Association of common maternal infections with birth outcomes: a multinational cohort study.

PURPOSE: It is unclear whether common maternal infections during pregnancy are risk factors for adverse birth outcomes. We assessed the association between self-reported infections during pregnancy with preterm birth and small-for-gestational-age (SGA) in an international cohort consortium. METHODS: Data on 120,507 pregnant women were obtained from six population-based birth cohorts in Australia, Denmark, Israel, Norway, the UK and the USA. Self-reported common infections during pregnancy included influenza-like illness, common cold, any respiratory tract infection, vaginal thrush, vaginal infections, cystitis, urinary tract infection, and the symptoms fever and diarrhoea. Birth outcomes included preterm birth, low birth weight and SGA. Associations between maternal infections and birth outcomes were first assessed using Poisson regression in each cohort and then pooled using random-effect meta-analysis. Risk ratios (RR) and 95% confidence intervals (CI) were calculated, adjusted for potential confounders. RESULTS: Vaginal infections (pooled RR, 1.10; 95% CI, 1.02-1.20) and urinary tract infections (pooled RR, 1.17; 95% CI, 1.09-1.26) during pregnancy were associated with higher risk of preterm birth. Similar associations with low birth weight were also observed for these two infections. Fever during pregnancy was associated with higher risk of SGA (pooled RR, 1.07; 95% CI, 1.02-1.12). No other significant associations were observed between maternal infections/symptoms and birth outcomes. CONCLUSION: Vaginal infections and urinary infections during pregnancy were associated with a small increased risk of preterm birth and low birth weight, whereas fever was associated with SGA. These findings require confirmation in future studies with laboratory-confirmed infection diagnosis.

Retrospective review of acute post-tracheostomy complications and contributing risk factors.

OBJECTIVE: Tracheostomy is performed for various indications ranging from prolonged ventilation to airway obstruction. Many factors may play a role in the incidence of complications in the immediate post-operative period including patient-related factors. Chronic obstructive pulmonary disease and asthma are some of the most common pulmonary pathologies in the United States. The relationship between obstructive pulmonary diseases and acute post-tracheostomy complications has been incompletely studied. DESIGN: A retrospective chart review was designed in order to answer these objectives. Medical records were reviewed for the technique used, complications, and contributing patient factors. Post-operative complications were defined as any tracheostomy-related adverse event occurring within 14 days. SETTING: The study took place at an academic comprehensive cancer. PARTICIPANTS: Inclusion criteria included patients from January 2017 through December 2018 who underwent a tracheostomy. Exclusion criteria included presence of stomaplasty, total laryngectomy, and tracheostomies performed at outside hospitals. MAIN OUTCOME MEASURES: Patient factors examined included demographics, comorbidities, and body mass index with the primary outcome measured being the rate of tracheostomy complications. RESULTS: The most common indication for tracheostomy among the 321 patients that met inclusion criteria was airway obstruction or a head and neck cancer surgical procedure. Obstructive sleep apnea was associated with acute complications in bivariate analysis (29.4% complications, p = .003). Chronic obstructive pulmonary disease and asthma were not associated with acute complications in bivariate analysis (11.6% complications, p = .302). Among the secondary outcomes measured, radiation was associated with early complications occurring in post-operative days 0-6 (1.1%, p = .029). CONCLUSION: Patients with obstructive sleep apnea may have a higher risk of acute post-tracheostomy complications that might be due to the patient population at risk for obstructive sleep apnea. Patients with obstructive pulmonary pathologies such as asthma or chronic obstructive pulmonary disorder did not have an elevated risk of complications which is clinically significant when considering the utility of ventilation and tracheostomy in the management of acute respiratory failure secondary to these conditions.

Postlingually Deafened Adult Cochlear Implant Users With Prolonged Recovery From Neural Adaptation at the Level of the Auditory Nerve Tend to Have Poorer Speech Perception Performance.

