Cost-effectiveness of low-dose aspirin for the prevention of preterm birth: a prospective study of the Global Network for Women's and Children's Health Research.

BACKGROUND: Premature birth is associated with an increased risk of mortality and morbidity, and strategies to prevent preterm birth are few in number and resource intensive. In 2020, the ASPIRIN trial showed the efficacy of low-dose aspirin (LDA) in nulliparous, singleton pregnancies for the prevention of preterm birth. We sought to investigate the cost-effectiveness of this therapy in low-income and middle-income countries. METHODS: In this post-hoc, prospective, cost-effectiveness study, we constructed a probabilistic decision tree model to compare the benefits and costs of LDA treatment compared with standard care using primary data and published results from the ASPIRIN trial. In this analysis from a health-care sector perspective, we considered the costs and effects of LDA treatment, pregnancy outcomes, and neonatal health-care use. We did sensitivity analyses to understand the effect of the price of the LDA regimen, and the effectiveness of LDA in reducing both preterm birth and perinatal death. FINDINGS: In model simulations, LDA was associated with 141 averted preterm births, 74 averted perinatal deaths, and 31 averted hospitalisations per 10 000 pregnancies. The reduction in hospitalisation resulted in a cost of US$248 per averted preterm birth, $471 per averted perinatal death, and $15·95 per disability-adjusted life year. INTERPRETATION: LDA treatment in nulliparous, singleton pregnancies is a low-cost, effective treatment to reduce preterm birth and perinatal death. The low cost per disability-adjusted life year averted strengthens the evidence in support of prioritising the implementation of LDA in publicly funded health care in low-income and middle-income countries. FUNDING: Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Derivation and validation of a novel risk assessment tool to identify children aged 2-59 months at risk of hospitalised pneumonia-related mortality in 20 countries.

INTRODUCTION: Existing risk assessment tools to identify children at risk of hospitalised pneumonia-related mortality have shown suboptimal discriminatory value during external validation. Our objective was to derive and validate a novel risk assessment tool to identify children aged 2-59 months at risk of hospitalised pneumonia-related mortality across various settings. METHODS: We used primary, baseline, patient-level data from 11 studies, including children evaluated for pneumonia in 20 low-income and middle-income countries. Patients with complete data were included in a logistic regression model to assess the association of candidate variables with the outcome hospitalised pneumonia-related mortality. Adjusted log coefficients were calculated for each candidate variable and assigned weighted points to derive the Pneumonia Research Partnership to Assess WHO Recommendations (PREPARE) risk assessment tool. We used bootstrapped selection with 200 repetitions to internally validate the PREPARE risk assessment tool. RESULTS: A total of 27 388 children were included in the analysis (mean age 14.0 months, pneumonia-related case fatality ratio 3.1%). The PREPARE risk assessment tool included patient age, sex, weight-for-age z-score, body temperature, respiratory rate, unconsciousness or decreased level of consciousness, convulsions, cyanosis and hypoxaemia at baseline. The PREPARE risk assessment tool had good discriminatory value when internally validated (area under the curve 0.83, 95% CI 0.81 to 0.84). CONCLUSIONS: The PREPARE risk assessment tool had good discriminatory ability for identifying children at risk of hospitalised pneumonia-related mortality in a large, geographically diverse dataset. After external validation, this tool may be implemented in various settings to identify children at risk of hospitalised pneumonia-related mortality.

Improving the experience of facility-based delivery for vulnerable women through obstetric care navigation: a qualitative evaluation.

