Severe Maternal Morbidity from Pregnancy through 1-year Postpartum.

BACKGROUND: Few recent studies have examined the rate of severe maternal morbidity (SMM) occurring during the antenatal and/or the postpartum period through 42 days postpartum. However, little is known about the rate of SMM occurring beyond 42 days postpartum. OBJECTIVE: To examine the distribution of SMM and its indicators during antenatal, delivery, and postpartum hospitalizations through 365 days postpartum, and to estimate the increase in SMM rate and its indicators after accounting for antenatal and postpartum SMM through 365 days postpartum. STUDY DESIGN: We conducted a retrospective cohort study using birth and fetal death certificate data linked to hospital discharge records from Michigan, Oregon, and South Carolina from 2008-2020. We examined the distribution of SMM, non-transfusion SMM, and SMM indicators during antenatal, delivery, and postpartum hospitalizations through 365 days postpartum. We subsequently examined "SMM cases added," which represent cases among unique individuals that are included by considering the antenatal and postpartum periods but that would be missed if only the delivery hospitalization cases were included. RESULTS: A total of 64,661 (2.5%) individuals experienced SMM while 37,112 (1.4%) individuals experienced non-transfusion SMM during antenatal, delivery, and/or postpartum hospitalization. A total of 31% of SMM cases were added after accounting for SMM occurring during the antenatal or postpartum hospitalization through 365 days postpartum while 49% of non-transfusion SMM cases were added after accounting for non-transfusion SMM occurring during the antenatal or postpartum periods. SMM occurring between 43 and 365 days postpartum contributed to 12% of all SMM cases while non-transfusion SMM occurring between 43 and 365 days postpartum contributed to 19% of all non-transfusion SMM cases. CONCLUSION: We showed that a total of 31% of SMM and 49% of non-transfusion SMM cases were added after accounting for SMM occurring during the antenatal or postpartum hospitalization through 365 days postpartum. Our findings highlight the importance of expanding the SMM definition beyond the delivery hospitalization to better capture the full period of increased risk, identify contributing factors, and design strategies to mitigate this risk. Only then, can we improve outcomes for mothers and subsequently the quality of life of their infants.

Association between stillbirth and severe maternal morbidity.

BACKGROUND: Severe maternal morbidity has been increasing in the past few decades. Few studies have examined the risk of severe maternal morbidity among individuals with stillbirths vs individuals with live-birth deliveries. OBJECTIVE: This study aimed to examine the prevalence and risk of severe maternal morbidity among individuals with stillbirths vs individuals with live-birth deliveries during delivery hospitalization as a primary outcome and during the postpartum period as a secondary outcome. STUDY DESIGN: This was a retrospective cohort study using birth and fetal death certificate data linked to hospital discharge records from California (2008-2018), Michigan (2008-2020), Missouri (2008-2014), Pennsylvania (2008-2014), and South Carolina (2008-2020). Relative risk regression analysis was used to examine the crude and adjusted relative risks of severe maternal morbidity along with 95% confidence intervals among individuals with stillbirths vs individuals with live-birth deliveries, adjusting for birth year, state of residence, maternal sociodemographic characteristics, and the obstetric comorbidity index. RESULTS: Of the 8,694,912 deliveries, 35,012 (0.40%) were stillbirths. Compared with individuals with live-birth deliveries, those with stillbirths were more likely to be non-Hispanic Black (10.8% vs 20.5%); have Medicaid (46.5% vs 52.0%); have pregnancy complications, including preexisting diabetes mellitus (1.1% vs 4.3%), preexisting hypertension (2.3% vs 6.2%), and preeclampsia (4.4% vs 8.4%); have multiple pregnancies (1.6% vs 6.2%); and reside in South Carolina (7.4% vs 11.6%). During delivery hospitalization, the prevalence rates of severe maternal morbidity were 791 cases per 10,000 deliveries for stillbirths and 154 cases per 10,000 deliveries for live-birth deliveries, whereas the prevalence rates for nontransfusion severe maternal morbidity were 502 cases per 10,000 deliveries for stillbirths and 68 cases per 10,000 deliveries for live-birth deliveries. The crude relative risk for severe maternal morbidity was 5.1 (95% confidence interval, 4.9-5.3), whereas the adjusted relative risk was 1.6 (95% confidence interval, 1.5-1.8). For nontransfusion severe maternal morbidity among stillbirths vs live-birth deliveries, the crude relative risk was 7.4 (95% confidence interval, 7.0-7.7), whereas the adjusted relative risk was 2.0 (95% confidence interval, 1.8-2.3). This risk was not only elevated among individuals with stillbirth during the delivery hospitalization but also through 1 year after delivery (severe maternal morbidity adjusted relative risk, 1.3; 95% confidence interval, 1.1-1.4; nontransfusion severe maternal morbidity adjusted relative risk, 1.2; 95% confidence interval, 1.1-1.3). CONCLUSION: Stillbirth was found to be an important contributor to severe maternal morbidity.

