<p><strong>BACKGROUND: </strong>Surface mining has become a significant method of coal mining in the Central Appalachian region of the eastern United States alongside the traditional underground mining. Concerns have been raised about the health effects of this surface mining, particularly mountaintop removal mining where coal is mined upon steep mountaintops by removing the mountaintop through clearcutting forests and explosives.</p>

<p><strong>METHODS: </strong>We used a control group design with a pretest and a posttest to assess the associations of surface mining in Central Appalachia with low birth weight and other adverse birth outcomes. The pretest period is 1977-1989, a period of low surface mining activity. We consider three posttest periods: 1990-1998, 1999-2011 and 2012-2017, with 1999-2011 as the primary analysis and the other periods as secondary analyses. Surface mining in Central Appalachia increased after 1989, partly resulting from the Clean Air Act Amendments of 1990 which made surface mining more financially attractive. For the primary analysis, we fit a logistic regression model of the primary outcome (low birth weight, &lt;2500 grams) on dummy variables for county and year; individual level maternal/infant covariates (maternal race, maternal age, infant sex and whether birth was a multiple birth); and the amount of surface mining during the year of the birth in the maternal county of residence.</p>

<p><strong>RESULTS: </strong>Our analysis sample consisted of 783,328 infants -- 482,284 infants born from 1977-2017 to women residing in substantial surface mining activity counties and 301,044 infants born from 1977-2017 to women residing in matched control counties. Compared to the pre-period of low surface mining from 1977-1989, for the primary analysis post-test period of 1999-2011, there was an estimated relative increase in low birth weight in surface mining counties compared to matched control counties that was not statistically significant (odds ratio for a 5 percentage point increase in area disturbed by surface mining: 1.07, 95% confidence interval (0.96, 1.20), p-value: .22). For the secondary analysis post-test period of 1990-1998, there was no increase (odds ratio: 0.91, 95% confidence interval: (0.74, 1.13), p-value: .41). For the secondary analysis post-test period of 2012-2017, there was a statistically significant relative increase (odds ratio: 1.28, 95% confidence interval: (1.08, 1.50), p-value: .004). Qualitatively similar results were found for the outcomes of very low birth weight, preterm birth and small-for-gestational age.</p>

<p><strong>CONCLUSIONS: </strong>We examined the hypothesis that surface mining activity in Central Appalachia contributes to low birth weight using an observational study. We found evidence in secondary analyses that surface mining was associated with low birth weight in the 2012-2017 time period and potentially beginning in the early to mid 2000's. Evidence for an association was not found prior to 2000. A potential explanation for this pattern of association is that surface mining caused an increase in low birth weight but its onset was delayed. Future research is needed to clarify the findings and if replicated, identify the mechanism necessary to mitigate the impacts of mining on adverse birth outcomes.</p>

<p>We retrospectively studied the effect of introducing procalcitonin into clinical practice on antibiotic use within a large academic pediatric intensive care unit. In the absence of a standardized algorithm, availability of the procalcitonin assay did not reduce the frequency of antibiotic initiations or the continuation of antibiotics for greater than 72 hours.</p>

<p><strong>OBJECTIVE: </strong>Delayed antimicrobial therapy in sepsis is associated with increased hospital mortality, but the impact of antimicrobial timing on long-term outcomes is unknown. We tested the hypothesis that hourly delays to antimicrobial therapy are associated with 1-year mortality in pediatric severe sepsis.</p>

<p><strong>DESIGN: </strong>Retrospective observational study.</p>

<p><strong>SETTING: </strong>Quaternary academic pediatric intensive care unit (PICU) from February 1, 2012 to June 30, 2013.</p>

<p><strong>PATIENTS: </strong>One hundred sixty patients aged ≤21 years treated for severe sepsis.</p>

<p><strong>INTERVENTIONS: </strong>None.</p>

<p><strong>MEASUREMENTS AND MAIN RESULTS: </strong>We tested the association of hourly delays from sepsis recognition to antimicrobial administration with 1-year mortality using multivariable Cox and logistic regression. Overall 1-year mortality was 24% (39 patients), of whom 46% died after index PICU discharge. Median time from sepsis recognition to antimicrobial therapy was 137 min (IQR 65-287). After adjusting for severity of illness and comorbid conditions, hourly delays up to 3 h were not associated with 1-year mortality. However, increased 1-year mortality was evident in patients who received antimicrobials ≤1 h (aOR 3.8, 95% CI 1.2, 11.7) or &gt;3 h (aOR 3.5, 95% CI 1.3, 9.8) compared with patients who received antimicrobials within 1 to 3 h from sepsis recognition. For the subset of patients who survived index PICU admission, antimicrobial therapy ≤1 h was also associated with increased 1-year mortality (aOR 5.5, 95% CI 1.1, 27.4), while antimicrobial therapy &gt;3 h was not associated with 1-year mortality (aOR 2.2, 95% CI 0.5, 11.0).</p>

<p><strong>CONCLUSIONS: </strong>Hourly delays to antimicrobial therapy, up to 3 h, were not associated with 1-year mortality in pediatric severe sepsis in this study. The finding that antimicrobial therapy ≤1 h from sepsis recognition was associated with increased 1-year mortality should be regarded as hypothesis-generating for future studies.</p>

<p><strong>OBJECTIVE: </strong>To test the hypothesis that resuscitation with balanced fluids (lactated Ringer [LR]) is associated with improved outcomes compared with normal saline (NS) in pediatric sepsis.</p>

<p><strong>STUDY DESIGN: </strong>We performed matched analyses using data from 12 529 patients &lt;18 years of age with severe sepsis/septic shock at 382 US hospitals between 2000 and 2013 to compare outcomes with vs without LR as part of initial resuscitation. Patients receiving LR were matched 1:1 to patients receiving only NS (NS group), including separate matches for any (LR-any group) or exclusive (LR-only group) LR use. Outcomes included 30-day hospital mortality, acute kidney injury, new dialysis, and length of stay.</p>

<p><strong>RESULTS: </strong>The LR-any group was older, received larger crystalloid volumes, and was less likely to have malignancies than the NS group. After matching, mortality was not different between LR-any (7.2%) and NS (7.9%) groups (risk ratio 0.99, 95% CI 0.98, 1.01; P = .20). There were no differences in secondary outcomes except longer hospital length of stay in LR-any group (absolute difference 2.4, 95% CI 1.4, 5.0 days; P &lt; .001). Although LR was preferentially used as adjunctive fluid with large-volume resuscitation or first-line fluid in patients with lower illness severity, outcomes were not different after matching stratified by volume and proportionate LR utilization, including for patients in the LR-only group.</p>

<p><strong>CONCLUSIONS: </strong>Balanced fluid resuscitation with LR was not associated with improved outcomes compared with NS in pediatric sepsis. Although the current practice of NS resuscitation is justified, selective LR use necessitates a prospective trial to definitively determine comparative effectiveness among crystalloids.</p>