BACKGROUND: Global disparities in maternal mortality could be reduced by universal facility delivery. Yet, deficiencies in the quality of care prevent some mothers from seeking facility-based obstetric care. Obstetric care navigators (OCNs) are a new form of lay health workers that combine elements of continuous labor support and care navigation to promote obstetric referrals. Here we report qualitative results from the pilot OCN project implemented in Indigenous villages in the Guatemalan central highlands. METHODS: We conducted semi-structured interviews with 17 mothers who received OCN accompaniment and 13 staff-namely physicians, nurses, and social workers-of the main public hospital in the pilot's catchment area (Chimaltenango). Interviews queried OCN's impact on patient and hospital staff experience and understanding of intended OCN roles. Audiorecorded interviews were transcribed, coded, and underwent content analysis. RESULTS: Maternal fear of surgical intervention, disrespectful and abusive treatment, and linguistic barriers were principal deterrents of care seeking. Physicians and nurses reported cultural barriers, opposition from family, and inadequate hospital resources as challenges to providing care to Indigenous mothers. Patient and hospital staff identified four valuable services offered by OCNs: emotional support, patient advocacy, facilitation of patient-provider communication, and care coordination. While patients and most physicians felt that OCNs had an overwhelmingly positive impact, nurses felt their effort would be better directed toward traditional nursing tasks. CONCLUSIONS: Many barriers to maternity care exist for Indigenous mothers in Guatemala. OCNs can improve mothers' experiences in public hospitals and reduce limitations faced by providers. However, broader buy-in from hospital staff-especially nurses-appears critical to program success. Future research should focus on measuring the impact of obstetric care navigation on key clinical outcomes (cesarean delivery) and mothers' future care seeking behavior.

Maternal mortality in six low and lower-middle income countries from 2010 to 2018: risk factors and trends.

BACKGROUND: Maternal mortality is a public health problem that disproportionately affects low and lower-middle income countries (LMICs). Appropriate data sources are lacking to effectively track maternal mortality and monitor changes in this health indicator over time. METHODS: We analyzed data from women enrolled in the NICHD Global Network for Women's and Children's Health Research Maternal Newborn Health Registry (MNHR) from 2010 through 2018. Women delivering within research sites in the Democratic Republic of Congo, Guatemala, India (Nagpur and Belagavi), Kenya, Pakistan, and Zambia are included. We evaluated maternal and delivery characteristics using log-binomial models and multivariable models to obtain relative risk estimates for mortality. We used running averages to track maternal mortality ratio (MMR, maternal deaths per 100,000 live births) over time. RESULTS: We evaluated 571,321 pregnancies and 842 maternal deaths. We observed an MMR of 157 / 100,000 live births (95% CI 147, 167) across all sites, with a range of MMRs from 97 (76, 118) in the Guatemala site to 327 (293, 361) in the Pakistan site. When adjusted for maternal risk factors, risks of maternal mortality were higher with maternal age > 35 (RR 1.43 (1.06, 1.92)), no maternal education (RR 3.40 (2.08, 5.55)), lower education (RR 2.46 (1.54, 3.94)), nulliparity (RR 1.24 (1.01, 1.52)) and parity > 2 (RR 1.48 (1.15, 1.89)). Increased risk of maternal mortality was also associated with occurrence of obstructed labor (RR 1.58 (1.14, 2.19)), severe antepartum hemorrhage (RR 2.59 (1.83, 3.66)) and hypertensive disorders (RR 6.87 (5.05, 9.34)). Before and after adjusting for other characteristics, physician attendance at delivery, delivery in hospital and Caesarean delivery were associated with increased risk. We observed variable changes over time in the MMR within sites. CONCLUSIONS: The MNHR is a useful tool for tracking MMRs in these LMICs. We identified maternal and delivery characteristics associated with increased risk of death, some might be confounded by indication. Despite declines in MMR in some sites, all sites had an MMR higher than the Sustainable Development Goals target of below 70 per 100,000 live births by 2030. TRIAL REGISTRATION: The MNHR is registered at NCT01073475 .

Development of the Global Network for Women's and Children's Health Research's socioeconomic status index for use in the network's sites in low and lower middle-income countries.