Trends in Mortality and Morbidities for Infants Born 24 to 28 Weeks in the US: 1997-2021.

BACKGROUND: Mortality and morbidity for very preterm infants in the United States decreased for years. The current study describes recent changes to assess whether the pace of improvement has changed. METHODS: Vermont Oxford Network members contributed data on infants born at 24 to 28 weeks' gestation from 1997 to 2021. We modeled mortality, late-onset sepsis, necrotizing enterocolitis, chronic lung disease, severe intraventricular hemorrhage, severe retinopathy of prematurity, and death or morbidity by year of birth using segmented relative risk regression, reporting risk-adjusted annual percentage changes with 95% confidence intervals overall and by gestational age week. RESULTS: Analyses of data for 447 396 infants at 888 hospitals identified 3 time point segments for mortality, late onset sepsis, chronic lung disease, severe intraventricular hemorrhage, severe retinopathy of prematurity, and death or morbidity, and 4 for necrotizing enterocolitis. Mortality decreased from 2005 to 2021, but more slowly since 2012. Late-onset sepsis decreased from 1997 to 2021, but more slowly since 2012. Severe retinopathy of prematurity decreased from 2002 to 2021, but more slowly since 2011. Necrotizing enterocolitis, severe intraventricular hemorrhage, and death or morbidity were stable since 2015. Chronic lung disease has increased since 2012. Trends by gestational age generally mirror those for the overall cohort. CONCLUSIONS: Improvements in mortality and morbidity have slowed, stalled, or reversed in recent years. We propose a 3-part strategy to regain the pace of improvement: research; quality improvement; and follow through, practicing social as well as technical medicine to improve the health and well-being of infants and families.

Association of Sickle Cell Disease With Racial Disparities and Severe Maternal Morbidities in Black Individuals.

