Daniel K. Benjamin | Clemson University (original) (raw)

Papers by Daniel K. Benjamin

The Journal of Economic History, 2007

Between 1660 and 1815 the combat fatality rate among British navy captains fell by 98 percent, ev... more Between 1660 and 1815 the combat fatality rate among British navy captains fell by 98 percent, even as the combat success of the British Navy rose dramatically. Both developments can be explained as a result of learning by doing among British commanders. This learning was importantly driven by the extensive wartime experience accumulated over this period, combined with the unparalleled financial incentives for combat success offered to British commanders.

Early human development, Jan 3, 2018

At very high doses, furosemide is linked to ototoxicity in adults, but little is known about the ... more At very high doses, furosemide is linked to ototoxicity in adults, but little is known about the risk of hearing loss in premature infants exposed to furosemide. Evaluate the association between prolonged furosemide exposure and abnormal hearing screening in premature infants. Using propensity scoring, infants with prolonged (≥28 days) exposure to furosemide were matched to infants never exposed. The matched sample was used to estimate the impact of prolonged furosemide exposure on the probability of an abnormal hearing screen prior to hospital discharge. A cohort of infants 501-1250 g birth weight and 23-29 weeks gestational age discharged home from 210 neonatal intensive care units in the United States (2004-2013). We defined abnormal hearing screen as a result of either "fail" or "refer" for either ear. Altogether, 1020 infants exposed to furosemide for ≥28 days were matched to 790 unique infants never exposed, yielding a total of 1042 matches due to sampling ...

The Journal of pediatrics, Jan 14, 2018

To estimate the relationship of initial pharmacotherapy with methadone or morphine and length of ... more To estimate the relationship of initial pharmacotherapy with methadone or morphine and length of stay (LOS) in infants with neonatal abstinence syndrome (NAS) admitted to the neonatal intensive care unit (NICU). From the Pediatrix Clinical Data Warehouse database, we identified all infants born at ≥36 weeks of gestation between 2011 and 2015 who were diagnosed with NAS (International Classification of Diseases, Ninth Revision code 779.5) and treated with methadone or morphine in the first 7 days of life. We used multivariable Cox proportional hazards regression analysis to quantify the association between initial treatment and LOS after adjusting for maternal age, maternal race/ethnicity, maternal drug use, maternal smoking, gestational age, small for gestational age status, inborn status, and discharge year. We identified a total of 7667 eligible infants, including 1187 treated with methadone (15%) and 6480 treated with morphine (85%). Birth weight, gestational age, and sex were si...

The Journal of pediatrics, Jan 21, 2018

To characterize the association between gentamicin dosing, duration of treatment, and ototoxicity... more To characterize the association between gentamicin dosing, duration of treatment, and ototoxicity in hospitalized infants. This retrospective cohort study conducted at 330 neonatal intensive care units (2002-2014) included inborn infants exposed to gentamicin with available hearing screen results, and excluded infants with incomplete dosing data and major congenital anomalies. Our primary outcome was the final hearing screen result performed during hospitalization: abnormal (failed or referred for further testing in one or both ears) or normal (bilateral passed). The 4 measures of gentamicin exposure were highest daily dose, average daily dose, cumulative dose, and cumulative duration of exposure. We fitted separate multivariable logistic regression models adjusted for demographics, comorbidities, and other clinical events. A total of 84 808 infants met inclusion/exclusion criteria; median (25th, 75th percentile) gestational age and birth weight were 35 weeks (33, 38) and 2480 g (18...

The Journal of pediatrics, Jan 29, 2018

To evaluate the association between the presence of an atrial septal defect (ASD) and the odds of... more To evaluate the association between the presence of an atrial septal defect (ASD) and the odds of developing bronchopulmonary dysplasia (BPD) in premature infants. We identified a cohort of infants that underwent at least one echocardiogram assessment, birth weight 501-1249 g, and gestational age 23-30 weeks discharged from the neonatal intensive care unit from 2004 to 2016. We used a BPD risk estimator to calculate the predicted risk of developing BPD at 6 postnatal ages within the first 28 days of life. We examined the association between the presence of an ASD and the development of BPD using 2 multivariable logistic regression models for each BPD risk severity on each postnatal day. The first model adjusted for predicted BPD risk and the second added therapeutic interventions for BPD. Of 20 496 infants from 228 NICUs who met inclusion criteria, 8892 (43%) were diagnosed with BPD and 1314 (6%) had an ASD. BPD was present in 48% of infants with an ASD and 43% of infants without an...

