Frequency of bystander exposure to antibiotics for enteropathogenic bacteria among young children in low-resource settings.

Children in low-resource settings carry enteric pathogens asymptomatically and are frequently treated with antibiotics, resulting in opportunities for pathogens to be exposed to antibiotics when not the target of treatment (i.e., bystander exposure). We quantified the frequency of bystander antibiotic exposures for enteric pathogens and estimated associations with resistance among children in eight low-resource settings. We analyzed 15,697 antibiotic courses from 1,715 children aged 0 to 2 y from the MAL-ED birth cohort. We calculated the incidence of bystander exposures and attributed exposures to respiratory and diarrheal illnesses. We associated bystander exposure with phenotypic susceptibility of E. coli isolates in the 30 d following exposure and at the level of the study site. There were 744.1 subclinical pathogen exposures to antibiotics per 100 child-years. Enteroaggregative Escherichia coli was the most frequently exposed pathogen, with 229.6 exposures per 100 child-years. Almost all antibiotic exposures for Campylobacter (98.8%), enterotoxigenic E. coli (95.6%), and typical enteropathogenic E. coli (99.4%), and the majority for Shigella (77.6%), occurred when the pathogens were not the target of treatment. Respiratory infections accounted for half (49.9%) and diarrheal illnesses accounted for one-fourth (24.6%) of subclinical enteric bacteria exposures to antibiotics. Bystander exposure of E. coli to class-specific antibiotics was associated with the prevalence of phenotypic resistance at the community level. Antimicrobial stewardship and illness-prevention interventions among children in low-resource settings would have a large ancillary benefit of reducing bystander selection that may contribute to antimicrobial resistance.

Early Patient Discharge in Selected Patients is Not Associated With Higher Readmission After Major Abdominal Operations.

OBJECTIVE: Our objective was to examine the associations between early discharge and readmission after major abdominal operations. BACKGROUND: Advances in patient care resulted in earlier patient discharge after complex abdominal operations. Whether early discharge is associated with patient readmissions remains controversial. METHODS: Patients who had colorectal, liver, and pancreas operations abstracted in 2011-2017 American College of Surgeons National Surgical Quality Improvement Program Participant Use Data Files were included. Patient readmission was stratified by 6 operative groups. Patients who were discharged before median discharge date within each operative group were categorized as an early discharge. Analyses tested associations between early discharge and likelihood of 30-day postoperative unplanned readmission. RESULTS: A total of 364,609 patients with major abdominal operations were included. Individual patient groups and corresponding median day of discharge were: laparoscopic colectomy (n = 152,575; median = 4), open colectomy (n =137,462; median = 7), laparoscopic proctectomy (n = 12,238; median = 5), open proctectomy (n = 24,925; median = 6), major hepatectomy (n = 9,805; median = 6), pancreatoduodenectomy (n = 27,604; median = 8). Early discharge was not associated with an increase in proportion of readmissions in any operative group. Early discharge was associated with a decrease in average proportion of patient readmissions compared to patients discharged on median date in each of the operative groups: laparoscopic colectomy 6% versus 8%, open colectomy 11% versus 14%, laparoscopic proctectomy 13% versus 16%, open proctectomy 13% vs 17%, major hepatectomy 8% versus 12%, pancreatoduodenectomy 16% versus 20% (all P ≤ 0.02). Serious morbidity composite was significantly lower in patients who were discharged early than those who were not in each operative group (all P < 0.001). CONCLUSIONS: Early discharge in selected patients after major abdominal operations is associated with lower, and not higher, rate of 30-day unplanned readmission.

Errors in Surgery: A Case Control Study.

OBJECTIVE: While errors can harm patients they remain poorly studied. This study characterized errors in the care of surgical patients and examined the association of errors with morbidity and mortality. BACKGROUND: Errors have been reported to cause <10% or >60% of adverse events. Such discordant results underscore the need for further exploration of the relationship between error and adverse events. METHODS: Patients with operations performed at a single institution and abstracted into the American College of Surgeons National Surgical Quality Improvement Program from January 1, 2018, to December 31, 2018 were examined. This matched case control study comprised cases who experienced a postoperative morbidity or mortality. Controls included patients without morbidity or mortality, matched 2:1 using age (±10 years), sex, and Current Procedural Terminology (CPT) group. Two faculty surgeons independently reviewed records for each case and control patient to identify diagnostic, technical, judgment, medication, system, or omission errors. A conditional multivariable logistic regression model examined the association between error and morbidity. RESULTS: Of 1899 patients, 170 were defined as cases who experienced a morbidity or mortality. The majority of cases (n=93; 55%) had at least 1 error; of the 329 matched control patients, 112 had at least 1 error (34%). Technical errors occurred most often among both cases (40%) and controls (23%). Logistic regression demonstrated a strong independent relationship between error and morbidity (odds ratio=2.67, 95% confidence interval: 1.64-4.35, P <0.001). CONCLUSION: Errors in surgical care were associated with postoperative morbidity. Reducing errors requires measurement of errors.