Importance: Little is known about the association between sickle cell disease (SCD) and severe maternal morbidity (SMM). Objective: To examine the association of SCD with racial disparities in SMM and with SMM among Black individuals. Design, Setting, and Participants: This cohort study was a retrospective population-based investigation of individuals with and without SCD in 5 states (California [2008-2018], Michigan [2008-2020], Missouri [2008-2014], Pennsylvania [2008-2014], and South Carolina [2008-2020]) delivering a fetal death or live birth. Data were analyzed between July and December 2022. Exposure: Sickle cell disease identified during the delivery admission by using International Classification of Diseases, Ninth Revision and Tenth Revision codes. Main Outcomes and Measures: The primary outcomes were SMM including and excluding blood transfusions during the delivery hospitalization. Modified Poisson regression was used to estimate risk ratios (RRs) adjusted for birth year, state, insurance type, education, maternal age, Adequacy of Prenatal Care Utilization Index, and obstetric comorbidity index. Results: From a sample of 8 693 616 patients (mean [SD] age, 28.5 [6.1] years), 956 951 were Black individuals (11.0%), of whom 3586 (0.37%) had SCD. Black individuals with SCD vs Black individuals without SCD were more likely to have Medicaid insurance (70.2% vs 64.6%), to have a cesarean delivery (44.6% vs 34.0%), and to reside in South Carolina (25.2% vs 21.5%). Sickle cell disease accounted for 8.9% and for 14.3% of the Black-White disparity in SMM and nontransfusion SMM, respectively. Among Black individuals, SCD complicated 0.37% of the pregnancies but contributed to 4.3% of the SMM cases and to 6.9% of the nontransfusion SMM cases. Among Black individuals with SCD compared with those without, the crude RRs of SMM and nontransfusion SMM during the delivery hospitalization were 11.9 (95% CI, 11.3-12.5) and 19.8 (95% CI, 18.5-21.2), respectively, while the adjusted RRs were 3.8 (95% CI, 3.3-4.5) and 6.5 (95% CI, 5.3-8.0), respectively. The SMM indicators that incurred the highest adjusted RRs included air and thrombotic embolism (4.8; 95% CI, 2.9-7.8), puerperal cerebrovascular disorders (4.7; 95% CI, 3.0-7.4), and blood transfusion (3.7; 95% CI, 3.2-4.3). Conclusions and Relevance: In this retrospective cohort study, SCD was found to be an important contributor to racial disparities in SMM and was associated with an elevated risk of SMM among Black individuals. Efforts from the research community, policy makers, and funding agencies are needed to advance care among individuals with SCD.

Assessment of an Updated Neonatal Research Network Extremely Preterm Birth Outcome Model in the Vermont Oxford Network.

Importance: The Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (NRN) extremely preterm birth outcome model is widely used for prognostication by practitioners caring for families expecting extremely preterm birth. The model provides information on mean outcomes from 1998 to 2003 and does not account for substantial variation in outcomes among US hospitals. Objective: To update and validate the NRN extremely preterm birth outcome model for most extremely preterm infants in the United States. Design, Setting, and Participants: This prognostic study included 3 observational cohorts from January 1, 2006, to December 31, 2016, at 19 US centers in the NRN (derivation cohort) and 637 US centers in Vermont Oxford Network (VON) (validation cohorts). Actively treated infants born at 22 weeks' 0 days' to 25 weeks' 6 days' gestation and weighing 401 to 1000 g, including 4176 in the NRN for 2006 to 2012, 45 179 in VON for 2006 to 2012, and 25 969 in VON for 2013 to 2016, were studied. VON cohorts comprised more than 85% of eligible US births. Data analysis was performed from May 1, 2017, to March 31, 2019. Exposures: Predictive variables used in the original model, including infant sex, birth weight, plurality, gestational age at birth, and exposure to antenatal corticosteroids. Main Outcomes and Measures: The main outcome was death before discharge. Secondary outcomes included neurodevelopmental impairment at 18 to 26 months' corrected age and measures of hospital resource use (days of hospitalization and ventilator use). Results: Among 4176 actively treated infants in the NRN cohort (48% female; mean [SD] gestational age, 24.2 [0.8] weeks), survival was 63% vs 62% among 3702 infants in the era of the original model (47% female; mean [SD] gestational age, 24.2 [0.8] weeks). In the concurrent (2006-2012) VON cohort, survival was 66% among 45 179 actively treated infants (47% female; mean [SD] gestational age, 24.1 [0.8] weeks) and 70% among 25 969 infants from 2013 to 2016 (48% female; mean [SD] gestational age, 24.1 [0.8] weeks). Model C statistics were 0.74 in the 2006-2012 validation cohort and 0.73 in the 2013-2016 validation cohort. With the use of decision curve analysis to compare the model with a gestational age-only approach to prognostication, the updated model showed a predictive advantage. The birth hospital contributed equally as much to prediction of survival as gestational age (20%) but less than the other factors combined (60%). Conclusions and Relevance: An updated model using well-known factors to predict survival for extremely preterm infants performed moderately well when applied to large US cohorts. Because survival rates change over time, the model requires periodic updating. The hospital of birth contributed substantially to outcome prediction.

