurf for treating neonatal acute respiratory distress syndrome.

Neonatal acute respiratory distress syndrome (ARDS) is a serious stage of acute lung injury (ALI) which can be treated by exogenous surfactant. The aim of this study was to explore the clinical efficacy of two different doses of Poractant alfa (Curosurf®) for treating neonatal ARDS and to perform an economic evaluation. Fifty-four patients were divided into Group A (high dose) and Group B (low dose). Pharmacoeconomic evaluation was performed on the two groups regarding the treatment expenses, and the output was the cure rate and complication rate. There were significant differences between Group A and Group B for the duration of receiving oxygen therapy in moderate cases (6.4±3.5d:8.9±2.6d) (P<0.05) and severe cases (10.0±2.6d:14.8±1.3d) (P<0.05). There were significant differences between them for the duration of undergoing mechanical ventilation in severe cases (1.7±2.3d:5.5±2.4d) (P=0.01). There was a significant difference between Group A and Group B for hospitalization expenses in severe cases (P<0.05). There were no significant differences between them in all types of cases for the cure rate (P>0.05). A high dose of Curosurf had an advantage in treating neonatal ARDS, especially in severe cases, with lower final costs and better effects.

Quality assessment and response to less invasive surfactant administration (LISA) without sedation.

BACKGROUND: Although sedative premedication for endotracheal intubation is considered standard of care, less invasive surfactant administration (LISA) is often performed without sedative premedication. The aim of this study was to assess success rates, technical quality and vital parameters in LISA without sedative premedication. METHODS: Prospective observational study in 86 neonates <32 weeks' gestation. LISA was performed according to a standardized protocol without use of sedative premedication. Outcome measures were success rates of LISA attempts, reasons for failure and quality of technical conditions. In 37 neonates, heart rate and oxygen saturation levels from 20 min before until 30 min after start of LISA were collected. RESULTS: In 48% of LISAs the first attempt failed and in 34% quality of technical conditions was inadequate. The success rate was significantly correlated with quality of technical conditions and experience of the performer. Desaturations <80% occurred in 54% of patients while bradycardia <80/min did not occur. CONCLUSION: This study shows a relatively low success rate of the first attempt of LISA, frequent inadequacy of technical quality and frequent oxygen desaturations. These effects may be improved by the use of sedative premedication.

Issues, challenges, and the way forward in conducting clinical trials among neonates: investigators' perspective.

Clinical trials are essential to test the safety and efficacy of new treatments in any population. The paucity of drug trials especially in the neonatal population has led to the widespread use of unlicensed or off-label medications, exposing them to the risks of drug toxicity and ineffective treatment. Ethical and operational challenges are no longer considered valid excuses for not conducting drug trials in neonates. We recently participated in a combined phase-2 and phase-3 trial investigating a new indigenous goat lung surfactant extract (GLSE) for the treatment of respiratory distress syndrome (RDS) in preterm neonates. In this article, we share pertinent challenges faced by us during the trial to better inform and foster-positive discussion among drug developers, administrators, regulatory authorities, patient advocacy groups, and researchers. Also, we provide many tools developed for the GLSE trial that can be modified and used by prospective trialists.

Clinical and Economic Analysis of Morphine Versus Fentanyl in Managing Ventilated Neonates With Respiratory Distress Syndrome in the Intensive Care Setting.