Mediastinal Masses, Anesthetic Interventions, and Airway Compression in Adults: A Prospective Observational Study.

BACKGROUND: Central airway occlusion is a feared complication of general anesthesia in patients with mediastinal masses. Maintenance of spontaneous ventilation and avoiding neuromuscular blockade are recommended to reduce this risk. Physiologic arguments supporting these recommendations are controversial and direct evidence is lacking. The authors hypothesized that, in adult patients with moderate to severe mediastinal mass-mediated tracheobronchial compression, anesthetic interventions including positive pressure ventilation and neuromuscular blockade could be instituted without compromising central airway patency. METHODS: Seventeen adult patients with large mediastinal masses requiring general anesthesia underwent awake intubation followed by continuous video bronchoscopy recordings of the compromised portion of the airway during staged induction. Assessments of changes in anterior-posterior airway diameter relative to baseline (awake, spontaneous ventilation) were performed using the following patency scores: unchanged = 0; 25 to 50% larger = +1; more than 50% larger = +2; 25 to 50% smaller = -1; more than 50% smaller = -2. Assessments were made by seven experienced bronchoscopists in side-by-side blinded and scrambled comparisons between (1) baseline awake, spontaneous breathing; (2) anesthetized with spontaneous ventilation; (3) anesthetized with positive pressure ventilation; and (4) anesthetized with positive pressure ventilation and neuromuscular blockade. Tidal volumes, respiratory rate, and inspiratory/expiratory ratio were similar between phases. RESULTS: No significant change from baseline was observed in the mean airway patency scores after the induction of general anesthesia (0 [95% CI, 0 to 0]; P = 0.953). The mean airway patency score increased with the addition of positive pressure ventilation (0 [95% CI, 0 to 1]; P = 0.024) and neuromuscular blockade (1 [95% CI, 0 to 1]; P < 0.001). No patient suffered airway collapse or difficult ventilation during any anesthetic phase. CONCLUSIONS: These observations suggest a need to reassess prevailing assumptions regarding positive pressure ventilation and/or paralysis and mediastinal mass-mediated airway collapse, but do not prove that conventional (nonstaged) inductions are safe for such patients.

Duration of Postdiarrheal Enteric Pathogen Carriage in Young Children in Low-resource Settings.

BACKGROUND: Prolonged enteropathogen shedding after diarrhea complicates the identification of etiology in subsequent episodes and is an important driver of pathogen transmission. A standardized approach has not been applied to estimate the duration of shedding for a wide range of pathogens. METHODS: We used a multisite birth cohort of children 0-24 months of age from whom diarrheal and monthly nondiarrheal stools were previously tested by quantitative polymerase chain reaction for 29 enteropathogens. We modeled the probability of detection of the etiologic pathogen before and after diarrhea using a log-normal accelerated failure time survival model and estimated the median duration of pathogen carriage as well as differences in subclinical pathogen carriage 60 days after diarrhea onset in comparison to a prediarrhea baseline. RESULTS: We analyzed 3247 etiologic episodes of diarrhea for the 9 pathogens with the highest attributable burdens of diarrhea. The median duration of postdiarrheal carriage varied widely by pathogen, from about 1 week for rotavirus (median, 8.1 days [95% confidence interval {CI}, 6.2-9.6]) to >1 month for Cryptosporidium (39.5 days [95% CI, 30.6-49.0]). The largest increases in subclinical pathogen carriage before and after diarrhea were seen for Cryptosporidium (prevalence difference between 30 days prior and 60 days after diarrhea onset, 0.30 [95% CI, .23-.39]) and Shigella (prevalence difference, 0.21 [95% CI, .16-.27]). CONCLUSIONS: Postdiarrheal shedding was widely variable between pathogens, with strikingly prolonged shedding seen for Cryptosporidium and Shigella. Targeted antimicrobial therapy and vaccination for these pathogens may have a relatively large impact on transmission.

The Clinical Presentation of Culture-positive and Culture-negative, Quantitative Polymerase Chain Reaction (qPCR)-Attributable Shigellosis in the Global Enteric Multicenter Study and Derivation of a Shigella Severity Score: Implications for Pediatric Shigella Vaccine Trials.