A Tandem Evolutionary Algorithm for Identifying Causal Rules from Complex Data.

We propose a new evolutionary approach for discovering causal rules in complex classification problems from batch data. Key aspects include (a) the use of a hypergeometric probability mass function as a principled statistic for assessing fitness that quantifies the probability that the observed association between a given clause and target class is due to chance, taking into account the size of the dataset, the amount of missing data, and the distribution of outcome categories, (b) tandem age-layered evolutionary algorithms for evolving parsimonious archives of conjunctive clauses, and disjunctions of these conjunctions, each of which have probabilistically significant associations with outcome classes, and (c) separate archive bins for clauses of different orders, with dynamically adjusted order-specific thresholds. The method is validated on majority-on and multiplexer benchmark problems exhibiting various combinations of heterogeneity, epistasis, overlap, noise in class associations, missing data, extraneous features, and imbalanced classes. We also validate on a more realistic synthetic genome dataset with heterogeneity, epistasis, extraneous features, and noise. In all synthetic epistatic benchmarks, we consistently recover the true causal rule sets used to generate the data. Finally, we discuss an application to a complex real-world survey dataset designed to inform possible ecohealth interventions for Chagas disease.

A trauma mortality prediction model based on the ICD-10-CM lexicon: TMPM-ICD10.

BACKGROUND: Outcome prediction models allow risk adjustment required for trauma research and the evaluation of outcomes. The advent of ICD-10-CM has rendered risk adjustment based on ICD-9-CM codes moot, but as yet no risk adjustment model based on ICD-10-CM codes has been described. METHODS: The National Trauma Data Bank provided data from 773,388 injured patients who presented to one of 747 trauma centers in 2016 with traumatic injuries ICD-10-CM codes and Injury Severity Score (ISS). We constructed an outcome prediction model using only ICD-10-CM acute injury codes and compared its performance with that of the ISS. RESULTS: Compared with ISS, the TMPM-ICD-10 discriminated survivors from non-survivors better (ROC TMPM-ICD-10 = 0.861 [0.860-0.872], ROC [reviever operating curve] ISS = 0.830 [0.823-0.836]), was better calibrated (HL [Hosmer-Lemeshow statistic] TMPM-ICD-10 = 49.01, HL ISS = 788.79), and had a lower Akaike information criteria (AIC TMPM-ICD10 = 30579.49; AIC ISS = 31802.18). CONCLUSIONS: Because TMPM-ICD10 provides better discrimination and calibration than the ISS and can be computed without recourse to Abbreviated Injury Scale coding, the TMPM-ICD10 should replace the ISS as the standard measure of overall injury severity for data coded in the ICD-10-CM lexicon. LEVEL OF EVIDENCE: Prognostic/Epidemiologic, level II.

Variation in readmission rates among hospitals following admission for traumatic injury.

INTRODUCTION: Readmission following hospital discharge is both common and costly. The Hospital Readmission Reduction Program (HRRP) financially penalizes hospitals for readmission following admission for some conditions, but this approach may not be appropriate for all conditions. We wished to determine if hospitals differed in their adjusted readmission rates following an index hospital admission for traumatic injury. PATIENTS AND METHODS: We extracted from the AHRQ National Readmission Dataset (NRD) all non-elderly adult patients hospitalized following traumatic injury in 2014. We estimated hierarchal logistic regression models to predicted readmission within 30 days. Models included either patient level predictors, hospital level predictors, or both. We quantified the extent of hospital variability in readmissions using the median odds ratio. Additionally, we computed hospital specific risk-adjusted rates of readmission and number of excess readmissions. RESULTS: Of the 177,322 patients admitted for traumatic injury 11,940 (6.7%) were readmitted within 30 days. Unadjusted hospital readmission rates for the 637 hospitals in our study varied from 0% to 20%. After controlling for sources of variability the range for hospital readmission rates was between 5.5% and 8.5%. Only 2% of hospitals had a random intercept coefficient significantly different from zero, suggesting that their readmission rates differed from the mean level of all hospitals. We also estimated that in 2014 only 11% of hospitals had more than 2 excess readmissions. Our multilevel model discriminated patients who were readmitted from those not readmitted at an acceptable level (C = 0.74). CONCLUSIONS: We found little evidence that hospitals differ in their readmission rates following an index admission for traumatic injury. There is little justification for penalizing hospitals based on readmissions after traumatic injury.