The Journal of Pediatrics

Objective-To test the hypothesis that early caffeine treatment on the day of birth, compared with... more Objective-To test the hypothesis that early caffeine treatment on the day of birth, compared with later treatment in very low birth weight (VLBW, <1500 g) infants receiving continuous positive airway pressure (CPAP) therapy, is associated with a decreased risk of CPAP failure in the first week of life. Study design-Multicenter, observational cohort study in 366 US neonatal intensive care units. We evaluated inborn, VLBW infants discharged from 2000 to 2014, who received only CPAP therapy without surfactant treatment on day of life (DOL) 0, had a 5-minute Apgar ≥3, and received caffeine in first week of life. We used multivariable conditional logistic regression to compare the risk of CPAP failure, defined as invasive mechanical ventilation or surfactant therapy on DOL 1-6, by timing of caffeine treatment as either early (initiation on DOL 0) or routine (initiation on DOL 1-6). Results-We identified 11 133 infants; 4528 (41%) received early caffeine and 6605 (59%) received routine caffeine. Median gestational age was lower in the early caffeine group, 29 weeks (25th, 75th percentiles; 28, 30) vs the routine caffeine group, 30 weeks (29, 31); P < 0.001. The incidence of CPAP failure on DOL 1-6 was similar between the early and routine caffeine groups: 22% vs 21%; adjusted OR = 1.05 (95% CI: 0.93, 1.18). Conclusions-Early caffeine treatment on the day of birth was not associated with a decreased risk of CPAP failure in the first week of life for VLBW infants initially treated with CPAP.

Pediatric nephrology (Berlin, Germany), Jan 4, 2017

Hypertension and chronic kidney disease (CKD) are common comorbidities. Guidelines recommend trea... more Hypertension and chronic kidney disease (CKD) are common comorbidities. Guidelines recommend treating hypertension in children with CKD because it is a modifiable risk factor for subsequent cardiovascular disease. Children with CKD are frequently excluded from antihypertensive drug trials. Consequently, safety and efficacy data for antihypertensive drugs are lacking in children with CKD. We determined the incidence of adverse events in 10 pediatric antihypertensive trials to determine the effect of renal function on antihypertensive safety and efficacy in children. These trials were submitted to the US Food and Drug Administration from 1998 to 2005. We determined the number and type of adverse events reported during the trials and compared these numbers in participants with normal renal function and those with decreased function (defined as an estimated glomerular filtration rate [eGFR] <90 mL/min/1.73 m(2) calculated using the original Schwartz equation). Among the 1,703 childre...

The Journal of pediatrics, Apr 18, 2017

To assess how neonatal intensive care units followed the American Academy of Pediatrics guideline... more To assess how neonatal intensive care units followed the American Academy of Pediatrics guidelines for use of dexamethasone in preterm infants by evaluating respiratory support at the time of dexamethasone administration. This is an observational study of infants discharged from one of 290 neonatal intensive care units from 2003 to 2010. The cohort included very low birth weight (<1500 g birth weight) infants born at ≤32 weeks gestational age. The main outcome was respiratory support at time of exposure to dexamethasone. Significant respiratory support was defined as invasive respiratory support (conventional or high-frequency ventilation) with a fraction of inspired oxygen (FiO2) > 0.3. Of 81 292 infants; 7093 (9%) received dexamethasone. At the time that dexamethasone was initiated, 4604 (65%) of infants were on significant respiratory support. In accordance with the American Academy of Pediatrics recommendations, a majority of infants were on significant respiratory support...

Pediatric cardiology, Jan 8, 2016

Enalapril is used to treat hypertension and congestive heart failure in infants. However, enalapr... more Enalapril is used to treat hypertension and congestive heart failure in infants. However, enalapril is not labeled for neonates, and safety data in infants are sparse. To evaluate the safety of enalapril in young infants, we conducted a retrospective cohort study of infants who were exposed to enalapril in the first 120 days of life and were cared for in 348 neonatal intensive care units from 1997 to 2012. We determined the proportion of exposed infants who developed adverse events, including death, hypotension requiring pressors, hyperkalemia, and elevated serum creatinine. Using multivariable logistic regression, we examined risk factors for adverse events, including postnatal age at first exposure, exposure duration, gestational age group, small for gestational age status, race, sex, 5-min Apgar score, and inborn status. Of a cohort of 887,910 infants, 662 infants (0.07%) were exposed to enalapril. Among exposed infants, 142 infants (21%) suffered an adverse event. The most commo...