BACKGROUND: Socioeconomic status (SES) is an important determinant of health globally and an important explanatory variable to assess causality in epidemiological research. The 10th Sustainable Development Goal is to reduce disparities in SES that impact health outcomes globally. It is easier to study SES in high-income countries because household income is representative of the SES. However, it is well recognized that income is poorly reported in low- and middle- income countries (LMIC) and is an unreliable indicator of SES. Therefore, there is a need for a robust index that will help to discriminate the SES of rural households in a pooled dataset from LMIC. METHODS: The study was nested in the population-based Maternal and Neonatal Health Registry of the Global Network for Women's and Children's Health Research which has 7 rural sites in 6 Asian, sub-Saharan African and Central American countries. Pregnant women enrolling in the Registry were asked questions about items such as housing conditions and household assets. The characteristics of the candidate items were evaluated using confirmatory factor analyses and item response theory analyses. Based on the results of these analyses, a final set of items were selected for the SES index. RESULTS: Using data from 49,536 households of pregnant women, we reduced the data collected to a 10-item index. The 10 items were feasible to administer, covered the SES continuum and had good internal reliability and validity. We developed a sum score-based Item Response Theory scoring algorithm which is easy to compute and is highly correlated with scores based on response patterns (r = 0.97), suggesting minimal loss of information with the simplified approach. Scores varied significantly by site (p < 0.001). African sites had lower mean SES scores than the Asian and Central American sites. The SES index demonstrated good internal consistency reliability (Cronbach's alpha = 0.81). Higher SES scores were significantly associated with formal education, more education, having received antenatal care, and facility delivery (p < 0.001). CONCLUSIONS: While measuring SES in LMIC is challenging, we have developed a Global Network Socioeconomic Status Index which may be useful for comparisons of SES within and between locations. Next steps include understanding how the index is associated with maternal, perinatal and neonatal mortality. Trial Registration NCT01073475 Socioeconomic status (SES) is an important determinant of health globally, and improving SES is important to reduce disparities in health outcomes. It is easier to study SES in high-income countries because it can be measured by income and what income is spent on, but this concept does not translate easily to low and middle income countries. We developed a questionnaire that includes 10 items to determine SES in low-resource settings that was added to an ongoing Maternal and Neonatal Health Registry that is funded by the National Institutes of Child Health and Human Development's Global Network. The Registry includes sites that collect outcomes of pregnancies in women and their babies in rural areas in 6 countries in South Asia, sub-Saharan Africa and Central America. The Registry is population based and tracks women from early in pregnancy to day 42 post-partum. The questionnaire is easy to administer and has good reliability and validity. Next steps include understanding how the index is associated with maternal, fetal and neonatal mortality.

Data quality monitoring and performance metrics of a prospective, population-based observational study of maternal and newborn health in low resource settings.

BACKGROUND: To describe quantitative data quality monitoring and performance metrics adopted by the Global Network's (GN) Maternal Newborn Health Registry (MNHR), a maternal and perinatal population-based registry (MPPBR) based in low and middle income countries (LMICs). METHODS: Ongoing prospective, population-based data on all pregnancy outcomes within defined geographical locations participating in the GN have been collected since 2008. Data quality metrics were defined and are implemented at the cluster, site and the central level to ensure data quality. Quantitative performance metrics are described for data collected between 2010 and 2013. RESULTS: Delivery outcome rates over 95% illustrate that all sites are successful in following patients from pregnancy through delivery. Examples of specific performance metric reports illustrate how both the metrics and reporting process are used to identify cluster-level and site-level quality issues and illustrate how those metrics track over time. Other summary reports (e.g. the increasing proportion of measured birth weight compared to estimated and missing birth weight) illustrate how a site has improved quality over time. CONCLUSION: High quality MPPBRs such as the MNHR provide key information on pregnancy outcomes to local and international health officials where civil registration systems are lacking. The MNHR has measures in place to monitor data collection procedures and improve the quality of data collected. Sites have increasingly achieved acceptable values of performance metrics over time, indicating improvements in data quality, but the quality control program must continue to evolve to optimize the use of the MNHR to assess the impact of community interventions in research protocols in pregnancy and perinatal health. TRIAL REGISTRATION NUMBER: NCT01073475.

Postpartum contraceptive use and unmet need for family planning in five low-income countries.