Association of Antenatal Steroid Exposure With Survival Among Infants Receiving Postnatal Life Support at 22 to 25 Weeks' Gestation.

Importance: Although evidence of antenatal steroids (ANS) efficacy at 22 to 25 weeks' gestation is limited, increasingly these infants are treated with postnatal life support. Objectives: To estimate the proportion of infants receiving postnatal life support at 22 to 25 weeks' gestation who had exposure to ANS, and to examine if the provision of ANS was associated with a higher rate of survival to hospital discharge and survival without major morbidities. Design, Setting, and Participants: This multicenter observational cohort study consisted of 33 472 eligible infants liveborn at 431 US Vermont Oxford Network member hospitals between January 1, 2012, and December 31, 2016. We excluded infants with recognized syndromes or major congenital anomalies. Of the eligible infants, 29 932 received postnatal life support and were included in the analyses. Data analysis was conducted from July 2017 to July 2018. Exposure: Antenatal steroids administered to the mother at any time prior to delivery. Main Outcomes and Measures: Survival to hospital discharge, major morbidities among survivors, and the composite of survival to discharge without major morbidities. Results: Among 29 932 infants who received postnatal life support, 51.9% were male, with a mean (SD) gestational age of 24.12 (0.86) weeks and mean (SD) birth weight of 668 (140) g; 26 090 (87.2%) had ANS exposure and 3842 (12.8%) had no ANS exposure. Survival to hospital discharge was higher for infants with ANS exposure (18 717 of 25 892 [72.3%]) compared with infants without ANS exposure (1981 of 3820 [51.9%]); the adjusted risk ratio for 22 weeks was 2.11 (95% CI, 1.68-2.65), for 23 weeks was 1.54 (95% CI, 1.40-1.70), for 24 weeks was 1.18 (95% CI, 1.12-1.25), and for 25 weeks was 1.11 (95% CI, 1.07-1.14). Survival to hospital discharge without major morbidities was higher for infants with ANS exposure (3777 of 25 833 [14.6%]) compared with infants without ANS exposure (347 of 3806 [9.1%]); the adjusted risk ratio for 22 through 25 weeks was 1.67 (95% CI, 1.49-1.87). Conclusions and Relevance: Concordant receipt of ANS and postnatal life support was associated with significantly higher survival and survival without major morbidities at 22 through 25 weeks' gestation compared with life support alone. Although statistically higher with ANS, survival without major morbidities remains low at 22 and 23 weeks. There is an opportunity to reevaluate national obstetric guidelines, allowing for shared decision making at the edge of viability with concordant obstetrical and neonatal treatment plans.

Variation in Performance of Neonatal Intensive Care Units in the United States.