American Journal of Perinatology, 2016

Objective-Identify the progression of specific signs of multi-organ dysfunction among infants wit... more Objective-Identify the progression of specific signs of multi-organ dysfunction among infants with fatal sepsis. Study design-Cohort study of 679 infants who died within 3 days of the start of a late-onset sepsis (LOS) episode in neonatal intensive care units from 1997-2012. We extracted clinical and laboratory data on the day of death (day 0) and the preceding 5 days (days −5 to −1). Results-Median (25 th percentile-75 th percentile) gestational age was 25 (24-28) weeks. Compared with day −1, day 0 was characterized by an increased requirement for mechanical ventilation and higher mean fraction of inspired oxygen. Measures of cardiorespiratory support and the proportion of infants with neutropenia began to rise on day −2. Conclusions-Hospitalized infants with fatal LOS manifest respiratory, cardiovascular, renal, immune, and hematologic dysfunction. Knowledge of these factors and their timing may be important for the development and testing of novel therapeutics to reduce sepsis mortality.

The Journal of pediatrics, Jan 10, 2016

To characterize administration of sedatives, analgesics, and paralytics in a large cohort of mech... more To characterize administration of sedatives, analgesics, and paralytics in a large cohort of mechanically ventilated premature infants. Retrospective cohort study including all infants <1500 g birth weight and <32 weeks gestational age (GA) mechanically ventilated at 348 Pediatrix Medical Group neonatal intensive care units from 1997 to 2012. The primary outcome is the proportion of mechanically ventilated days in which infants were administered drugs of interest. Multivariable logistic regression was used to evaluate the predictors of administration of drugs of interest. We identified 85 911 mechanically ventilated infants. Infants received a drug of interest (opioids, benzodiazepines, other sedatives, and paralytics) on 433 587/1 305 413 (33%) of mechanically ventilated infant days. The administration of opioids increased during the study period from 5% of infant days in 1997 to 32% in 2012. The administration of benzodiazepines increased during the study period from 5% of i...

Clinical pediatrics, Jan 21, 2016

Urinary tract infections (UTIs) are a source of substantial morbidity in children in the neonatal... more Urinary tract infections (UTIs) are a source of substantial morbidity in children in the neonatal intensive care unit. The incidence of UTIs that occur in critically ill infants during a course of antibiotic prophylaxis (i.e., breakthrough urinary tract infections [BUTIs]) is not known. We investigated the incidence of BUTI in a cohort of infants hospitalized on prophylactic antibiotics in neonatal intensive care units. Predictors of BUTI were evaluated using multivariable Cox regression. Out of 716 787 infants, 631 (0.09%) were prescribed 821 courses of antibiotic prophylaxis. Among this cohort, 60 infants (9.5%) suffered a total of 65 BUTIs. Of all prophylactic antibiotic courses, 65/821 (7.9%) were complicated by BUTI.Klebsiella, Enterobacter, andEscherichia colispecies were the most common causes of BUTI. There was no statistically significant difference (P= .78) in BUTI incidence among the 4 antibiotics assessed (amoxicillin, cephalexin, nitrofurantoin, or trimethoprim-sulfamet...

JAMA pediatrics, Jan 7, 2015

Postnatally acquired cytomegalovirus (CMV) is typically benign in term infants but in very low-bi... more Postnatally acquired cytomegalovirus (CMV) is typically benign in term infants but in very low-birth-weight (VLBW) infants can cause pneumonitis and sepsislike illness. Whether postnatal CMV infection results in long-term pulmonary sequelae in these infants is unknown. To investigate the association between postnatal CMV infection and bronchopulmonary dysplasia (BPD) and mortality in a large multicenter cohort of VLBW infants. Conducted between October 2014 and June 2015, this propensity-matched retrospective cohort study involved 101 111 hospitalized VLBW (<1500 g) infants at 348 neonatal intensive care units in the United States from 1997 to 2012. We matched infants with postnatal CMV infection 1:1 to comparison infants using propensity scores, and we used Poisson regression to examine the effect of postnatal CMV on the combined risk for death or BPD at 36 weeks' postmenstrual age. To describe features of postnatal CMV infection, we extracted clinical and laboratory data fr...