BACKGROUND: Shigella is a leading cause of childhood diarrhea and target for vaccine development. Microbiologic and clinical case definitions are needed for pediatric field vaccine efficacy trials. METHODS: We compared characteristics of moderate to severe diarrhea (MSD) cases in the Global Enteric Multicenter Study (GEMS) between children with culture positive Shigella to those with culture-negative, quantitative polymerase chain reaction (qPCR)-attributable Shigella (defined by an ipaH gene cycle threshold <27.9). Among Shigella MSD cases, we determined risk factors for death and derived a clinical severity score. RESULTS: Compared to culture-positive Shigella MSD cases (n = 745), culture-negative/qPCR-attributable Shigella cases (n = 852) were more likely to be under 12 months, stunted, have a longer duration of diarrhea, and less likely to have high stool frequency or a fever. There was no difference in dehydration, hospitalization, or severe classification from a modified Vesikari score. Twenty-two (1.8%) Shigella MSD cases died within the 14-days after presentation to health facilities, and 59.1% of these deaths were in culture-negative cases. Age <12 months, diarrhea duration prior to presentation, vomiting, stunting, wasting, and hospitalization were associated with mortality. A model-derived score assigned points for dehydration, hospital admission, and longer diarrhea duration but was not significantly better at predicting 14-day mortality than a modified Vesikari score. CONCLUSIONS: A composite severity score consistent with severe disease or dysentery may be a pragmatic clinical endpoint for severe shigellosis in vaccine trials. Reliance on culture for microbiologic confirmation may miss a substantial number of Shigella cases but is currently required to measure serotype specific immunity.

Meaningful Patient-centered Outcomes 1 Year Following Cardiac Surgery.

OBJECTIVE: To evaluate meaningful, patient-centered outcomes including alive-at-home status and patient-reported quality of life 1 year after cardiac surgery. BACKGROUND: Long-term patient-reported quality of life after cardiac surgery is not well understood. Current operative risk models and quality metrics focus on short-term outcomes. METHODS: In this combined retrospective/prospective study, cardiac surgery patients at an academic institution (2014-2015) were followed to obtain vital status, living location, and patient-reported outcomes (PROs) at 1 year using the NIH Patient-Reported Outcomes Measurement Information System (PROMIS). We assessed the impact of cardiac surgery, discharge location, and Society of Thoracic Surgeons perioperative predicted risk of morbidity or mortality on 1-year outcomes. RESULTS: A total of 782 patients were enrolled; 84.1% (658/782) were alive-at-home at 1 year. One-year PROMIS scores were global physical health (GPH) = 48.8 ±â€Š10.2, global mental health (GMH) = 51.2 ±â€Š9.6, and physical functioning (PF) = 45.5 ±â€Š10.2 (general population reference = 50 ±â€Š10). All 3 PROMIS domains at 1 year were significantly higher compared with preoperative scores (GPH: 41.7 ±â€Š8.5, GMH: 46.9 ±â€Š7.9, PF: 39.6 ±â€Š9.0; all P < 0.001). Eighty-two percent of patients discharged to a facility were alive-at-home at 1 year. These patients, however, had significantly lower 1-year scores (difference: GPH = -5.1, GMH = -5.1, PF = -7.9; all P < 0.001). Higher Society of Thoracic Surgeons perioperative predicted risk was associated with significantly lower PRO at 1 year (P < 0.001). CONCLUSIONS: Cardiac surgery results in improved PROMIS scores at 1 year, whereas discharge to a facility and increasing perioperative risk correlate with worse long-term PRO. One-year alive-at-home status and 1-year PRO are meaningful, patient-centered metrics that help define long-term quality and the benefit of cardiac surgery.

Determining the Association Between Unplanned Reoperation and Readmission in Selected General Surgery Operations.