BACKGROUND: During the post-partum period, most women wish to delay or prevent future pregnancies. Despite this, the unmet need for family planning up to a year after delivery is higher than at any other time. This study aims to assess fertility intention, contraceptive usage and unmet need for family planning amongst women who are six weeks postpartum, as well as to identify those at greatest risk of having an unmet need for family planning during this period. METHODS: Using the NICHD Global Network for Women's and Children's Health Research's multi-site, prospective, ongoing, active surveillance system to track pregnancies and births in 100 rural geographic clusters in 5 countries (India, Pakistan, Zambia, Kenya and Guatemala), we assessed fertility intention and contraceptive usage at day 42 post-partum. RESULTS: We gathered data on 36,687 women in the post-partum period. Less than 5% of these women wished to have another pregnancy within the year. Despite this, rates of modern contraceptive usage varied widely and unmet need ranged from 25% to 96%. Even amongst users of modern contraceptives, the uptake of the most effective long-acting reversible contraceptives (intrauterine devices) was low. Women of age less than 20 years, parity of two or less, limited education and those who deliver at home were at highest risk for having unmet need. CONCLUSIONS: Six weeks postpartum, almost all women wish to delay or prevent a future pregnancy. Even in sites where early contraceptive adoption is common, there is substantial unmet need for family planning. This is consistently highest amongst women below the age of 20 years. Interventions aimed at increasing the adoption of effective contraceptive methods are urgently needed in the majority of sites in order to reduce unmet need and to improve both maternal and infant outcomes, especially amongst young women. STUDY REGISTRATION: Clinicaltrials.gov (ID# NCT01073475).

Institutional deliveries and perinatal and neonatal mortality in Southern and Central India.

BACKGROUND: Skilled birth attendance and institutional delivery have been advocated for reducing maternal, perinatal and neonatal mortality (PMR and NMR). India has successfully implemented various strategies to promote skilled attendance and incentivize institutional deliveries in the last 5 years. OBJECTIVES: The study evaluates the trends in institutional delivery, PMR, NMR, and their risk factors in two Eunice Kennedy Shriver NICHD Global Network for Women's and Children's Health Research sites, in Belgaum and Nagpur, India, between January 2010 and December 2013. DESIGN/METHODS: Descriptive data stratified by level of delivery care and key risk factors were analyzed for 36 geographic clusters providing 48 months of data from a prospective, population-based surveillance system that registers all pregnant permanent residents in the study area, and their pregnancy outcomes irrespective of where they deliver. Log binomial models with generalized estimating equations to control for correlation of clustered observations were used to test the trends significance RESULTS: 64,803 deliveries were recorded in Belgaum and 39,081 in Nagpur. Institutional deliveries increased from 92.6% to 96.1% in Belgaum and from 89.5% to 98.6% in Nagpur (both p<0.0001); hospital rates increased from 63.4% to 71.0% (p=0.002) and from 63.1% to 72.0% (p<0.0001), respectively. PMR declined from 41.3 to 34.6 (p=0.008) deaths per 1,000 births in Belgaum and from 47.4 to 40.8 (p=0.09) in Nagpur. Stillbirths also declined, from 22.5 to 16.3 per 1,000 births in Belgaum and from 29.3 to 21.1 in Nagpur (both p=0.002). NMR remained unchanged. CONCLUSIONS: Significant increases in institutional deliveries, particularly in hospitals, were accompanied by reductions in stillbirths and PMR, but not by NMR.

Consequences of household air pollution on child survival: evidence from demographic and health surveys in 47 countries.

BACKGROUND: Over one-third of the world's population is exposed to household air pollution (HAP) but the separate effects of cooking with solid fuel and kerosene on childhood mortality are unclear. OBJECTIVES: To evaluate the effects of both solid fuels and kerosene on neonatal (0-28 days) and child (29 days-59 months) mortality. METHODS: We used Demographic and Health Surveys from 47 countries and calculated adjusted relative risks (aRR) using Poisson regression models. RESULTS: The aRR of neonatal and child mortality in households exposed to solid fuels were 1.24 (95% CI: 1.14, 1.34) and 1.21 (95% CI: 1.12, 1.30), respectively, and the aRR for neonatal and child mortality in households exposed to kerosene were 1.34 (95% CI: 1.18, 1.52) and 1.12 (95% CI: 0.99, 1.27), controlling for individual, household, and country-level predictors of mortality. CONCLUSIONS: Kerosene should not be classified as a clean fuel. Neonates are at risk for mortality from exposure to solid fuels and kerosene.