JAMA Pediatrics, 2015

IMPORTANCE Staphylococcus aureus is a frequent cause of infection in hospitalized infants. These ... more IMPORTANCE Staphylococcus aureus is a frequent cause of infection in hospitalized infants. These infections are associated with increased mortality and morbidity and longer hospital stays, but data on the burden of S aureus disease in hospitalized infants are limited. OBJECTIVES To compare demographics and mortality of infants with invasive methicillin-resistant S aureus (MRSA) and methicillin-susceptible S aureus (MSSA), to determine the annual proportion of S aureus infections that were MRSA, and to contrast the risk of death after an invasive MRSA infection with the risk after an invasive MSSA infection. DESIGN, SETTING, AND PARTICIPANTS Multicenter retrospective study of a large, nationally representative cohort at 348 neonatal intensive care units managed by the Pediatrix Medical Group. Participants were 3888 infants with an invasive S aureus infection who were discharged from calendar year 1997 through calendar year 2012. EXPOSURE Invasive S aureus infection. MAIN OUTCOMES AND MEASURES The incidence of invasive S aureus infections, as well as infant characteristics and mortality after MRSA or MSSA infection. RESULTS The 3888 infants had 3978 invasive S aureus infections (2868 MSSA and 1110 MRSA). The incidence of invasive S aureus infection was 44.8 infections per 10 000 infants. The yearly proportion of invasive infections caused by MRSA increased from calendar year 1997 through calendar year 2006 and has moderately decreased since then. Infants with invasive MRSA or MSSA infections had similar gestational ages and birth weights. Invasive MRSA infections occurred more often at a younger postnatal age. For infants with available mortality data, more infants with invasive MSSA infections (n = 237) died before hospital discharge than infants with invasive MRSA infections (n = 110). The proportions of infants who died after invasive MSSA and MRSA infections were similar at 237 of 2474 (9.6%) and 110 of 926 (11.9%), respectively (P = .05). The adjusted risk of death before hospital discharge was similar after invasive MSSA and MRSA infections (risk ratio, 1.19; 95% CI, 0.96-1.49). The risks of death at 7 and 30 days after invasive infection were similar between infants with invasive MSSA infection and infants with invasive MRSA infection. CONCLUSIONS AND RELEVANCE Infant mortality after invasive MRSA and MSSA infections is similar, but MSSA causes more infections and more deaths in infants than MRSA. Measures to prevent S aureus infection should include MSSA in addition to MRSA.

It is widely argued that individuals have biased perceptions of health and safety risks. A recons... more It is widely argued that individuals have biased perceptions of health and safety risks. A reconsideration of the best-known evidence suggests that this view is the erroneous result of a failure to consider the implications of scarce information. Our findings imply that the hypothesis that people make unbiased estimates of hazard rates fails to be rejected by the very data that were initially used to reject it. Thus, we are able to reconcile the alleged existence of widespread bias in risk perception with other findings that such bias is less apparent in the case of job-related hazards. The seeming bias in estimating population-average death rates and the lack of such bias in assessing job risks are two manifestations of the same behavior, which is the optimal acquisition of costly information.

Pediatrics, 2015

To evaluate the effect of anaerobic antimicrobial therapy for necrotizing enterocolitis (NEC) on ... more To evaluate the effect of anaerobic antimicrobial therapy for necrotizing enterocolitis (NEC) on clinical outcomes in very low birth weight (≤1500 g) infants. We identified very low birth weight infants with NEC from 348 US NICUs from 1997 to 2012. Anaerobic antimicrobial therapy was defined by antibiotic exposure on the first day of NEC. We matched (1:1) infants exposed to anaerobic antimicrobial therapy with infants who were not exposed by using a propensity score stratified by NEC severity (medical and surgical). The primary composite outcome was in-hospital death or intestinal stricture. We assessed the relationship between anaerobic antimicrobial therapy and outcome by using a conditional logistic regression on the matched cohort. A total of 1390 infants exposed to anaerobic antimicrobial therapy were matched with 1390 infants not exposed. Mean gestational age and birth weight were 27 weeks and 946 g, respectively, and were similar in both groups. We found no significant differ...

The Journal of Law and Economics, 1997

We develop a model in which optimizing policy makers in adjacent government jurisdictions levy ex... more We develop a model in which optimizing policy makers in adjacent government jurisdictions levy excise taxes on a commodity that has a unique point of production from which all shipments emanate. From this model we derive an unusually specific predicted geographical pattern ...

The Journal of Law and Economics, 1974

PEDIATRICS, 2001

Objectives. Physicians who treat neonates who become bacteremic while dependent on central venous... more Objectives. Physicians who treat neonates who become bacteremic while dependent on central venous catheters face a serious and common dilemma. We sought 1) to evaluate the relationship between central venous catheter removal and outcome in bacteremic neonates, 2) to determine species of bacteria that are associated with an increased risk of infectious complications if the central catheter is not removed promptly, and 3) to provide evidence-based recommendations for central catheter management. Method. A retrospective cohort study of all neonates who had central venous access and developed bacteremia between July 1, 1995, and July 31, 1999, was conducted in the Duke University neonatal intensive care unit. Results. The outcome for patients in whom the central catheter was not removed within 24 hours of organism identification was significantly worse (odds ratio = 9.8) than it was for those whose catheters were removed promptly. For patients who were infected withStaphylococcus aureus...