BACKGROUND: Unplanned reoperations and unplanned readmissions can increase morbidity and mortality. Few studies however, have explored the association of reoperation and readmission among general surgery patients. Our aim was to examine this relationship in selected abdominal operations. METHODS: Data from the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) Participant Use Data Files from 2014 to 2018 were utilized. Six groups of operations, defined by ACS NSQIP procedure codes for ventral hernia repair, colectomy, appendectomy, proctectomy, small bowel resection, and gastrectomy, were assessed. Patients discharged ≤ 14 days after operation were included in the study. This time period was selected to reduce ACS NSQIP 30 day post-surgery follow-up bias. Unplanned reoperations were defined as those occurring during the index hospitalization. The primary outcome was unplanned readmission that occurred ≤ 14 days from the date of discharge. Logistic regression models were used to examine variables associated with unplanned readmission for each procedure group. RESULTS: A total of 787,118 patients were included: ventral hernia repair 35.2%, colectomy 30.6%, appendectomy 26.5%, proctectomy 3.7%, small bowel resection 3.2%, and gastrectomy 0.8%. Unplanned reoperation was independently associated with unplanned readmission for ventral hernia repair (OR 2.84, 95% CI 2.28-3.54, P < 0.001), colectomy (OR 1.58, CI 1.42- 1.76, P < 0.001), appendectomy (OR 2.91, CI 2.21-3.84, P < 0.001), and proctectomy (OR 1.41, CI 1.10-1.81, P = 0.006). Other clinically relevant covariates associated with readmission were partially dependent functional status before colectomy (OR 1.34, CI 1.23-1.46, P < 0.001), ventral hernia repair (OR 1.79, CI 1.54-2.09, P < 0.001), and small bowel resection (OR 1.44, CI 1.18-1.77, P < 0.001; and ASA 4/5 classification for colectomy (OR 2.71, CI 2.36-3.11, P < 0.001), proctectomy (OR 2.10, CI 1.48-2.97, P < 0.001), ventral hernia repair (OR 8.19, CI 6.78-9.88, P < 0.001), appendectomy (OR 2.80, CI 2.35-3.34, P < 0.001), and small bowel resection (OR 3.42, CI 2.20-5.32, P < 0.001). ASA 2, ASA 3 classification, age, and sex were also associated with unplanned readmission for most procedures. CONCLUSIONS: Unplanned reoperations are associated with an increase in unplanned readmission after selected abdominal operations included in this study. This factor should be considered in discharge and follow-up planning to help reduce unplanned readmissions.

Development and Impact of an Institutional Enhanced Recovery Program on Opioid Use, Length of Stay, and Hospital Costs Within an Academic Medical Center: A Cohort Analysis of 7774 Patients.

BACKGROUND: Enhanced Recovery (ER) is a change management framework in which a multidisciplinary team of stakeholders utilizes evidence-based medicine to protocolize all aspects of a surgical care to allow more rapid return of function. While service-specific reports of ER adoption are common, institutional-wide adoption is complex, and reports of institution-wide ER adoption are lacking in the United States. We hypothesized that ER principles were generalizable across an institution and could be implemented across a multitude of surgical disciplines with improvements in length of stay, opioid consumption, and cost of care. METHODS: Following the establishment of a formal institutional ER program, ER was adopted in 9 distinct surgical subspecialties over 5 years at an academic medical center. We compared length of stay, opioid consumption, and total cost of care in all surgical subspecialties as a function of time using a segmented regression/interrupted time series statistical model. RESULTS: There were 7774 patients among 9 distinct surgical populations including 2155 patients in the pre-ER cohort and 5619 patients in the post-ER cohort. The introduction of an ER protocol was associated with several significant changes: a reduction in length of stay in 5 of 9 specialties; reduction in opioid consumption in 8 specialties; no change or reduction in maximum patient-reported pain scores; and reduction or no change in hospital costs in all specialties. The ER program was associated with an aggregate increase in profit over the study period. CONCLUSIONS: Institution-wide efforts to adopt ER can generate significant improvements in patient care, opioid consumption, hospital capacity, and profitability within a large academic medical center.

Effect of active versus passive void trials on time to patient discharge, urinary tract infection, and urinary retention: a randomized clinical trial.

PURPOSE: We sought to determine the effect of active versus passive voiding trials on time to hospital discharge and rates of urinary tract infection (UTI) and urinary retention (UR). METHODS: We performed a prospective, randomized trial comparing active (AVT) versus passive (PVT) void trials of inpatients requiring urethral catheter removal. Of 329 eligible patients, 274 were randomized to AVT (bladder filled with saline before catheter removal) or PVT (spontaneous bladder filling after catheter removal). Primary outcome was time to hospital discharge. Secondary outcomes were UTI (NSQIP criteria) and UR (requiring repeat catheterization) within 2 weeks of void trial. RESULTS: The median time to void was 18 (5-115) versus 236 (136-360) min in the AVT and PVT groups, respectively (p < 0.0001). However, no difference was seen in comparison of the median time to hospital discharge between AVT [28.4 (13.6-69.3) h] and PVT [30.0 (10.4-75.6) h] cohorts, respectively (p = 0.93). Six (4.8%) and 13 (12.9%) patients developed UTI in the AVT and PVT groups, respectively (p = 0.03). Eleven (8.8%) and 12 (11.9%) patients developed UR in the AVT and PVT groups, respectively (p = 0.36). CONCLUSION: Our study comparing AVT versus PVT demonstrated no difference in time to discharge despite a 3.6 h reduction in time to void associated with AVT. AVT was associated with a 63% reduction in UTI, with no difference seen in UR rates across cohorts. Given the reduction in UTI and technical advantages, our data suggest that AVT should be considered as a recommended technique for void trial protocol. TRIAL REGISTRATION: NCT02886143 (clinicaltrials.gov).

Comparative Analysis of Established Risk Scores and Novel Hemodynamic Metrics in Predicting Right Ventricular Failure in Left Ventricular Assist Device Patients.