PURPOSE: Morphine and fentanyl opioids are common analgesic agents for consideration in the neonatal intensive care unit (NICU) for neonates with respiratory distress syndrome (RDS) and undergoing mechanical ventilation (MV). The aim of this study was to evaluate the clinical and economic impact of morphine versus fentanyl in neonates with RDS undergoing MV. METHODS: Retrospective cost-effectiveness analysis of critically ill neonates with RDS receiving standard doses of morphine versus fentanyl at Women's Wellness and Research Center, Qatar. Clinical data of neonates were extracted from medical records of patients from 2014 to 2016. A decision analytic model based on the hospital's perspective was constructed to follow possible consequences of the initial dosing of analgesia, before potential titration. Primary end points were successful pain relief rate based on the Premature Infant Pain Profile scale and overall direct medical cost of therapy. Study population of 126 neonates was used to achieve results with 80% power and 0.05 significance. Sensitivity analysis was conducted to enhance robustness of conclusions against input uncertainties and to increase generalizability of results. FINDINGS: Morphine achieved a success of 68% versus 43% with fentanyl (risk ratio = 1.72; 95% CI, 1.16-2.56; P = 0.0075). Morphine was associated with a minimal incremental cost-effectiveness ratio of USD 135 per additional case of successful pain relief over fentanyl. Higher morphine cost was reported in 2% of cases. Sensitivity analysis found model insensitivity to input uncertainties except NICU stay and cost of MV. IMPLICATIONS: This is the first cost-effectiveness evaluation of morphine versus fentanyl in the NICU. Morphine significantly improved the relieve of pain over fentanyl. It had 98% probability of dominance over fentanyl. Results in this study support the use of morphine over fentanyl as first-line monotherapy with MV in NICU settings.

Clinical, technological, and economic issues associated with developing new lung surfactant therapeutics.

Discovery of lung surfactant deficiency as a main cause of neonatal respiratory distress syndrome (NRDS) has influenced a steep increase in lung surfactant research. Although this has yielded impactful scientific discoveries, much of the basic research on lung surfactants has failed to translate into clinical practices. This is attributed to insufficient information covering the entire lung surfactant ecosystem, from the basic science to economics surrounding the development and clinical practices. In this manuscript, developments related to improving therapeutic lung surfactant as well as the degree of unmet need are analyzed from both technical and economic perspectives. Two potential opportunities are emphasized: (1) aerosolized lung surfactants to treat NRDS infants, and (2) synthetic lung surfactants for acute respiratory distress syndrome (ARDS) patients. Each has a modestly projected US market size of $120 million and $4 billion, well enough to make up for the high development costs associated with investigational drug development. Both opportunities have been pursued in the past, but to date these attempts have met with no success mainly due to technical limitations. With the recent advancements in both fields, technology improvements have created opportunities to solve both decades-old problems.

Efficacy and safety of surfactant replacement therapy for preterm neonates with respiratory distress syndrome in low- and middle-income countries: a systematic review.

Surfactant replacement therapy (SRT) has been shown to reduce mortality and air leaks in preterm neonates from high-income countries (HICs). The safety and efficacy of SRT in low- and middle- income countries (LMICs) have not been systematically evaluated. The major objectives of this review were to assess the (1) efficacy and safety, and (2) feasibility and cost effectiveness of SRT in LMIC settings. We searched the following databases-MEDLINE, CENTRAL, CINAHL, EMBASE and WHOLIS using the search terms 'surfactant' OR 'pulmonary surfactant'. Both experimental and observational studies that enrolled preterm neonates with or at-risk of respiratory distress syndrome (RDS) and required surfactant (animal-derived or synthetic) were included. A total of 38 relevant studies were found; almost all were from level-3 neonatal units. Pooled analysis of two randomized controlled trials (RCTs) and 22 observational studies showed a significant reduction in mortality at the last available time point in neonates who received SRT (relative risk (RR) 0.67; 95% confidence interval (CI) 0.57 to 0.79). There was also a significant reduction in the risk of air leaks (five studies; RR 0.51; 0.29 to 0.90). One RCT and twelve observational studies reported the risk of bronchopulmonary dysplasia (BPD) with contrasting results; while the RCT and most before-after/cohort studies showed a significant reduction or no effect, the majority of the case-control studies demonstrated significantly higher odds of receiving SRT in neonates who developed BPD. Two studies-one RCT and one observational-found no difference in the proportion of neonates developing pulmonary hemorrhage, while another observational study reported a higher incidence in those receiving SRT. The failure rate of the intubate-surfactant-extubate (InSurE) technique requiring mechanical ventilation or referral varied from 34 to 45% in four case-series. No study reported on the cost effectiveness of SRT. Available evidence suggests that SRT is effective, safe and feasible in level-3 neonatal units and has the potential to reduce neonatal mortality and air leaks in low-resource settings as well. However, there is a need to generate more evidence on the cost effectiveness of SRT and its effect on BPD in LMIC settings.