OBJECTIVE: This study investigated the effects of two temporal response properties of the auditory nerve (i.e., neural adaptation and recovery from neural adaptation) on speech perception performance in postlingually deafened adult cochlear implant (CI) users. DESIGN: Study participants included 18 postlingually deafened adults who were Cochlear Nucleus device users with a full electrode array insertion in the test ear(s). Neural adaptation and adaptation recovery of the auditory nerve (AN) were evaluated using electrophysiological measures of the electrically evoked compound action potential (eCAP). The amount of neural adaptation was quantified by the adaptation index within three time windows: 0 to 8.89 (window 1), 44.44 to 50.00 (window 2), and 94.44 to 100.00 ms (window 3). The speed of neural adaptation was estimated using a two-parameter power law function. To evaluate adaptation recovery of the AN, eCAPs to the last pulse of the 100-ms pulse train were recorded at masker-probe-intervals ranging from 1.054 to 256 ms in logarithmic steps. The amount of adaptation recovery was quantified by the adaptation recovery ratio. The time-constant of adaptation recovery was estimated using an exponential function with up to three components. Speech perception performance was evaluated by measuring consonant-nucleus-consonant (CNC) word scores presented in quiet and in speech-shaped noise at a signal-to-noise ratio (SNR) of +10 dB. One-tailed Pearson Product Moment correlation tests were used (1) to assess the associations among parameters of neural adaptation and adaptation recovery and (2) to evaluate the strength of association between these parameters and CNC word scores measured in quiet and in noise. The contributions of different parameters quantifying neural adaptation and adaptation recovery on speech perception scores were evaluated using multivariable linear regression analyses. RESULTS: The Pearson Product Moment correlation coefficient demonstrated a moderate, negative correlation between the speed of adaptation recovery and CNC word scores measured in quiet and in noise. The speed of adaptation recovery accounted for 14.1% of variability in CNC word scores measured in quiet and 16.7% of variability in CNC word scores measured in noise. The correlation strengths between CNC word scores and the adaptation index, the adaptation recovery ratio and the speed of neural adaptation ranged from negligible to weak. CONCLUSIONS: The speed of adaptation recovery plays a more important role than other features of neural adaptation and adaptation recovery of the AN in speech perception in postlingually deafened adult CI users. Patients with prolonged adaptation recovery tend to show poorer speech perception performance.

Predictive Models for Very Preterm Birth: Developing a Point-of-Care Tool.

OBJECTIVE: The objective of this study was to create three point-of-care predictive models for very preterm birth using variables available at three different time points: prior to pregnancy, at the end of the first trimester, and mid-pregnancy. STUDY DESIGN: This is a retrospective cohort study of 359,396 Ohio Medicaid mothers from 2008 to 2015. The last baby for each mother was included in the final dataset. Births prior to 22 weeks were excluded. Multivariable logistic regression was used to create three models. These models were validated on a cohort that was set aside and not part of the model development. The main outcome measure was birth prior to 32 weeks. RESULTS: The final dataset contained 359,396 live births with 6,516 (1.81%) very preterm births. All models had excellent calibration. Goodness-of-fit tests suggested strong agreement between the probabilities estimated by the model and the actual outcome experience in the data. The mid-pregnancy model had acceptable discrimination with an area under the receiver operator characteristic curve of approximately 0.75 in both the developmental and validation datasets. CONCLUSION: Using data from a large Ohio Medicaid cohort we developed point-of-care predictive models that could be used before pregnancy, after the first trimester, and in mid-pregnancy to estimate the probability of very preterm birth. Future work is needed to determine how the calculator could be used to target interventions to prevent very preterm birth. KEY POINTS: · We developed predictive models for very preterm birth.. · All models showed excellent calibration.. · The models were integrated into a risk calculator..

Parental occupational exposure to pesticides, animals and organic dust and risk of childhood leukemia and central nervous system tumors: Findings from the International Childhood Cancer Cohort Consortium (I4C).