BACKGROUND: Right ventricular failure (RVF) portends poor outcomes after left ventricular assist device (LVAD) implantation. Although numerous RVF predictive models have been developed, there are few independent comparative analyses of these risk models. METHODS AND RESULTS: RVF was defined as use of inotropes for >14 days, inhaled pulmonary vasodilators for >48 hours or unplanned right ventricular mechanical support postoperatively during the index hospitalization. Risk models were evaluated for the primary outcome of RVF by means of logistic regression and receiver operating characteristic curves. Among 93 LVAD patients with complete data from 2011 to 2016, the Michigan RVF score (C = 0.74 [95% CI 0.61-0.87]; P = .0004) was the only risk model to demonstrate significant discrimination for RVF, compared with newer risk scores (Utah, Pitt, EuroMACS). Among individual hemodynamic/echocardiographic metrics, preoperative right ventricular dysfunction (C = 0.72 [95% CI 0.58-0.85]; P = .0022) also demonstrated significant discrimination of RVF. The Michigan RVF score was also the best predictor of in-hospital mortality (C = 0.67 [95% CI 0.52-0.83]; P = .0319) and 3-year survival (Kaplan-Meier log-rank 0.0135). CONCLUSIONS: In external validation analysis, the more established Michigan RVF score-which emphasizes preoperative hemodynamic instability and target end-organ dysfunction-performed best, albeit modestly, in predicting RVF and demonstrated association with in-hospital and long-term mortality.

An Injury Risk Function for the Leg, Foot, and Ankle Exposed to Axial Impact Loading Using Force and Impulse.

Most injury risk functions (IRFs) for dynamic axial loading of the leg have been targeted toward automotive applications such as predicting injury caused by intrusion into the occupant compartment from frontal collisions. Recent focus on leg injuries in the military has led to questions about the applicability of these IRFs shorter duration, higher amplitude loading associated with underbody blast (UBB). To investigate these questions, data were collected from seven separate test series that subjected post-mortem human legs to axial impact. A force and impulse-based Weibull survival model was developed from these studies to estimate fracture risk. Specimen age was included as a covariate to reduce variance and improve survival model fit. The injury criterion estimated 50% risk of injury for a leg exposed to 13 N s of impulse at peak force and 8.07 kN of force for force durations less than and greater than half the natural period of the leg, respectively. A supplemental statistical analysis estimated that the proposed IRF improves injury prediction accuracy by more than 9% compared to the predictions from automobile-based risk functions developed for automotive intrusion. The proposed leg IRF not only improves injury prediction for higher rate conditions but also provides a single injury prediction tool for an expanded range of load durations ranging from 5 to 90 ms, which spans both automotive and military loading environments.

More Frequent Surveillance Following Lung Cancer Resection Is Not Associated With Improved Survival: A Nationally Representative Cohort Study.

OBJECTIVE: To evaluate whether an association exists between the intensity of surveillance following surgical resection for non-small cell lung cancer (NSCLC) and survival. BACKGROUND: Surveillance guidelines following surgical resection of NSCLC vary widely and are based on expert opinion and limited evidence. METHODS: A Special Study of the National Cancer Database randomly selected stage I to III NSCLC patients for data reabstraction. For patients diagnosed between 2006 and 2007 and followed for 5 years through 2012, registrars documented all postsurgical imaging with indication (routine surveillance, new symptoms), recurrence, new primary cancers, and survival, with 5-year follow-up. Patients were placed into surveillance groups according to existing guidelines (3-month, 6-month, annual). Overall survival and survival after recurrence were analyzed using Cox Proportional Hazards Models. RESULTS: A total of 4463 patients were surveilled with computed tomography scans; these patients were grouped based on time from surgery to first surveillance. Groups were similar with respect to age, sex, comorbidities, surgical procedure, and histology. Higher-stage patients received more surveillance. More frequent surveillance was not associated with longer risk-adjusted overall survival [hazard ratio for 6-month: 1.16 (0.99, 1.36) and annual: 1.06 (0.86-1.31) vs 3-month; P value 0.14]. More frequent imaging was also not associated with postrecurrence survival [hazard ratio: 1.02/month since imaging (0.99-1.04); P value 0.43]. CONCLUSIONS: These nationally representative data provide evidence that more frequent postsurgical surveillance is not associated with improved survival. As the number of lung cancer survivors increases over the next decade, surveillance is an increasingly important major health care concern and expenditure.

Acute Kidney Injury in the Age of Enhanced Recovery Protocols.