Childhood illness in households using biomass fuels in India: secondary data analysis of nationally representative national family health surveys.

BACKGROUND: Half of the world's population uses solid fuels for energy and cooking, resulting in 1.5 million deaths annually, approximately one-third of which occur in India. Most deaths are linked to childhood pneumonia or acute lower respiratory tract infection (ALRI), conditions that are difficult to diagnose. The overall effect of biomass combustion on childhood illness is unclear. OBJECTIVES: To evaluate whether type of household fuel is associated with symptoms of ALRI (cough and difficulty breathing), diarrhea or fever in children aged 0-36 months. METHODS: We analyzed nationally representative samples of households with children aged 0-36 months from three national family health surveys conducted between 1992 and 2006 in India. Households were categorized as using low (liquid petroleum gas/electricity), medium (coal/kerosene) or high polluting fuel (predominantly wood/agricultural waste). Odds ratios adjusted for confounders for exposure to high and medium polluting fuel were compared with low polluting fuel (LPF). RESULTS: Use of high polluting fuel (HPF) in India changed minimally (82 to 78 %), although LPF use increased from 8% to 18%. HPF was consistently associated with ALRI [adjusted odds ratio (95% confidence interval) 1.48 (1.08-2.03) in 1992-3; 1.54 (1.33-1.77) in 1998-9; and 1.53 (1.21-1.93) in 2005-6). Fever was associated with HPF in the first two surveys but not in the third survey. Diarrhea was not consistently associated with HPF. CONCLUSIONS: There is an urgent need to increase the use of LPF or equivalent clean household fuel to reduce the burden of childhood illness associated with IAP in India.

Accuracy of a novel system for oxygen delivery to small children.

OBJECTIVE: Oxygen therapy for infants and small children in developing countries is often not available. Entrainment devices may provide an accurate and precise concentration of oxygen when used at the flow rates appropriate for infants and small children. METHODS: A continuously adjustable entrainment device was tested to determine the concentrations and flows of oxygen delivered by using low inlet flow rates suitable for therapy for infants and small children and 3 distinct oxygen delivery systems that varied in their resistive load. RESULTS: The use of long and large bore, low resistance tubing (similar to a mask) resulted in the delivery of oxygen concentrations that tracked closely (accurate and precise) to values indicated by the entrainment device. The directly connected system with lower resistance (similar to a hood) produced a similar profile of concentrations and flow rates to the large bore tubing but with even greater accuracy. The use of a long and narrow tubing with higher resistance (similar to a cannula) did not deliver accurate oxygen concentrations. In fact, this high-resistance system failed to work as intended, and instead of entraining air, a large proportion (sometimes >50%) of the oxygen delivered to the entrainment device was ejected through its vents. CONCLUSIONS: Entrainment devices can deliver accurate oxygen concentrations at low flow rates if used with low resistance delivery systems; however, entrainment devices are not suitable for use with high resistance delivery systems such as a standard nasal cannula.

Conducting drug abuse investigations in natural environments: potential directions for medical toxicology research.

Physician-scientists, in the eyes of the National Institutes of Health (NIH), are crucial to the biomedical research enterprise since the development of evidence-based practice based on cutting-edge research. At the same time, NIH has heightened the importance of research mentorship by permitting investigators to revise an application a single time. The current NIH approach, therefore, narrows the margin of error allowable in a proposal and requires that investigators fully develop research protocols for initial submission. The purpose of this manuscript, therefore, is to provide medical toxicologists with a proven research methodology that can be applied to substance abuse investigations. A secondary aim is to provide successful grant language that can be used in subsequent applications for research funding.

Monitoring participant safety in phase I and II interventional trials: options and controversies.