Parental occupational exposures to pesticides, animals and organic dust have been associated with an increased risk of childhood cancer based mostly on case-control studies. We prospectively evaluated parental occupational exposures and risk of childhood leukemia and central nervous system (CNS) tumors in the International Childhood Cancer Cohort Consortium. We pooled data on 329,658 participants from birth cohorts in five countries (Australia, Denmark, Israel, Norway and United Kingdom). Parental occupational exposures during pregnancy were estimated by linking International Standard Classification of Occupations-1988 job codes to the ALOHA+ job exposure matrix. Risk of childhood (<15 years) acute lymphoblastic leukemia (ALL; n = 129), acute myeloid leukemia (AML; n = 31) and CNS tumors (n = 158) was estimated using Cox proportional hazards models to generate hazard ratios (HR) and 95% confidence intervals (CI). Paternal exposures to pesticides and animals were associated with increased risk of childhood AML (herbicides HR = 3.22, 95% CI = 0.97-10.68; insecticides HR = 2.86, 95% CI = 0.99-8.23; animals HR = 3.89, 95% CI = 1.18-12.90), but not ALL or CNS tumors. Paternal exposure to organic dust was positively associated with AML (HR = 2.38 95% CI = 1.12-5.07), inversely associated with ALL (HR = 0.55, 95% CI = 0.31-0.99) and not associated with CNS tumors. Low exposure prevalence precluded evaluation of maternal pesticide and animal exposures; we observed no significant associations with organic dust exposure. This first prospective analysis of pooled birth cohorts and parental occupational exposures provides evidence for paternal agricultural exposures as childhood AML risk factors. The different risks for childhood ALL associated with maternal and paternal organic dust exposures should be investigated further.

Time to Treatment and Mortality during Mandated Emergency Care for Sepsis.

BACKGROUND: In 2013, New York began requiring hospitals to follow protocols for the early identification and treatment of sepsis. However, there is controversy about whether more rapid treatment of sepsis improves outcomes in patients. METHODS: We studied data from patients with sepsis and septic shock that were reported to the New York State Department of Health from April 1, 2014, to June 30, 2016. Patients had a sepsis protocol initiated within 6 hours after arrival in the emergency department and had all items in a 3-hour bundle of care for patients with sepsis (i.e., blood cultures, broad-spectrum antibiotic agents, and lactate measurement) completed within 12 hours. Multilevel models were used to assess the associations between the time until completion of the 3-hour bundle and risk-adjusted mortality. We also examined the times to the administration of antibiotics and to the completion of an initial bolus of intravenous fluid. RESULTS: Among 49,331 patients at 149 hospitals, 40,696 (82.5%) had the 3-hour bundle completed within 3 hours. The median time to completion of the 3-hour bundle was 1.30 hours (interquartile range, 0.65 to 2.35), the median time to the administration of antibiotics was 0.95 hours (interquartile range, 0.35 to 1.95), and the median time to completion of the fluid bolus was 2.56 hours (interquartile range, 1.33 to 4.20). Among patients who had the 3-hour bundle completed within 12 hours, a longer time to the completion of the bundle was associated with higher risk-adjusted in-hospital mortality (odds ratio, 1.04 per hour; 95% confidence interval [CI], 1.02 to 1.05; P<0.001), as was a longer time to the administration of antibiotics (odds ratio, 1.04 per hour; 95% CI, 1.03 to 1.06; P<0.001) but not a longer time to the completion of a bolus of intravenous fluids (odds ratio, 1.01 per hour; 95% CI, 0.99 to 1.02; P=0.21). CONCLUSIONS: More rapid completion of a 3-hour bundle of sepsis care and rapid administration of antibiotics, but not rapid completion of an initial bolus of intravenous fluids, were associated with lower risk-adjusted in-hospital mortality. (Funded by the National Institutes of Health and others.).

Maternal Infection in Pregnancy and Childhood Leukemia: A Systematic Review and Meta-analysis.

OBJECTIVE: To summarize the published evidence regarding the association between maternal infection during pregnancy and childhood leukemia. STUDY DESIGN: In this systematic review and meta-analysis (PROSPERO number, CRD42018087289), we searched PubMed and Embase to identify relevant studies. We included human studies that reported associations of at least one measure of maternal infection during pregnancy with acute lymphoblastic leukemia (ALL) or all childhood leukemias in the offspring. One reviewer extracted the data first using a standardized form, and the second reviewer independently checked the data for accuracy. Two reviewers used the Newcastle-Ottawa Scale to assess the quality of included studies. We conducted random effects meta-analyses to pool the ORs of specific type of infection on ALL and childhood leukemia. RESULTS: This review included 20 studies (ALL, n = 15; childhood leukemia, n = 14) reported in 32 articles. Most (>65%) included studies reported a positive association between infection variables and ALL or childhood leukemia. Among specific types of infection, we found that influenza during pregnancy was associated with higher risk of ALL (pooled OR, 3.64; 95% CI, 1.34-9.90) and childhood leukemia (pooled OR, 1.77; 95% CI, 1.01-3.11). Varicella (pooled OR, 10.19; 95% CI, 1.98-52.39) and rubella (pooled OR, 2.79; 95% CI, 1.16-6.71) infections were also associated with higher childhood leukemia risk. CONCLUSIONS: Our findings suggest that maternal infection during pregnancy may be associated with a higher risk of childhood leukemia.