BACKGROUND: Acute kidney injury is a prevalent complication after abdominal surgery. With increasing adoption of enhanced recovery protocols, concern exists for concomitant increase in acute kidney injury. OBJECTIVE: This study evaluated effects of enhanced recovery on acute kidney injury through identification of risk factors. DESIGN: This was a retrospective cohort study comparing acute kidney injury rates before and after implementation of enhanced recovery protocol. SETTINGS: The study was conducted at a large academic medical center. PATIENTS: All of the patients undergoing elective colorectal surgery between 2010 and 2016, excluding patients with stage 5 chronic kidney disease, were included. MAIN OUTCOME MEASURES: Patients before and after enhanced recovery implementation were compared, with rate of acute kidney injury as the primary outcome. Acute kidney injury was defined as a rise in serum creatinine ≥1.5 times baseline within 30 days of surgery. Multivariable logistic regression identified risk factors for acute kidney injury. RESULTS: A total of 900 cases were identified, including 461 before and 439 after enhanced recovery; 114 cases were complicated by acute kidney injury, including 11.93% of patients before and 13.44% after implementation of enhanced recovery (p = 0.50). Five patients required hemodialysis, with 2 cases after protocol implementation. Multivariable logistic regression identified hypertension, functional status, ureteral stents, nonsteroidal anti-inflammatory drugs, operative time >200 minutes, and increased intravenous fluid administration on postoperative day 1 as predictors of acute kidney injury. Laparoscopic surgery decreased the risk of acute kidney injury. The enhanced recovery protocol was not independently associated with acute kidney injury. LIMITATIONS: The study was limited by its retrospective and nonrandomized before-and-after design. CONCLUSIONS: No difference in rates of acute kidney injury was detected before and after implementation of a colorectal enhanced recovery protocol. Independent predictors of acute kidney injury were identified and could be used to alter the protocol in high-risk patients. Future study is needed to determine whether protocol modifications will further decrease rates of acute kidney injury in this population. See Video Abstract at http://links.lww.com/DCR/A568.

Rear-facing versus forward-facing child restraints: an updated assessment.

OBJECTIVES: The National Highway Traffic Safety Administration and the American Academy of Pediatrics recommend children be placed in rear-facing child restraint systems (RFCRS) until at least age 2. These recommendations are based on laboratory biomechanical tests and field data analyses. Due to concerns raised by an independent researcher, we re-evaluated the field evidence in favour of RFCRS using the National Automotive Sampling System Crashworthiness Data System (NASS-CDS) database. METHODS: Children aged 0 or 1 year old (0-23 months) riding in either rear-facing or forward-facing child restraint systems (FFCRS) were selected from the NASS-CDS database, and injury rates were compared by seat orientation using survey-weighted χ2 tests. In order to compare with previous work, we analysed NASS-CDS years 1988-2003, and then updated the analyses to include all available data using NASS-CDS years 1988-2015. RESULTS: Years 1988-2015 of NASS-CDS contained 1107 children aged 0 or 1 year old meeting inclusion criteria, with 47 of these children sustaining injuries with Injury Severity Score of at least 9. Both 0-year-old and 1-year-old children in RFCRS had lower rates of injury than children in FFCRS, but the available sample size was too small for reasonable statistical power or to allow meaningful regression controlling for covariates. CONCLUSIONS: Non-US field data and laboratory tests support the recommendation that children be kept in RFCRS for as long as possible, but the US NASS-CDS field data are too limited to serve as a strong statistical basis for these recommendations.

Impact of Rotavirus Vaccine Introduction and Postintroduction Etiology of Diarrhea Requiring Hospital Admission in Haydom, Tanzania, a Rural African Setting.

Background: No data are available on the etiology of diarrhea requiring hospitalization after rotavirus vaccine introduction in Africa. The monovalent rotavirus vaccine was introduced in Tanzania on 1 January 2013. We performed a vaccine impact and effectiveness study as well as a quantitative polymerase chain reaction (qPCR)-based etiology study at a rural Tanzanian hospital. Methods: We obtained data on admissions among children <5 years to Haydom Lutheran Hospital between 1 January 2010 and 31 December 2015 and estimated the impact of vaccine introduction on all-cause diarrhea admissions. We then performed a vaccine effectiveness study using the test-negative design. Finally, we tested diarrheal specimens during 2015 by qPCR for a broad range of enteropathogens and calculated pathogen-specific attributable fractions (AFs). Results: Vaccine introduction was associated with a 44.9% (95% confidence interval [CI], 17.6%-97.4%) reduction in diarrhea admissions in 2015, as well as delay of the rotavirus season. The effectiveness of 2 doses of vaccine was 74.8% (95% CI, -8.2% to 94.1%) using an enzyme immunoassay-based case definition and 85.1% (95% CI, 26.5%-97.0%) using a qPCR-based case definition. Among 146 children enrolled in 2015, rotavirus remained the leading etiology of diarrhea requiring hospitalization (AF, 25.8% [95% CI, 24.4%-26.7%]), followed by heat-stable enterotoxin-producing Escherichia coli (AF, 18.4% [95% CI, 12.9%-21.9%]), Shigella/enteroinvasive E. coli (AF, 14.5% [95% CI, 10.2%-22.8%]), and Cryptosporidium (AF, 7.9% [95% CI, 6.2%-9.3%]). Conclusions: Despite the clear impact of vaccine introduction in this setting, rotavirus remained the leading etiology of diarrhea requiring hospitalization. Further efforts to maximize vaccine coverage and improve vaccine performance in these settings are warranted.