BACKGROUND: The need for phase I and II clinical trials to have a data and safety monitoring plan (DSMP) is widely accepted; however, whether and/or when these trials should also have oversight by a data and safety monitoring board (DSMB) is controversial. Monitoring requirements also depend on whether the study is funded by the National Institutes of Health, funded and/or monitored by the US Food and Drug Administration (FDA), or funded by industry. However, there is little guidance about when and how to constitute a DSMB for phase I and II clinical trials. OBJECTIVES: The objectives of this article are to suggest guidelines for when and how to constitute a DSMB for phase I and II studies and to highlight the similarities and differences between DSMBs monitoring phase I and II versus phase III clinical studies. We highlight the utility of these guidelines in the safety monitoring of a mechanism of disease-based study of inhaled nitric oxide for acute vaso-occlusive crisis in pediatric patients with sickle cell disease that was funded and regulated by the FDA. CONCLUSION: The goal of DSMPs regardless of the phase of the clinical trial is to protect participant safety and ensure the integrity and validity of the data. A DSMB can ensure that risks and data are evaluated in a timely, efficient, and unbiased manner. We describe "risk-based" guidelines to determine situations in which a DSMB may be an appropriate addition to a DSMP for phase I and II clinical trials. We also address the roles and responsibilities of the DSMB for these studies.

Relationship of pulmonary artery catheter use to mortality and resource utilization in patients with severe sepsis.

OBJECTIVE: To examine the relationship of pulmonary artery catheter (PAC) use to patient outcomes, including mortality rate and resource utilization, in patients with severe sepsis in eight academic medical centers. DESIGN: Case-control, nested within a prospective cohort study. SETTING: Eight academic tertiary care centers. PATIENTS: Stratified random sample of 1,010 adult admissions with severe sepsis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The main outcome measures were in-hospital mortality, total hospital charge, and length of stay (LOS) for patients with and without PAC use. The case-matched subset of patients included 141 pairs managed with and without the use of a PAC. The mortality rate was slightly but not statistically significantly lower among the PAC use group compared with those not using a PAC (41.1% vs. 46.8%, p =.34). Even this trend disappeared after we adjusted for the Charlson comorbidity score and sepsis-specific Acute Physiology and Chronic Health Evaluation (APACHE) III (adjusted odds ratio, 1.02; 95% confidence interval, 0.61-1.72). In linear regression models adjusted for the Charlson comorbidity score, sepsis-specific APACHE III, surgical status, receipt of a steroid before sepsis onset, presence of a Hickman catheter, and preonset LOS, no significant differences were found for total hospital charges (139,207 US dollars vs. 148,190, adjusted mean comparing PAC and non-PAC group, p =.57), postonset LOS (23.4 vs. 26.9 days, adjusted mean, p =.32), or total LOS in intensive care unit (18.2 vs. 18.8 days, adjusted mean, p =.82). CONCLUSIONS: Among patients with severe sepsis, PAC placement was not associated with a change in mortality rate or resource utilization, although small nonsignificant trends toward lower resource utilization were present in the PAC group.

Severe sepsis: variation in resource and therapeutic modality use among academic centers.

BACKGROUND: Treatment of severe sepsis is expensive, often encompassing a number of discretionary modalities. The objective of the present study was to assess intercenter variation in resource and therapeutic modality use in patients with severe sepsis. METHODS: We conducted a prospective cohort study of 1028 adult admissions with severe sepsis from a stratified random sample of patients admitted to eight academic tertiary care centers. The main outcome measures were length of stay (LOS; total LOS and LOS after onset of severe sepsis) and total hospital charges. RESULTS: The adjusted mean total hospital charges varied from 69 429 dollars to US237 898 dollars across centers, whereas the adjusted LOS after onset varied from 15.9 days to 24.2 days per admission. Treatments used frequently after the first onset of sepsis among patients with severe sepsis were pulmonary artery catheters (19.4%), ventilator support (21.8%), pressor support (45.8%) and albumin infusion (14.4%). Pulmonary artery catheter use, ventilator support and albumin infusion had moderate variation profiles, varying 3.2-fold to 4.9-fold, whereas the rate of pressor support varied only 1.92-fold across centers. Even after adjusting for age, sex, Charlson comorbidity score, discharge diagnosis-relative group weight, organ dysfunction and service at onset, the odds for using these therapeutic modalities still varied significantly across centers. Failure to start antibiotics within 24 hours was strongly correlated with a higher probability of 28-day mortality (r2 = 0.72). CONCLUSION: These data demonstrate moderate but significant variation in resource use and use of technologies in treatment of severe sepsis among academic centers. Delay in antibiotic therapy was associated with worse outcome at the center level.