Assessing the goodness of fit of logistic regression models in large samples: A modification of the Hosmer-Lemeshow test.

Evaluating the goodness of fit of logistic regression models is crucial to ensure the accuracy of the estimated probabilities. Unfortunately, such evaluation is problematic in large samples. Because the power of traditional goodness of fit tests increases with the sample size, practically irrelevant discrepancies between estimated and true probabilities are increasingly likely to cause the rejection of the hypothesis of perfect fit in larger and larger samples. This phenomenon has been widely documented for popular goodness of fit tests, such as the Hosmer-Lemeshow test. To address this limitation, we propose a modification of the Hosmer-Lemeshow approach. By standardizing the noncentrality parameter that characterizes the alternative distribution of the Hosmer-Lemeshow statistic, we introduce a parameter that measures the goodness of fit of a model but does not depend on the sample size. We provide the methodology to estimate this parameter and construct confidence intervals for it. Finally, we propose a formal statistical test to rigorously assess whether the fit of a model, albeit not perfect, is acceptable for practical purposes. The proposed method is compared in a simulation study with a competing modification of the Hosmer-Lemeshow test, based on repeated subsampling. We provide a step-by-step illustration of our method using a model for postneonatal mortality developed in a large cohort of more than 300 000 observations.

The association between birth order and childhood leukemia may be modified by paternal age and birth weight. Pooled results from the International Childhood Cancer Cohort Consortium (I4C).

The "delayed infection hypothesis" states that a paucity of infections in early childhood may lead to higher risks of childhood leukemia (CL), especially acute lymphoblastic leukemia (ALL). Using prospectively collected data from six population-based birth cohorts we studied the association between birth order (a proxy for pathogen exposure) and CL. We explored whether other birth or parental characteristics modify this association. With 2.2 × 106 person-years of follow-up, 185 CL and 136 ALL cases were ascertained. In Cox proportional hazards models, increasing birth order (continuous) was inversely associated with CL and ALL; hazard ratios (HR) = 0.88, 95% confidence interval (CI): (0.77-0.99) and 0.85: (0.73-0.99), respectively. Being later-born was associated with similarly reduced hazards of CL and ALL compared to being first-born; HRs = 0.78: 95% CI: 0.58-1.05 and 0.73: 0.52-1.03, respectively. Successive birth orders were associated with decreased CL and ALL risks (P for trend 0.047 and 0.055, respectively). Multivariable adjustment somewhat attenuated the associations. We found statistically significant and borderline interactions between birth weight (p = 0.024) and paternal age (p = 0.067), respectively, in associations between being later-born and CL, with the lowest risk observed for children born at <3 kg with fathers aged 35+ (HR = 0.18, 95% CI: 0.06-0.50). Our study strengthens the theory that increasing birth order confers protection against CL and ALL risks, but suggests that this association may be modified among subsets of children with different characteristics, notably advanced paternal age and lower birth weight. It is unclear whether these findings can be explained solely by infectious exposures.

Understanding of interaction (subgroup) analysis in clinical trials.

BACKGROUND: When the treatment effect on the outcome of interest is influenced by a baseline/demographic factor, investigators say that an interaction is present. In randomized clinical trials (RCTs), this type of analysis is typically referred to as subgroup analysis. Although interaction (or subgroup) analyses are usually stated as a secondary study objective, it is not uncommon that these results lead to changes in treatment protocols or even modify public health policies. Nonetheless, recent reviews have indicated that their proper assessment, interpretation and reporting remain challenging. RESULTS: Therefore, this article provides an overview of these challenges, to help investigators find the best strategy for application of interaction analyses on binary outcomes in RCTs. Specifically, we discuss the key points of formal interaction testing, including the estimation of both additive and multiplicative interaction effects. We also provide recommendations that, if adhered to, could increase the clarity and the completeness of reports of RCTs. CONCLUSION: Altogether, this article provides a brief non-statistical guide for clinical investigators on how to perform, interpret and report interaction (subgroup) analyses in RCTs.

