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1.  “Optic neuritis” that is neither 
Neurology: Clinical Practice  2013;3(2):168-170.
A 28-year-old African American woman developed periocular pain worsening with eye movement and decreased vision in her left eye. A diagnosis of left optic neuropathy was made based on the findings of decreased vision in the left eye, a left relative afferent pupillary defect, and mild optic disc hyperemia in the left eye (figure 1), with normal retinae and maculae bilaterally. Automated perimetry showed a small central scotoma in the left eye. The pain with eye movements suggested an inflammatory mechanism (i.e., optic neuritis). Her neurologic examination was normal. MRI of the brain showed 2 small T2 hyperintense lesions in the right inferior frontal lobe and left periatrial white matter. The lesions did not enhance. Angiotensin converting enzyme level was slightly elevated. A chest CT was negative for pulmonary sarcoidosis. She did not receive steroids, and her visual function improved spontaneously over a few weeks. She had no neurologic symptoms and the diagnosis of clinically isolated syndrome was made. The patient declined treatment with an immunomodulatory agent.
PMCID: PMC3721238  PMID: 23914325
2.  Non-mydriatic ocular fundus photography and telemedicine: past, present, and future 
Neuro-ophthalmology (Aeolus Press)  2013;37(2):10.3109/01658107.2013.773451.
Non-mydriatic ocular fundus photography is a promising alternative to direct ophthalmoscopy, particularly when combined with telemedicine. This review discusses these technologies from a longitudinal perspective: past, present, and future. The focus is directed to the role that non-mydriatic fundus photography and telemedicine have played in medical research and patient care, with emphasis on the major advances to date. Also discussed are the challenges to their widespread application and their substantial promise for revitalizing the importance of the ocular fundus examination in patient care, providing improved access to ophthalmic consultative services, and facilitating clinical and epidemiologic research.
PMCID: PMC3826661  PMID: 24244059
Fundus photography; telemedicine; review; ophthalmology; neurology
3.  Idiopathic Intracranial Hypertension: Relation Between Obesity and Visual Outcomes 
Increased body mass index (BMI) has been associated with increased risk of idiopathic intracranial hypertension (IIH), but the relationship of BMI to visual outcomes in IIH is unclear.
A retrospective chart review of all adult cases of IIH satisfying the modified Dandy criteria seen at our institution between 1989 and 2010 was performed. Demographics, diagnostic evaluations, baseline visit and last follow-up examination data, treatment and visual outcome data were collected in a standardized fashion. Groups were compared and logistic regression was used to evaluate the relationship of BMI to severe visual loss, evaluating for interaction and controlling for potential confounders.
Among 414 consecutive IIH patients, 158 had BMI≥40 (WHO Obese Class III), and 172 had BMI 30–39.9. Patients with BMI≥40 were more likely to have severe papilledema at first neuro-ophthalmology encounter than those with a lower BMI (p=0.02). There was a trend toward more severe visual loss in one or both eyes at last follow up among those patients with BMI≥40 (18 vs. 11%, p=0.067). Logistic regression modelling found that ten unit (kg/m2) increases in BMI increased the odds of severe visual loss by 1.4 times (95%CI: 1.03–1.91, p=0.03), after controlling for sex, race, diagnosed hypertension, and diagnosed sleep apnea.
Our finding of a trend for severe papilledema and visual loss associated with increasing BMI suggests that very obese IIH patients should be closely monitored for progression of visual field loss.
PMCID: PMC3323689  PMID: 22217456
Idiopathic Intracranial Hypertension; Body Mass Index; Obesity; Visual Outcomes; Severe Vision Loss; Risk Factors
4.  MRI findings of elevated intracranial pressure in cerebral venous thrombosis versus idiopathic intracranial hypertension with transverse sinus stenosis 
To determine whether MRI signs suggesting elevated intracranial pressure (ICP) are preferentially found in patients with idiopathic intracranial hypertension (IIH) than in those with cerebral venous thrombosis (CVT).
Among 240 patients who underwent standardized contrast-enhanced brain MRI/MRV at our institution between 9/2009 and 9/2011, 60 with abnormal imaging findings on MRV were included: 27 patients with definite IIH, 2 patients with presumed IIH, and 31 with definite CVT. Medical records were reviewed, and imaging studies were prospectively evaluated by the same neuroradiologist to assess for presence or absence of transverse sinus stenosis (TSS), site of CVT if present, posterior globe flattening, optic nerve sheath dilation/tortuosity, and the size/appearance of the sella turcica.