Use of quantitative molecular diagnostic methods to identify causes of diarrhoea in children: a reanalysis of the GEMS case-control study.

BACKGROUND: Diarrhoea is the second leading cause of mortality in children worldwide, but establishing the cause can be complicated by diverse diagnostic approaches and varying test characteristics. We used quantitative molecular diagnostic methods to reassess causes of diarrhoea in the Global Enteric Multicenter Study (GEMS). METHODS: GEMS was a study of moderate to severe diarrhoea in children younger than 5 years in Africa and Asia. We used quantitative real-time PCR (qPCR) to test for 32 enteropathogens in stool samples from cases and matched asymptomatic controls from GEMS, and compared pathogen-specific attributable incidences with those found with the original GEMS microbiological methods, including culture, EIA, and reverse-transcriptase PCR. We calculated revised pathogen-specific burdens of disease and assessed causes in individual children. FINDINGS: We analysed 5304 sample pairs. For most pathogens, incidence was greater with qPCR than with the original methods, particularly for adenovirus 40/41 (around five times), Shigella spp or enteroinvasive Escherichia coli (EIEC) and Campylobactor jejuni o C coli (around two times), and heat-stable enterotoxin-producing E coli ([ST-ETEC] around 1·5 times). The six most attributable pathogens became, in descending order, Shigella spp, rotavirus, adenovirus 40/41, ST-ETEC, Cryptosporidium spp, and Campylobacter spp. Pathogen-attributable diarrhoeal burden was 89·3% (95% CI 83·2-96·0) at the population level, compared with 51·5% (48·0-55·0) in the original GEMS analysis. The top six pathogens accounted for 77·8% (74·6-80·9) of all attributable diarrhoea. With use of model-derived quantitative cutoffs to assess individual diarrhoeal cases, 2254 (42·5%) of 5304 cases had one diarrhoea-associated pathogen detected and 2063 (38·9%) had two or more, with Shigella spp and rotavirus being the pathogens most strongly associated with diarrhoea in children with mixed infections. INTERPRETATION: A quantitative molecular diagnostic approach improved population-level and case-level characterisation of the causes of diarrhoea and indicated a high burden of disease associated with six pathogens, for which targeted treatment should be prioritised. FUNDING: Bill & Melinda Gates Foundation.

Management of One-lung Ventilation: Impact of Tidal Volume on Complications after Thoracic Surgery.

BACKGROUND: The use of lung-protective ventilation (LPV) strategies may minimize iatrogenic lung injury in surgical patients. However, the identification of an ideal LPV strategy, particularly during one-lung ventilation (OLV), remains elusive. This study examines the role of ventilator management during OLV and its impact on clinical outcomes. METHODS: Data were retrospectively collected from the hospital electronic medical record and the Society of Thoracic Surgery database for subjects undergoing thoracic surgery with OLV between 2012 and 2014. Mean tidal volume (VT) during two-lung ventilation and OLV and ventilator driving pressure (ΔP) (plateau pressure - positive end-expiratory pressure [PEEP]) were analyzed for the 1,019 cases that met the inclusion criteria. Associations between ventilator parameters and clinical outcomes were examined by multivariate linear regression. RESULTS: After the initiation of OLV, 73.3, 43.3, 18.8, and 7.2% of patients received VT greater than 5, 6, 7, and 8 ml/kg predicted body weight, respectively. One hundred and eighty-four primary and 288 secondary outcome events were recorded. In multivariate logistic regression modeling, VT was inversely related to the incidence of respiratory complications (odds ratio, 0.837; 95% CI, 0.729 to 0.958), while ΔP predicted the development of major morbidity when modeled with VT (odds ratio, 1.034; 95% CI, 1.001 to 1.068). CONCLUSIONS: Low VT per se (i.e., in the absence of sufficient PEEP) has not been unambiguously demonstrated to be beneficial. The authors found that a large proportion of patients continue to receive high VT during OLV and that VT was inversely related to the incidence of respiratory complications and major postoperative morbidity. While low (physiologically appropriate) VT is an important component of an LPV strategy for surgical patients during OLV, current evidence suggests that, without adequate PEEP, low VT does not prevent postoperative respiratory complications. Thus, use of physiologic VT may represent a necessary, but not independently sufficient, component of LPV.