Mortality Changes Associated with Mandated Public Reporting for Sepsis. The Results of the New York State Initiative.

RATIONALE: In 2013, the New York State Department of Health (NYSDOH) began a mandatory state-wide initiative to improve early recognition and treatment of severe sepsis and septic shock. OBJECTIVES: This study examines protocol initiation, 3-hour and 6-hour sepsis bundle completion, and risk-adjusted hospital mortality among adult patients with severe sepsis and septic shock. METHODS: Cohort analysis included all patients from all 185 hospitals in New York State reported to the NYSDOH from April 1, 2014, to June 30, 2016. A total of 113,380 cases were submitted to NYSDOH, of which 91,357 hospitalizations from 183 hospitals met study inclusion criteria. NYSDOH required all hospitals to submit and follow evidence-informed protocols (including elements of 3-h and 6-h sepsis bundles: lactate measurement, early blood cultures and antibiotic administration, fluids, and vasopressors) for early identification and treatment of severe sepsis or septic shock. MEASUREMENTS AND MAIN RESULTS: Compliance with elements of the sepsis bundles and risk-adjusted mortality were studied. Of 91,357 patients, 74,293 (81.3%) had the sepsis protocol initiated. Among these individuals, 3-hour bundle compliance increased from 53.4% to 64.7% during the study period (P < 0.001), whereas among those eligible for the 6-hour bundle (n = 35,307) compliance increased from 23.9% to 30.8% (P < 0.001). Risk-adjusted mortality decreased from 28.8% to 24.4% (P < 0.001) in patients among whom a sepsis protocol was initiated. Greater hospital compliance with 3-hour and 6-hour bundles was associated with shorter length of stay and lower risk and reliability-adjusted mortality. CONCLUSIONS: New York's statewide initiative increased compliance with sepsis-performance measures. Risk-adjusted sepsis mortality decreased during the initiative and was associated with increased hospital-level compliance.

The New York Sepsis Severity Score: Development of a Risk-Adjusted Severity Model for Sepsis.

OBJECTIVES: In accordance with Rory's Regulations, hospitals across New York State developed and implemented protocols for sepsis recognition and treatment to reduce variations in evidence informed care and preventable mortality. The New York Department of Health sought to develop a risk assessment model for accurate and standardized hospital mortality comparisons of adult septic patients across institutions using case-mix adjustment. DESIGN: Retrospective evaluation of prospectively collected data. PATIENTS: Data from 43,204 severe sepsis and septic shock patients from 179 hospitals across New York State were evaluated. SETTINGS: Prospective data were submitted to a database from January 1, 2015, to December 31, 2015. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Maximum likelihood logistic regression was used to estimate model coefficients used in the New York State risk model. The mortality probability was estimated using a logistic regression model. Variables to be included in the model were determined as part of the model-building process. Interactions between variables were included if they made clinical sense and if their p values were less than 0.05. Model development used a random sample of 90% of available patients and was validated using the remaining 10%. Hosmer-Lemeshow goodness of fit p values were considerably greater than 0.05, suggesting good calibration. Areas under the receiver operator curve in the developmental and validation subsets were 0.770 (95% CI, 0.765-0.775) and 0.773 (95% CI, 0.758-0.787), respectively, indicating good discrimination. Development and validation datasets had similar distributions of estimated mortality probabilities. Mortality increased with rising age, comorbidities, and lactate. CONCLUSIONS: The New York Sepsis Severity Score accurately estimated the probability of hospital mortality in severe sepsis and septic shock patients. It performed well with respect to calibration and discrimination. This sepsis-specific model provides an accurate, comprehensive method for standardized mortality comparison of adult patients with severe sepsis and septic shock.

Who owns guns and how do they keep them? The influence of household characteristics on firearms ownership and storage practices in the United States.