[Early use of calf pulmonary surfactant in late preterm and full-term infants with respiratory distress syndrome: a randomized controlled trial].

OBJECTIVE: To evaluate the efficacy of calf pulmonary surfactant (PS) in the treatment of respiratory distress syndrome (RDS) in late preterm and full-term infants. METHODS: A randomized controlled trial was designed to evaluate the efficacy of calf PS intratracheally given at different times and doses in infants with RDS who had a gestational age of ≥35 weeks and an oxygenation index (OI) of 10-20. The subjects were randomly assigned to treatment group 1 (n=58), treatment group 2 (n=58), and control group (n=59). Treatment group 1 was given PS (50 mg/kg) within 6 hours after admission. Treatment group 2 was given PS (70 mg/kg) within 6 hours after admission. The control group was not given PS within 6 hours after admission and was given PS (50 mg/kg) over 6 hours after admission if having no remission by conventional therapy including mechanical ventilation. For each group, a second dose of PS (50 mg/kg) was given if no remission was observed within 12 hours after the first administration. RESULTS: There were no significant differences in mortality between the three groups. Treatment group 2 had lower hospitalization expense and shorter duration of mechanical ventilation compared with treatment group 1, and treatment group 1 had lower hospitalization expense and shorter duration of mechanical ventilation compared with the control group. The incidence of ventilator-associated pneumonia and length of hospital stay in treatment group 2 was lower than those in treatment group 1 and control group. Compared with the control group, Treatment groups 1 and 2 showed decreases in 2 or more times of PS use, maximum OI, duration of continuous positive airway pressure treatment, and incidence of air leak syndrome and pulmonary hypertension. CONCLUSIONS: Early use of sufficient PS in late preterm and full-term infants with RDS can reduce complications, secondary use of PS, duration of mechanical ventilation and length of hospital stay, and hospitalization expense.

Economic evaluation of the use of exogenous pulmonary surfactants in preterm newborns in a Mexican population.

OBJECTIVE: To estimate the cost-effectiveness ratio of surfactant rescue treatment of premature infants with respiratory distress syndrome (RDS) who are covered by the Medical Insurance for a New Generation. MATERIALS AND METHODS: A cost-effectiveness evaluation was conducted from the third-payer perspective. Comparisons were made between the use of bovine surfactant (BS) therapy and without BS therapy. A decision tree model with a lifetime horizon was used where the measurements of effectiveness were life years gained (LYG) and quality-adjusted life years (QALYs). A 5% discount rate was considered for costs and health outcomes. All costs are expressed in Mexican pesos 2009. RESULTS: Incremental cost-effectiveness ratios (ICER) were MXN$136,670 per LYG and MXN$125,250 per QALY. CONCLUSION: Surfactant therapy was confirmed as a cost-effective strategy in accordance with World Health Organization criteria of three per capita gross domestic product (GDP) per QALY in premature infants with RDS in Mexico.

[Comparisons of efficacy of different pulmonary surfactants for the treatment of neonatal respiratory distress syndrome].

OBJECTIVE: To compare the clinical efficacy of imported pulmonary surfactant (PS) pig lung phospholipids injection (pig PS) and domestic cattle lung surface-active agent (cattle PS) for the treatment of neonatal respiratory distress syndrome (NRDS). METHODS: A total of 180 cases of grade IV NRDS receiving pig PS (n=90) or cattle PS treatment (n=90) were enrolled. The blood gas analysis and chest X-ray results and the incidence of complications after treatment, and hospitalization time and cost were compared between the two treatment groups. RESULTS: The efficiency rate in the pig PS group (97%) was higher than in the catle PS group (83%) (P<0.01). The cure rate in the pig PS group was also higher than in the cattle PS group (84% vs 66%; P<0.01). The incidence of pneumothorax in the pig PS group was lower than in the cattle PS group (3% vs 7%; P<0.05). The hospitalization time in the pig PS group was shorter than in the cattle PS group (21 ± 4 days vs 23 ± 4 days; P<0.05). There were no significant differences in the total hospitalization cost between the two groups. CONCLUSIONS: Pig PS seems to be superior to cattle PS in the treatment of grade IV NRDS.