29 IIH patients (28 women, 19 black, median-age 28, median-body mass index, 34) had bilateral TSS. 31 CVT patients (19 women, 13 black, median-age 46, median-BMI 29) had thrombosis of the sagittal (3), sigmoid (3), cavernous (1), unilateral transverse (7), or multiple (16) sinuses or cortical veins (1). Empty/partially-empty sellae were more common in IIH (3/29 and 24/29) than in CVT patients (1/31 and 19/31) (p<0.001). Flattening of the globes and dilation/tortuosity of the optic nerve sheaths were more common in IIH (20/29 and 18/29) than in CVT patients (13/31 and 5/31) (p<0.04).
Although abnormal imaging findings suggestive of raised ICP are more common in IIH, they are not specific for IIH and are found in patients with raised ICP from other causes such as CVT.
PMCID: PMC3765015  PMID: 24019557
idiopathic intracranial hypertension; cerebral venous thrombosis; venous hypertension; MRI; MRV; empty sella
5.  Nonmydriatic ocular fundus photography among headache patients in an emergency department 
Neurology  2013;80(5):432-437.
Determine the frequency of and the predictive factors for abnormal ocular fundus findings among emergency department (ED) headache patients.
Cross-sectional study of prospectively enrolled adult patients presenting to our ED with a chief complaint of headache. Ocular fundus photographs were obtained using a nonmydriatic fundus camera that does not require pupillary dilation. Demographic and neuroimaging information was collected. Photographs were reviewed independently by 2 neuroophthalmologists for findings relevant to acute care. The results were analyzed using univariate statistics and logistic regression modeling.
We included 497 patients (median age: 40 years, 73% women), among whom 42 (8.5%, 95% confidence interval: 6%–11%) had ocular fundus abnormalities. Of these 42 patients, 12 had disc edema, 9 had optic nerve pallor, 6 had grade III/IV hypertensive retinopathy, and 15 had isolated retinal hemorrhages. Body mass index ≥35 kg/m2 (odds ratio [OR]: 2.3, p = 0.02), younger age (OR: 0.7 per 10-year increase, p = 0.02), and higher mean arterial blood pressure (OR: 1.3 per 10-mm Hg increase, p = 0.003) were predictive of abnormal retinal photography. Patients with an abnormal fundus had a higher percentage of hospital admission (21% vs 10%, p = 0.04). Among the 34 patients with abnormal ocular fundi who had brain imaging, 14 (41%) had normal imaging.
Ocular fundus abnormalities were found in 8.5% of patients with headache presenting to our ED. Predictors of abnormal funduscopic findings included higher body mass index, younger age, and higher blood pressure. Our study confirms the importance of funduscopic examination in patients with headache, particularly in the ED, and reaffirms the utility of nonmydriatic fundus photography in this setting.
PMCID: PMC3590046  PMID: 23284060
6.  Clinical course of idiopathic intracranial hypertension with transverse sinus stenosis 
Neurology  2013;80(3):289-295.
Transverse sinus stenosis (TSS) is common in idiopathic intracranial hypertension (IIH), but its effect on the course and outcome of IIH is unknown. We evaluated differences in TSS characteristics between patients with IIH with “good” vs “poor” clinical courses.
All patients with IIH seen in our institution after September 2009 who underwent a high-quality standardized brain magnetic resonance venogram (MRV) were included. Patients were categorized as having a good or poor clinical course based on medical record review. The location and percent of each TSS were determined for each patient, and were correlated to the clinical outcome.
We included 51 patients. Forty-six patients had bilateral TSS. The median average percent stenosis was 56%. Seventy-one percent of patients had stenoses >50%. Thirty-five of the 51 patients (69%) had no final visual field loss. Eight patients (16%) had a clinical course classified as poor. There was no difference in the average percent stenosis between those with good clinical courses vs those with poor courses (62% vs 56%, p = 0.44). There was no difference in the percent stenosis based on the visual field grade (p = 0.38). CSF opening pressure was not associated with either location or degree of TSS.
TSS is common, if not universal, among patients with IIH, and is almost always bilateral. There is no correlation between the degree of TSS and the clinical course, including visual field loss, among patients with IIH, suggesting that clinical features, not the degree of TSS, should be used to determine management in IIH.
PMCID: PMC3589184  PMID: 23269597
7.  Outcome of Extremely Low Birth Weight Infants with Congenital Heart Defects in the Eunice Kennedy Shriver NICHD Neonatal Research Network 
Pediatric cardiology  2012;33(8):1415-1426.