Our paper aims to describe firearm-related behavior among American households and to quantify the influence of household characteristics on the probability of firearms possession and storage practices. Applying logistic regression techniques to data from the 2004 Behavioral Risk Factor Surveillance Survey (BRFSS), we use separate models to estimate the effect of an array of respondent demographic characteristics factors on the likelihood that households will have a gun at home and, if so, whether they will keep it at either of two levels of risk. We find that rates of firearm ownership vary widely by household characteristics, including the state in which they reside. Simultaneously controlling for all of these factors scarcely diminishes variation in odds for ownership. Differences in the likelihood that owners will store guns unsafely are narrower and significant for fewer factors. Having children in the home scarcely affects the propensity to possess firearms but greatly reduces the chances a domestic firearm will be stored loaded and unsecured. Our findings support a consensus on the demographics of ownership but show more and stronger predictors of storage behavior than previous work. Differing dynamics of ownership and storage reveal the existence of two regional gun cultures. From these findings, we conclude that to mitigate mortality risks associated with guns in the home, encouraging safer storage by owners may be as effective as controlling sales. States and localities should test a range of promising but largely unproven interventions.

The International Childhood Cancer Cohort Consortium (I4C): A research platform of prospective cohorts for studying the aetiology of childhood cancers.

BACKGROUND: Childhood cancer is a rare but leading cause of morbidity and mortality. Established risk factors, accounting for <10% of incidence, have been identified primarily from case-control studies. However, recall, selection and other potential biases impact interpretations particularly, for modest associations. A consortium of pregnancy and birth cohorts (I4C) was established to utilise prospective, pre-diagnostic exposure assessments and biological samples. METHODS: Eligibility criteria, follow-up methods and identification of paediatric cancer cases are described for cohorts currently participating or planning future participation. Also described are exposure assessments, harmonisation methods, biological samples potentially available for I4C research, the role of the I4C data and biospecimen coordinating centres and statistical approaches used in the pooled analyses. RESULTS: Currently, six cohorts recruited over six decades (1950s-2000s) contribute data on 388 120 mother-child pairs. Nine new cohorts from seven countries are anticipated to contribute data on 627 500 additional projected mother-child pairs within 5 years. Harmonised data currently includes over 20 "core" variables, with notable variability in mother/child characteristics within and across cohorts, reflecting in part, secular changes in pregnancy and birth characteristics over the decades. CONCLUSIONS: The I4C is the first cohort consortium to have published findings on paediatric cancer using harmonised variables across six pregnancy/birth cohorts. Projected increases in sample size, expanding sources of exposure data (eg, linkages to environmental and administrative databases), incorporation of biological measures to clarify exposures and underlying molecular mechanisms and forthcoming joint efforts to complement case-control studies offer the potential for breakthroughs in paediatric cancer aetiologic research.

Association Between the New York Sepsis Care Mandate and In-Hospital Mortality for Pediatric Sepsis.

Importance: The death of a pediatric patient with sepsis motivated New York to mandate statewide sepsis treatment in 2013. The mandate included a 1-hour bundle of blood cultures, broad-spectrum antibiotics, and a 20-mL/kg intravenous fluid bolus. Whether completing the bundle elements within 1 hour improves outcomes is unclear. Objective: To determine the risk-adjusted association between completing the 1-hour pediatric sepsis bundle and individual bundle elements with in-hospital mortality. Design, Settings, and Participants: Statewide cohort study conducted from April 1, 2014, to December 31, 2016, in emergency departments, inpatient units, and intensive care units across New York State. A total of 1179 patients aged 18 years and younger with sepsis and septic shock reported to the New York State Department of Health who had a sepsis protocol initiated were included. Exposures: Completion of a 1-hour sepsis bundle within 1 hour compared with not completing the 1-hour sepsis bundle within 1 hour. Main Outcomes and Measures: Risk-adjusted in-hospital mortality. Results: Of 1179 patients with sepsis reported at 54 hospitals (mean [SD] age, 7.2 [6.2] years; male, 54.2%; previously healthy, 44.5%; diagnosed as having shock, 68.8%), 139 (11.8%) died. The entire sepsis bundle was completed in 1 hour in 294 patients (24.9%). Antibiotics were administered to 798 patients (67.7%), blood cultures were obtained in 740 patients (62.8%), and the fluid bolus was completed in 548 patients (46.5%) within 1 hour. Completion of the entire bundle within 1 hour was associated with lower risk-adjusted odds of in-hospital mortality (odds ratio [OR], 0.59 [95% CI, 0.38 to 0.93], P = .02; predicted risk difference [RD], 4.0% [95% CI, 0.9% to 7.0%]). However, completion of each individual bundle element within 1 hour was not significantly associated with lower risk-adjusted mortality (blood culture: OR, 0.73 [95% CI, 0.51 to 1.06], P = .10; RD, 2.6% [95% CI, -0.5% to 5.7%]; antibiotics: OR, 0.78 [95% CI, 0.55 to 1.12], P = .18; RD, 2.1% [95% CI, -1.1% to 5.2%], and fluid bolus: OR, 0.88 [95% CI, 0.56 to 1.37], P = .56; RD, 1.1% [95% CI, -2.6% to 4.8%]). Conclusions and Relevance: In New York State following a mandate for sepsis care, completion of a sepsis bundle within 1 hour compared with not completing the 1-hour sepsis bundle within 1 hour was associated with lower risk-adjusted in-hospital mortality among patients with pediatric sepsis and septic shock.