Exploitations and their complications: the necessity of identifying the multiple forms of exploitation in pharmaceutical trials.

Human subject trials of pharmaceuticals in low and middle income countries (LMICs) have been associated with the moral wrong of exploitation on two grounds. First, these trials may include a placebo control arm even when proven treatments for a condition are in use in other (usually wealthier) parts of the world. Second, the trial researchers or sponsors may fail to make a successful treatment developed through the trial available to either the trial participants or the host community following the trial. Many commentators have argued that a single form of exploitation takes place during human subject research in LMICs. These commentators do not, however, agree as to what kind of moral wrong exploitation is or when exploitation is morally impermissible. In this paper, I have two primary goals. First, I will argue for a taxonomy of exploitation that identifies three distinct forms of exploitation. While each of these forms of exploitation has its critics, I will argue that they can each be developed into plausible accounts of exploitation tied to different vulnerabilities and different forms of wrongdoing. Second, I will argue that each of these forms of exploitation can coexist in single situations, including human subject trials of pharmaceuticals. This lesson is important, since different forms of exploitation in a single relationship can influence, among other things, whether the relationship is morally permissible.

Development of neonatal respiratory and intensive care: Chinese perspectives.

Recent economic improvements in China have allowed the development of perinatal-neonatal care in sub-provincial regions. However, variations in neonatal respiratory and intensive care exist, especially in regions with limited resources. We conducted a series of collaborative clinical investigations into neonatal hypoxemic respiratory failure (NRF). In the study period from 2004 to 2005, this nationwide study found an incidence of NRF of 13.4% of total admissions to neonatal intensive care units (NICUs), with a mortality of 32%. Fewer than 30% of infants with respiratory distress syndrome (RDS) received surfactant treatment. Most cases of NRF had birth weights (BWs) of 1,000-1,500 g. Approximately 60% of deaths were due to withdrawal of respiratory support because of economic restraints despite initial response to therapy. Extremely low BW or gestational age accounted for less than 2% of all NRF cases, and their survival rate was less than 50%. A prospective clinical epidemiologic study of NRF in 14 NICUs, mainly sub-provincial centers, in Hebei province was undertaken in the study period from 2007 to 2008. NRF made up 16.9% of total NICU admissions, with increased use of surfactant (>50%) and continuous positive airway pressure (>80%) in this study. However, mortality due to RDS, meconium aspiration syndrome and pulmonary infection/sepsis remained higher than 30%, in part affected by socioeconomic factors. With measures to assist hospitalized neonates from low income families in urban areas, as well as the 'new rural cooperative health care program' to subsidize families from rural areas, the quality and affordability of NICU services may be improved in the forthcoming years.

Economic evaluation of the use of exogenous pulmonary surfactants in preterm newborns in a Mexican population / Evaluación económica de la utilización de surfactantes pulmonares exógenos en recién nacidos pretérmino en población mexicana

OBJECTIVE: To estimate the cost-effectiveness ratio of surfactant rescue treatment of premature infants with respiratory distress syndrome (RDS) who are covered by the Medical Insurance for a New Generation. MATERIALS AND METHODS: A cost-effectiveness evaluation was conducted from the third-payer perspective. Comparisons were made between the use of bovine surfactant (BS) therapy and without BS therapy. A decision tree model with a lifetime horizon was used where the measurements of effectiveness were life years gained (LYG) and quality-adjusted life years (QALYs). A 5% discount rate was considered for costs and health outcomes. All costs are expressed in Mexican pesos 2009. RESULTS: Incremental cost-effectiveness ratios (ICER) were MXN$136670 per LYG and MXN$125250 per QALY. CONCLUSION: Surfactant therapy was confirmed as a cost-effective strategy in accordance with World Health Organization criteria of three per capita gross domestic product (GDP) per QALY in premature infants with RDS in Mexico.