The Effect of Dexmedetomidine on Postoperative Opioid Consumption and Pain After Major Spine Surgery.

BACKGROUND: Adult deformity correction spine surgery can be associated with significant perioperative pain because of inflammatory, muscular, neuropathic, and postsurgical pain. α-2 Agonists have intrinsic antinociceptive and antihyperalgesic properties that can potentially reduce both postoperative opioid consumption and pain. We hypothesized that intraoperative dexmedetomidine would reduce postoperative opioid consumption and improve pain scores in deformity correction spine surgery. METHODS: Patients undergoing >3 levels of thoracic and/or lumbar spine surgery were enrolled in this prospective randomized double-blind study to receive either dexmedetomidine (1 µg/kg load followed by a continuous infusion of 0.5 µg/kg/h) or saline. Both groups received a single dose of 0.2 mg/kg (ideal body weight) of methadone at the start of surgery. Intraoperative fentanyl was administered based on the clinical and hemodynamic signs suggestive of increased nociception. Postoperative analgesia was provided with a hydromorphone patient-controlled analgesia pump. Opioid consumption and pain scores were recorded at 24, 48, and 72 hours after surgery. RESULTS: One hundred forty-two participants were enrolled with 131 completing the study. There was no significant difference in demographics (age, sex, weight, and ASA physical status), percentage of participants with preoperative opioid use, and daily median opioid consumption between the groups. The study was terminated early after interim analysis. Intraoperative opioid use was reduced in the dexmedetomidine arm (placebo versus dexmedetomidine, median [25%-75% interquartile range]: 7 [3-15] vs 3.5 [0-11] mg morphine equivalents, P = 0.04) but not at 24 hours: 49 (30-78) vs 61 (34-77) mg morphine equivalents, P = 0.65, or 48 hours: 41 (28-68) vs 40 (23-64) mg morphine equivalents, P = 0.60, or 72 hours: 29 (15-59) vs 30 (14-46) mg morphine equivalents, P = 0.58. The Wilcoxon-Mann-Whitney odds are 1.11 with 97.06% confidence interval (0.71-1.76) for opioid consumption. No difference in pain score, as measured by the 11-point visual analog scale, was seen at 24 hours (placebo versus dexmedetomidine, median [25%-75% interquartile range]: 7 [5-7] vs 6 [4-7], P = 0.12) and 48 hours (5 [3-7] vs 5 [3-6], P = 0.65). There was an increased incidence of bradycardia (placebo: 37% vs dexmedetomidine: 59% P = 0.02) and phenylephrine use in the dexmedetomidine group (placebo: 59% versus dexmedetomidine: 78%, P = 0.03). CONCLUSIONS: Intraoperative dexmedetomidine does not reduce postoperative opioid consumption or improve pain scores after multilevel deformity correction spine surgery.

Mobile Telestroke During Ambulance Transport Is Feasible in a Rural EMS Setting: The iTREAT Study.

BACKGROUND: The use of telemedicine in the diagnosis and treatment of acute stroke, or telestroke, is a well-accepted method of practice improving geographic disparities in timely access to neurological expertise. We propose that mobile telestroke assessment during ambulance transport is feasible using low-cost, widely available technology. MATERIALS AND METHODS: We designed a platform including a tablet-based end point, high-speed modem with commercial wireless access, external antennae, and portable mounting apparatus. Mobile connectivity testing was performed along six primary ambulance routes in a rural network. Audiovisual (AV) quality was assessed simultaneously by both an in-vehicle and an in-hospital rater using a standardized 6-point rating scale (≥4 indicating feasibility). We sought to achieve 9 min of continuous AV connectivity presumed sufficient to perform mobile telestroke assessments. RESULTS: Thirty test runs were completed: 93% achieved a minimum of 9 min of continuous video transmission with a mean mobile connectivity time of 18 min. Mean video and audio quality ratings were 4.51 (4.54 vehicle; 4.48 hospital) and 5.00 (5.13 in-vehicle; 4.87 hospital), respectively. Total initial cost of the system was $1,650 per ambulance. CONCLUSIONS: In this small, single-centered study we maintained high-quality continuous video transmission along primary ambulance corridors using a low-cost mobile telemedicine platform. The system is designed to be portable and adaptable, with generalizability for rapid assessment of emergency conditions in which direct observational exam may improve prehospital diagnosis and treatment. Thus mobile telestroke assessment is feasible using low-cost components and commercial wireless connectivity. More research is needed to demonstrate clinical reliability and efficacy in a live-patient setting.