Surviving Sepsis Campaign: association between performance metrics and outcomes in a 7.5-year study.

PURPOSE: To determine the association between compliance with the Surviving Sepsis Campaign (SSC) performance bundles and mortality. DESIGN: Compliance with the SSC performance bundles, which are based on the 2004 SSC guidelines, was measured in 29,470 subjects entered into the SSC database from January 1, 2005, through June 30, 2012. Compliance was defined as evidence that all bundle elements were achieved. SETTING: Two hundred eighteen community, academic, and tertiary care hospitals in the United States, South America, and Europe. PATIENTS: Patients from the emergency department, medical and surgical wards, and ICU who met diagnosis criteria for severe sepsis and septic shock. METHODS: A multifaceted, collaborative change intervention aimed at facilitating adoption of the SSC resuscitation and management bundles was introduced. Compliance with the SSC bundles and associated mortality rate was the primary outcome variable. RESULTS: Overall lower mortality was observed in high (29.0%) versus low (38.6%) resuscitation bundle compliance sites (p < 0.001) and between high (33.4%) and low (32.3%) management bundle compliance sites (p = 0.039). Hospital mortality rates dropped 0.7% per site for every three months (quarter) of participation (p < 0.001). Hospital and intensive care unit length of stay decreased 4% (95% CI: 1% - 7%; p = 0.012) for every 10% increase in site compliance with the resuscitation bundle. CONCLUSIONS: This analysis demonstrates that increased compliance with sepsis performance bundles was associated with a 25% relative risk reduction in mortality rate. Every 10% increase in compliance and additional quarter of participation in the SSC initiative was associated with a significant decrease in the odds ratio for hospital mortality. These results demonstrate that performance metrics can drive change in clinical behavior, improve quality of care, and may decrease mortality in patients with severe sepsis and septic shock.

Birthweight and Childhood Cancer: Preliminary Findings from the International Childhood Cancer Cohort Consortium (I4C).

BACKGROUND: Evidence relating childhood cancer to high birthweight is derived primarily from registry and case-control studies. We aimed to investigate this association, exploring the potential modifying roles of age at diagnosis and maternal anthropometrics, using prospectively collected data from the International Childhood Cancer Cohort Consortium. METHODS: We pooled data on infant and parental characteristics and cancer incidence from six geographically and temporally diverse member cohorts [the Avon Longitudinal Study of Parents and Children (UK), the Collaborative Perinatal Project (USA), the Danish National Birth Cohort (Denmark), the Jerusalem Perinatal Study (Israel), the Norwegian Mother and Child Cohort Study (Norway), and the Tasmanian Infant Health Survey (Australia)]. Birthweight metrics included a continuous measure, deciles, and categories (≥ 4.0 vs. < 4.0 kilogram). Childhood cancer (377 cases diagnosed prior to age 15 years) risk was analysed by type (all sites, leukaemia, acute lymphoblastic leukaemia, and non-leukaemia) and age at diagnosis. We estimated hazard ratios (HR) and 95% confidence intervals (CI) from Cox proportional hazards models stratified by cohort. RESULTS: A linear relationship was noted for each kilogram increment in birthweight adjusted for gender and gestational age for all cancers [HR = 1.26; 95% CI 1.02, 1.54]. Similar trends were observed for leukaemia. There were no significant interactions with maternal pre-pregnancy overweight or pregnancy weight gain. Birthweight ≥ 4.0 kg was associated with non-leukaemia cancer among children diagnosed at age ≥ 3 years [HR = 1.62; 95% CI 1.06, 2.46], but not at younger ages [HR = 0.7; 95% CI 0.45, 1.24, P for difference = 0.02]. CONCLUSION: Childhood cancer incidence rises with increasing birthweight. In older children, cancers other than leukaemia are particularly related to high birthweight. Maternal adiposity, currently widespread, was not demonstrated to substantially modify these associations. Common factors underlying foetal growth and carcinogenesis need to be further explored.