OBJETIVO: Estimar la razón de costo efectividad incremental del tratamiento de surfactante de rescate en pacientes pretérmino con Síndrome de Dificultad Respiratoria (SDR) cubiertos por el Seguro Médico para una Nueva Generación. MATERIAL Y MÉTODOS: Evaluación de costo-efectividad desde la perspectiva del tercer pagador. Los comparadores fueron la terapia de surfactante bovino y la alternativa de no emplear ésta. Se utilizó un árbol de decisión que consideró la esperanza de vida como horizonte temporal y las medidas de efectividad fueron los años de vida ganados (AVG) y los años de vida ajustados por calidad de vida ( AVAC).Resultados en pesos mexicanos del 2009. RESULTADOS: Las RCEI por AVG y AVAC fueron de MXN$136670 y MXN$125250. CONCLUSIÓN: La razón de costo por AVG y AVAC para la terapia de surfactantes en pacientes prematuros con SDR en México fue menor a tres veces el PIB per cápita, por lo que es una estrategia costo-efectiva según los criterios de la OMS.

Increased Black-White disparities in mortality after the introduction of lifesaving innovations: a possible consequence of US federal laws.

OBJECTIVES: We explored whether the introduction of 3 lifesaving innovations introduced between 1989 and 1996 increased, decreased, or had no effect on disparities in Black-White mortality in the United States through 2006. METHODS: Centers for Disease Control and Prevention data were used to assess disease-, age-, gender-, and race-specific changes in mortality after the introduction of highly active anti-retroviral therapy (HAART) for treatment of HIV, surfactants for neonatal respiratory distress syndrome, and Medicare reimbursement of mammography screening for breast cancer. RESULTS: Disparities in Black-White mortality from HIV significantly increased after the introduction of HAART, surfactant therapy, and reimbursement for screening mammography. Between 1989 and 2006, these circumstances may have accounted for an estimated 22,441 potentially avoidable deaths among Blacks. CONCLUSIONS: These descriptive data contribute to the formulation of the hypothesis that federal laws promote increased disparities in Black-White mortality by inadvertently favoring Whites with respect to access to lifesaving innovations. Failure of legislation to address known social factors is a plausible explanation, at least in part, for the observed findings. Further research is necessary to test this hypothesis, including analytic epidemiological studies designed a priori to do so.

Surfactant replacement therapy.

Surfactant replacement therapy (SRT) has a proven role in the treatment of neonatal respiratory distress syndrome and severe meconium aspiration syndrome in infants, and may have a role in the treatment of pediatric patients with ARDS. Although newer delivery mechanisms and strategies are being studied, the classic surfactant administration paradigm consists of endotracheal intubation, surfactant instillation into the lung, and stabilization with mechanical ventilation followed by extubation when stable on low respiratory support. Currently, this surfactant administration procedure is bundled into Current Procedural Terminology (CPT) codes used when providing intensive care. A specific CPT code for surfactant administration is scheduled to be introduced in 2007. This article reviews clinical issues in SRT and the practice management considerations necessary to provide this care.

Cost effectiveness of prevention and treatment of neonatal respiratory distress (RDS) with exogenous surfactant: what has changed in the last three decades?

In 1993, exogenous surfactant products were emerging as licensed treatments for respiratory distress syndrome (RDS), a leading cause of death in preterm newborn babies. Models of cost-effectiveness of alternative treatments showed surfactant to be an expensive but effective and also cost effective treatment. However the most efficient policy for use of surfactant depended on other parallel 'technologies' such as giving antenatal corticosteroids where preterm delivery is anticipated. Following introduction into clinical practice, questions changed from whether to use surfactant, to when, and which product to use. The early models of cost effectiveness were dependent on the neonatal technology in use, and on the costs of neonatal care and prices of surfactant at the time. Little information was available about long term outcomes. The aims of this paper are to summarise the role of surfactant in the economics of newborn care since the late 1980s; to observe the value of studies published in the early 1990s for current decisions; and to comment on recent and possible future economic studies of neonatal surfactant.