Importance: Hospitals use rates from the best quartile or decile as benchmarks for quality improvement aims, but to what extent these aims are achievable is uncertain. Objective: To determine the proportion of neonatal intensive care units (NICUs) in 2014 that achieved rates for death and major morbidities as low as the shrunken adjusted rates from the best quartile and decile in 2005 and the time it took to achieve those rates. Design, Setting, and Participants: A total of 408 164 infants with a birth weight of 501 to 1500 g born from January 1, 2005, to December 31, 2014, and cared for at 756 Vermont Oxford Network member NICUs in the United States were evaluated. Logistic regression models with empirical Bayes factors were used to estimate standardized morbidity ratios for each NICU. Each ratio was multiplied by the overall network rate to calculate the 10th, 25th, 50th, 75th, and 90th percentiles of the shrunken adjusted rates for each year. The proportion in 2014 that achieved the 10th and 25th percentile rates from 2005 and the number of years it took for 75% of NICUs to achieve the 2005 rates from the best quartile were estimated. Main Outcomes and Measures: Death prior to hospital discharge, infection more than 3 days after birth, severe retinopathy of prematurity, severe intraventricular hemorrhage, necrotizing enterocolitis, and chronic lung disease among infants less than 33 weeks' gestational age at birth. Results: Of the 756 hospitals, 695 provided data for 2014. The mean unadjusted infant-level rate of death before hospital discharge decreased from 14.0% in 2005 to 10.9% in 2014. In 2014, 689 of 695 NICUs (99.1%; 95% CI, 97.4%-100.0%) achieved the 2005 shrunken adjusted rates from the best quartile for death prior to discharge, 678 of 695 (97.6%; 95% CI, 95.8%-99.6%) for late-onset infection, 558 of 681 (81.9%; 95% CI, 77.2%-86.6%) for severe retinopathy of prematurity, 611 of 693 (88.2%; 95% CI, 81.7%-97.0%) for severe intraventricular hemorrhage, 529 of 696 (76.0%; 95% CI, 71.8%-81.2%) for necrotizing enterocolitis, and 286 of 693 (41.3%; 95% CI, 36.1%-45.6%) for chronic lung disease. It took 3 years before 445 NICUs (75.0%) achieved the 2005 shrunken adjusted rate from the best quartile for death prior to discharge, 5 years to achieve the rate from the best quartile for late-onset infection, 6 years to achieve the rate from the best quartile for severe retinopathy of prematurity and severe intraventricular hemorrhage, and 8 years to achieve the rate from the best quartile for necrotizing enterocolitis. Conclusions and Relevance: From 2005 to 2014, rates of death prior to discharge and serious morbidities decreased among the NICUs in this study. Within 8 years, 75% of NICUs achieved rates of performance from the best quartile of the 2005 benchmark for all outcomes except chronic lung disease. These findings provide a novel way to quantify the magnitude and pace of improvement in neonatology.

Tunably Rugged Landscapes With Known Maximum and Minimum.

We propose NM landscapes as a new class of tunably rugged benchmark problems. NM landscapes are well defined on alphabets of any arity, including both discrete and real-valued alphabets, include epistasis in a natural and transparent manner, are proven to have known value and location of the global maximum and, with some additional constraints, are proven to also have a known global minimum. Empirical studies are used to illustrate that, when coefficients are selected from a recommended distribution, the ruggedness of NM landscapes is smoothly tunable and correlates with several measures of search difficulty. We discuss why these properties make NM landscapes preferable to both NK landscapes and Walsh polynomials as benchmark landscape models with tunable epistasis.

Weight Growth Velocity and Postnatal Growth Failure in Infants 501 to 1500 Grams: 2000-2013.

BACKGROUND: Very low birth weight infants often gain weight poorly and demonstrate growth failure during the initial hospitalization. Although many of the major morbidities experienced by these infants during their initial NICU stays have decreased in recent years, it is unclear whether growth has improved. METHODS: We studied 362 833 infants weighing 501 to 1500 g without major birth defects born from 2000 to 2013 and who were hospitalized for 15 to 175 days at 736 North American hospitals in the Vermont Oxford Network. Average growth velocity (GV; g/kg per day) was computed by using a 2-point exponential model on the basis of birth weight and discharge weight. Postnatal growth failure and severe postnatal growth failure were defined as a discharge weight less than the 10th and third percentiles for postmenstrual age, respectively. RESULTS: From 2000 to 2013, average GV increased from 11.8 to 12.9 g/kg per day. Postnatal growth failure decreased from 64.5% to 50.3% and severe postnatal growth failure from 39.8% to 27.5%. The interquartile ranges for the hospitals participating in 2013 were as follows: GV, 12.3 to 13.4 g/kg per day; postnatal growth failure, 41.1% to 61.7%; and severe postnatal growth failure, 19.4% to 36.0%. Adjusted and unadjusted estimates were nearly identical. CONCLUSIONS: For infants weighing 501 to 1500 g at birth, average GV increased and the percentage with postnatal growth failure decreased. However, in 2013, half of these infants still demonstrated postnatal growth failure and one-quarter demonstrated severe postnatal growth failure.