Sepsis severity score: an internationally derived scoring system from the surviving sepsis campaign database*.

OBJECTIVE: As the Surviving Sepsis Campaign was assessing patient-level data over multiple countries, we sought to evaluate the use of a pragmatic and parsimonious severity-of-illness scoring system for patients with sepsis in an attempt to provide appropriate comparisons with practical application. DESIGN: Prospective, observational evaluation. PATIENTS: Data from 23,438 patients with suspected or confirmed sepsis from 218 hospitals in 18 countries were evaluated. SETTING: This analysis was conducted on prospective data submitted to a database from January 2005 through March 2010. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Maximum likelihood logistic regression was used to estimate model coefficients, and these were then used to develop a Sepsis Severity Score. The probability of hospital mortality was estimated using the Sepsis Severity Score as the sole variable in a logistic regression model. Univariable logistic regression determined which variables were included in the multivariable predictor model. The scale of continuous variables was assessed using fractional polynomials. Two-way interactions between variables were considered for model inclusion if the interaction p value is less than 0.05. The prediction model was developed based on randomly selecting 90% of available patients and was validated on the remaining 10%, as well as by using a bootstrapping technique. The p values for the Hosmer-Lemeshow goodnessof-fit statistic in the developmental and validation datasets were considerably greater than 0.05, suggesting good calibration. Development and validation areas under the receiver operator curve curves were 0.736 and 0.748, respectively. Observed and estimated probabilities of hospital mortality for the total population were both 0.334. The validation and the developmental datasets were gradually compared over deciles of predicted mortality and found to be very similar. CONCLUSION: The Sepsis Severity Score accurately estimated the probability of hospital mortality in severe sepsis and septic shock patients. It performed well with respect to calibration and discrimination, which remained consistent over deciles. It functioned well over international geographic regions. This robust, population-specific evaluation of international severe sepsis patients provides an effective and accurate mortality estimate allowing for appropriate quality comparisons with practical clinical and research application.

Maternal-infant relationship quality and risk of obesity at age 5.5 years in a national US cohort.

BACKGROUND: Poor quality relationships between mothers and toddlers have been associated with higher risk for childhood obesity, but few prospective studies of obesity have assessed maternal-child relationship quality in infancy. In addition it is not known whether the increased risk is associated with the mother's or the child's contribution to the relationship quality. METHODS: We analyzed data (n = 5650) from the Early Childhood Longitudinal Study, Birth Cohort, a national study of U.S. children born in 2001 and followed until they entered kindergarten. At 9 months of age, the Nursing Child Assessment Teaching Scale (NCATS) was used to assess the quality of observed playtime interactions between mothers and infants, yielding separate scores for maternal and infant behaviors. Obesity (BMI ≥95th percentile) at age 5.5 years was based on measured weight and height. RESULTS: The prevalence (95% confidence interval) of obesity at 5.5 years of age was higher among children in the lowest quartile of maternal NCATS score (20.2% [95% CI: 17.2%, 23.2%]) than in the highest quartile (13.9% [11.3%, 16.5%]), but maternal NCATS score was not significantly associated with obesity after adjustment for race/ethnicity, maternal education and household income. The prevalence of obesity at 5.5 years of age was similar among children in the lowest quartile of infant NCATS score (17.4% [14.4%, 20.3%]) and in the highest quartile (17.6% 14.4%, 20.8%]), and was not changed with covariate adjustment. CONCLUSIONS: Maternal-infant relationship quality, assessed by direct observation at 9 months of age in a national sample, was not associated with an increased risk of obesity at age 5.5 years after controlling for sociodemographic characteristics.