Preliminary assessment of inhaled nitric oxide for acute vaso-occlusive crisis in pediatric patients with sickle cell disease.

CONTEXT: Vaso-occlusion is central to the painful crises and acute and chronic organ damage in sickle cell disease. Abnormal nitric oxide-dependent regulation of vascular tone, adhesion, platelet activation, and inflammation contributes to the pathophysiology of vaso-occlusion. Nitric oxide may have promise as a mechanism-of-disease-based therapy for treatment of vaso-occlusion. OBJECTIVE: To explore the efficacy and safety of inhaled nitric oxide (INO) for treatment of vaso-occlusive crisis in pediatric patients. DESIGN: Prospective, double-blind, placebo-controlled, randomized clinical trial with enrollment between September 1999 and October 2001. SETTING: Urban, tertiary care children's hospital in the United States. PARTICIPANTS: Twenty patients aged 10 to 21 years with sickle cell disease and severe acute vaso-occlusive crisis. INTERVENTION: Patients were randomly assigned to receive INO (80 ppm with 21% final concentration of inspired oxygen; n = 10), or placebo (21% inspired oxygen; n = 10) for 4 hours. MAIN OUTCOME MEASURES: Change in pain at 4 hours of inhalation compared with preinhalation pain, measured on a 10-cm visual analog scale (VAS); secondary outcome measures were pain over 6 hours, parenteral narcotic use over 24 hours, duration of hospitalization, blood pressure, oxygen saturation, and methemoglobin concentration. RESULTS: Preinhalation VAS pain scores were similar in the INO and placebo groups (P =.80). The decrease in VAS pain scores at 4 hours was 2.0 cm in the INO group and 1.2 cm in the placebo group (P =.37). Repeated-measures analysis of variance for hourly pain scores showed a 1-cm/h greater reduction in the INO group than the placebo group (P =.02). Morphine use over 6 hours was significantly less in the INO group (mean cumulative use, 0.29 vs 0.44 mg/kg; P =.03) but was not different over 4 hours (0.26 vs 0.32 mg/kg; P =.21) or 24 hours (0.63 vs 0.91 mg/kg; P =.15). Duration of hospitalization was 78 and 100 hours in the INO and placebo groups, respectively (P =.19). No INO toxicity was observed. CONCLUSIONS: Results of this exploratory study suggest that INO may be beneficial for acute vaso-occlusive crisis. These preliminary results warrant further investigation.

Resource utilization among patients with sepsis syndrome.

OBJECTIVE: To assess the resource utilization associated with sepsis syndrome in academic medical centers. DESIGN: Prospective cohort study. SETTING: Eight academic, tertiary-care centers. PATIENTS: Stratified random sample of 1,028 adult admissions with sepsis syndrome and all 248,761 other adult admissions between January 1993 and April 1994. The main outcome measures were length of stay (LOS) in total and after onset of sepsis syndrome (post-onset LOS) and total hospital charges. RESULTS: The mean LOS for patients with sepsis was 27.7 +/- 0.9 days (median, 20 days), with sepsis onset occurring after a mean of 8.1 +/- 0.4 days (median, 3 days). For all patients without sepsis, the LOS was 7.2 +/- 0.03 days (median, 4 days). In multiple linear regression models, the mean for patients with sepsis syndrome was 18.2 days, which was 11.0 days longer than the mean for all other patients (P < .0001), whereas the mean difference in total charges was $43,000 (both P < .0001). These differences were greater for patients with nosocomial as compared with community-acquired sepsis, although the groups were similar after adjusting for pre-onset LOS. Eight independent correlates of increased post-onset LOS and 12 correlates of total charges were identified. CONCLUSIONS: These data quantify the resource utilization associated with sepsis syndrome, and demonstrate that resource utilization is high in this group. Additional investigation is required to determine how much of the excess post-onset LOS and charges are attributable to sepsis syndrome rather than the underlying medical conditions.