Obstetric and neonatal care practices for infants 501 to 1500 g from 2000 to 2009.

OBJECTIVE: To identify changes in clinical practices for infants with birth weights of 501 to 1500 g born from 2000 to 2009. METHODS: We used prospectively collected registry data for 355,806 infants born from 2000 to 2009 and cared for at 669 North American hospitals in the Vermont Oxford Network. Main outcome measures included obstetric and neonatal practices, including cesarean delivery, antenatal steroids, delivery room interventions, respiratory practices, neuroimaging, retinal exams, and feeding at discharge. RESULTS: Significant changes in many obstetric, delivery room, and neonatal practices occurred from 2000 to 2009. Use of surfactant treatment in the delivery room increased overall (adjusted difference [AD] 17.0%; 95% confidence interval [CI] 16.4% to 17.6%), as did less-invasive methods of respiratory support, such as nasal continuous positive airway pressure (AD 9.9%; 95% CI 9.1% to 10.6%). Use of any ventilation (AD -7.5%; 95% CI -8.0% to -6.9%) and steroids for chronic lung disease (AD -15.3%; 95% CI -15.8% to -14.8%) decreased significantly overall. Most of the changes in respiratory care were observed within each of 4 birth weight strata (501-750 g, 751-1000 g, 1001-1250 g, 1251-1500 g). CONCLUSIONS: Many obstetric and neonatal care practices used in the management of infants 501 to 1500 g changed between 2000 and 2009. In particular, less-invasive approaches to respiratory support increased.

Searching the clinical fitness landscape.

Widespread unexplained variations in clinical practices and patient outcomes suggest major opportunities for improving the quality and safety of medical care. However, there is little consensus regarding how to best identify and disseminate healthcare improvements and a dearth of theory to guide the debate. Many consider multicenter randomized controlled trials to be the gold standard of evidence-based medicine, although results are often inconclusive or may not be generally applicable due to differences in the contexts within which care is provided. Increasingly, others advocate the use "quality improvement collaboratives", in which multi-institutional teams share information to identify potentially better practices that are subsequently evaluated in the local contexts of specific institutions, but there is concern that such collaborative learning approaches lack the statistical rigor of randomized trials. Using an agent-based model, we show how and why a collaborative learning approach almost invariably leads to greater improvements in expected patient outcomes than more traditional approaches in searching simulated clinical fitness landscapes. This is due to a combination of greater statistical power and more context-dependent evaluation of treatments, especially in complex terrains where some combinations of practices may interact in affecting outcomes. The results of our simulations are consistent with observed limitations of randomized controlled trials and provide important insights into probable reasons for effectiveness of quality improvement collaboratives in the complex socio-technical environments of healthcare institutions. Our approach illustrates how modeling the evolution of medical practice as search on a clinical fitness landscape can aid in identifying and understanding strategies for improving the quality and safety of medical care.

Mortality and neonatal morbidity among infants 501 to 1500 grams from 2000 to 2009.

OBJECTIVE: To identify changes in mortality and neonatal morbidities for infants with birth weight 501 to 1500 g born from 2000 to 2009. METHODS: There were 355806 infants weighing 501 to 1500 g who were born in 2000-2009. Mortality during initial hospitalization and major neonatal morbidity in survivors (early and late infection, chronic lung disease, necrotizing enterocolitis, severe retinopathy of prematurity, severe intraventricular hemorrhage, and periventricular leukomalacia) were assessed by using data from 669 North American hospitals in the Vermont Oxford Network. RESULTS: From 2000 to 2009, mortality for infants weighing 501 to 1500 g decreased from 14.3% to 12.4% (difference, -1.9%; 95% confidence interval, -2.3% to -1.5%). Major morbidity in survivors decreased from 46.4% to 41.4% (difference, -4.9%; 95% confidence interval, -5.6% to -4.2%). In 2009, mortality ranged from 36.6% for infants 501 to 750 g to 3.5% for infants 1251 to 1500 g, whereas major morbidity in survivors ranged from 82.7% to 18.7%. In 2009, 49.2% of all very low birth weight infants and 89.2% of infants 501 to 750 g either died or survived with a major neonatal morbidity. CONCLUSIONS: Mortality and major neonatal morbidity in survivors decreased for infants with birth weight 501 to 1500 g between 2000 and 2009. However, at the end of the decade, a high proportion of these infants still either died or survived after experiencing ≥ 1 major neonatal morbidity known to be associated with both short- and long-term adverse consequences.