Little is known about the outcomes of extremely low birth weight (ELBW) preterm infants with congenital heart defects (CHDs). The aim of this study was to assess the mortality, morbidity, and early childhood outcomes of ELBW infants with isolated CHD compared with infants with no congenital defects. Participants were 401–1,000 g infants cared for at National Institute of Child Health and Human Development Neonatal Research Network centers between January 1, 1998 and December 31, 2005. Neonatal morbidities and 18–22 months’ corrected age outcomes were assessed. Neurodevelopmental impairment (NDI) was defined as moderate to severe cerebral palsy, Bayley II mental or psychomotor developmental index < 70, bilateral blindness, or hearing impairment requiring aids. Poisson regression models were used to estimate relative risks for outcomes while adjusting for gestational age, small for gestational-age status, and other variables. Of 14,457 ELBW infants, 110 (0.8 %) had isolated CHD, and 13,887 (96 %) had no major birth defect. The most common CHD were septal defects, tetralogy of Fallot, pulmonary valve stenosis, and coarctation of the aorta. Infants with CHD experienced increased mortality (48 % compared with 35 % for infants with no birth defect) and poorer growth. Surprisingly, the adjusted risks of other short-term neonatal morbidities associated with prematurity were not significantly different. Fifty-seven (52 %) infants with CHD survived to 18–22 months’ corrected age, and 49 (86 %) infants completed follow-up. A higher proportion of surviving infants with CHD were impaired compared with those without birth defects (57 vs. 38 %, p = 0.004). Risk of death or NDI was greater for ELBW infants with CHD, although 20% of infants survived without NDI.
PMCID: PMC3687358  PMID: 22644414
heart defects; congenital; follow-up studies
8.  The use of retinal photography in non-ophthalmic settings and its potential for neurology 
The neurologist  2012;18(6):350-355.
Ocular fundus examination is an important element of the neurological examination. However, direct ophthalmoscopy is difficult to perform without pupillary dilation and requires extensive practice to accurately recognize optic nerve and retinal abnormalities. Recent studies have suggested that digital retinal photography can replace direct ophthalmoscopy in many settings.
Review Summary
Ocular fundus imaging is routinely used to document and monitor disease progression in ophthalmology. Advances in optical technology have made it easier to obtain high-quality retinal imaging, even without pupillary dilation. Retinal photography has a high sensitivity, specificity, and inter-/intra-examination agreement compared to in-person ophthalmologist examination, suggesting that photographs can be used in lieu of ophthalmoscopy in many clinical situations. Non-mydriatic retinal photography has recently gained relevance as a helpful tool for diagnosing neuro-ophthalmologic disorders in the emergency department. Additionally, several population-based studies have used retinal imaging to relate ophthalmic abnormalities to the risk of hypertension, renal dysfunction, cardiovascular mortality, subclinical and clinical stroke, and cognitive impairment. The possibility of telemedical consultation offered by digital retinal photography has already increased access to timely and accurate subspecialty care, particularly for underserved areas.
Retinal photography (even without pupillary dilation) has become increasingly available to medical fields outside of ophthalmology, allowing for faster and more accurate diagnosis of various ocular, neurologic and systemic disorders. The potential for telemedicine may provide the additional benefits of improving access to appropriate urgent consultation in both clinical and research settings.
PMCID: PMC3521530  PMID: 23114666
direct ophthalmoscopy; retinal photography; fundus camera; telemedicine
9.  Exacerbation of Susac Syndrome Retinopathy by Interferon Beta-1a 
Archives of ophthalmology  2012;130(6):10.1001/archophthalmol.2011.1841.
PMCID: PMC3809003  PMID: 22801853
10.  Choroidal Infarction in Fulminant Idiopathic Intracranial Hypertension 
PMCID: PMC3721341  PMID: 20404747
Choroid; Infarction; Papilledema; Intracranial Hypertension
11.  Treatment of Nonarteritic Anterior Ischemic Optic Neuropathy 
Survey of ophthalmology  2010;55(1):47-63.
Nonarteritic anterior ischemic optic neuropathy (NAION) is the most common clinical presentation of acute ischemic damage to the optic nerve. Most treatments proposed for NAION are empirical and include a wide range of agents presumed to act on thrombosis, on the blood vessels, or on the disc edema itself. Others are presumed to have a neuroprotective effect. Although there have been multiple therapies attempted, most have not been adequately studied, and animal models of NAION have only recently emerged. The Ischemic Optic Neuropathy Decompression Trial (IONDT), the only class I large multicenter prospective treatment trial for NAION, found no benefit from surgical intervention. One recent large, nonrandomized controlled study suggested that oral steroids might be helpful for acute NAION. Others recently proposed interventions are intravitreal injections of steroids or anti-vascular endothelial growth factor (anti-VEGF) agents. There are no class I studies showing benefit from either medical or surgical treatments. Most of the literature on the treatment of NAION consists of retrospective or prospective case series and anecdotal case reports. Similarly, therapies aimed at secondary prevention of fellow eye involvement in NAION remain of unproven benefit.
PMCID: PMC3721361  PMID: 20006051
nonarteritic anterior ischemic optic neuropathy; treatment; pathogenesis; Ischemic Optic Neuropathy Decompression Trial (IONDT)
12.  Feasibility Study of Early Blood Pressure Management in Extremely Preterm Infants 
The Journal of Pediatrics  2012;161(1):65-69.e1.