Electrogram fractionation: the relationship between spatiotemporal variation of tissue excitation and electrode spatial resolution.

BACKGROUND: Fractionated electrograms are used by some as targets for ablation in atrial and ventricular arrhythmias. Fractionation has been demonstrated to result when there is repetitive or asynchronous activation of separate groups of cells within the recording region of a mapping electrode(s). METHODS AND RESULTS: Using a computer model, we generated tissue activation patterns with increasing spatiotemporal variation and calculated virtual electrograms from electrodes with decreasing resolution. We then quantified electrogram fractionation. In addition, we recorded unipolar electrograms during atrial fibrillation in 20 patients undergoing atrial fibrillation ablation. From these we constructed bipolar electrograms with increasing interelectrode spacing and quantified fractionation. During modeling of spatiotemporal variation, fractionation varied directly with electrode length, diameter, height, and interelectrode spacing. When resolution was held constant, fractionation increased with increasing spatiotemporal variation. In the absence of spatial variation, fractionation was independent of resolution and proportional to excitation frequency. In patients with atrial fibrillation, fractionation increased as interelectrode spacing increased. CONCLUSIONS: We created a model for distinguishing the roles of spatial and temporal electric variation and electrode resolution in producing electrogram fractionation. Spatial resolution affects fractionation attributable to spatiotemporal variation but not temporal variation alone. Electrogram fractionation was directly proportional to spatiotemporal variation and inversely proportional to spatial resolution. Spatial resolution limits the ability to distinguish high-frequency excitation from overcounting. In patients with atrial fibrillation, complex fractionated atrial electrogram detection varies with spatial resolution. Electrode resolution must therefore be considered when interpreting and comparing studies of fractionation.

Split-plot designs for robotic serial dilution assays.

This article explores effective implementation of split-plot designs in serial dilution bioassay using robots. We show that the shortest path for a robot to fill plate wells for a split-plot design is equivalent to the shortest common supersequence problem in combinatorics. We develop an algorithm for finding the shortest common supersequence, provide an R implementation, and explore the distribution of the number of steps required to implement split-plot designs for bioassay through simulation. We also show how to construct collections of split plots that can be filled in a minimal number of steps, thereby demonstrating that split-plot designs can be implemented with nearly the same effort as strip-plot designs. Finally, we provide guidelines for modeling data that result from these designs.

Power and sample size calculations for generalized regression models with covariate measurement error.

Covariate measurement error is often a feature of scientific data used for regression modelling. The consequences of such errors include a loss of power of tests of significance for the regression parameters corresponding to the true covariates. Power and sample size calculations that ignore covariate measurement error tend to overestimate power and underestimate the actual sample size required to achieve a desired power. In this paper we derive a novel measurement error corrected power function for generalized linear models using a generalized score test based on quasi-likelihood methods. Our power function is flexible in that it is adaptable to designs with a discrete or continuous scalar covariate (exposure) that can be measured with or without error, allows for additional confounding variables and applies to a broad class of generalized regression and measurement error models. A program is described that provides sample size or power for a continuous exposure with a normal measurement error model and a single normal confounder variable in logistic regression. We demonstrate the improved properties of our power calculations with simulations and numerical studies. An example is given from an ongoing study of cancer and exposure to arsenic as measured by toenail concentrations and tap water samples.