To assess the feasibility of a randomized placebo controlled trial (RCT) of blood pressure (BP) management for extremely preterm infants.
Study design
This was a prospective pilot RCT of infants 230/7 – 266/7 weeks gestation who had protocol-defined low BP in the first 24 postnatal hours. Enrolled infants were administered a study infusion (dopamine or placebo) and a study syringe medication (hydrocortisone or placebo).
Of the 366 infants screened, 119 (33%) had low BP, 58 (16%) met all entry criteria, and 10 (3%) were enrolled. 161 (44%) infants were ineligible because they received early indomethacin. Only 17% of eligible infants were enrolled. Problems with consent included insufficient time, parent unavailability, and physician unwillingness to enroll critically ill infants. Two infants were withdrawn from the study due to the potential risk of intestinal perforation with simultaneous administration of hydrocortisone and indomethacin.
This pilot RCT was not feasible due to low eligibility and consent rates. An RCT of BP management for extremely preterm infants may require a waiver of consent for research in emergency care. The frequent use of early indomethacin and the associated risk of intestinal perforation when used with hydrocortisone may limit future investigations to only inotropic medications.
PMCID: PMC3357442  PMID: 22336574
Extremely preterm infant; hypotension; hydrocortisone; dopamine; informed consent
14.  Outcomes of Extremely Low Birth Weight Infants with Bronchopulmonary Dysplasia: Impact of the Physiologic Definition 
Early human development  2012;88(7):509-515.
We compared neurodevelopmental outcomes of extremely low birth weight (ELBW) infants with and without bronchopulmonary dysplasia (BPD), using the physiologic definition.
Study Design
ELBW (birth weights <1000 grams) infants admitted to the Neonatal Research Network centers and hospitalized at 36 weeks postmenstrual age (n=1,189) were classified using the physiologic definition of BPD. Infants underwent Bayley III assessment at 18-22 months corrected age. Multivariable logistic regression was used to determine the association between physiologic BPD and cognitive impairment (score < 70).
BPD by the physiologic definition was diagnosed in 603 (52%) infants, 537 of whom were mechanically ventilated or on FiO2 > 30% and 66 who failed the room air challenge. Infants on room air (n=505) and those who passed the room air challenge (n=51) were classified as “no BPD” (n=556). At follow up, infants with BPD had significantly lower mean weight and head circumference. Moderate to severe cerebral palsy (7 vs. 2.1%) and spastic diplegia (7.8 vs. 4.1%) and quadriplegia (3.9 vs. 0.9%) phenotypes as well as cognitive (12.8 vs. 4.6%) and language scores < 70 (24.2 vs. 12.3%) were significantly more frequent in those with BPD compared to those without BPD. BPD was independently associated (adjusted OR 2.4; 95% CI 1.40-4.13) with cognitive impairment.
Rates of adverse neurodevelopmental outcomes in early childhood were significantly higher in those with BPD. BPD by the physiologic definition was independently associated with cognitive impairment using Bayley Scales III. These findings have implications for targeted post-discharge surveillance and early intervention.
PMCID: PMC3686277  PMID: 22236557
Outcome; preterm; bronchopulmonary dysplasia; physiologic definition
15.  Underdiagnosis of posterior communicating artery aneurysm in non-invasive brain vascular studies 
Expert interpretation of modern noninvasive neuroimaging such as CTA or MRA should detect nearly all aneurysms responsible for an isolated third nerve palsy. Whether a catheter angiogram should still be obtained in cases with negative CTA or MRA remains debated, and mostly relies on whether the noninvasive study was correctly performed and interpreted. The aim of our study was to review the diagnostic strategies used to evaluate patients with isolated aneurysmal third nerve palsy at a large academic center.
Retrospective review of all cases with posterior communicating artery (PCom A) aneurysmal third nerve palsies seen at our institution since 2001.
We identified 417 cases with third nerve palsy, aneurysm, or subarachnoid hemorrhage, among which 17 presented with an acute isolated painful third nerve palsy related to an ipsilateral PCom A aneurysm (mean age 52; range 33–83 years). Patients were classified into 3 groups based on the results of the noninvasive imaging obtained at initial presentation. Group I included 4 cases with subarachnoid hemorrhage on initial non-contrast head CT initially obtained in an emergency department for evaluation of their isolated third nerve palsy. Group II included 5 cases with isolated third nerve palsy and normal non-contrast head CT at presentation, immediately correctly diagnosed with a PCom A aneurysm at the referring institution. Group III included the 8 remaining cases who all had aneurysms that were missed on noninvasive studies at outside institutions. Review of these outside studies at our institution showed a PCom A aneurysm, confirming misinterpretation of these tests by the outside radiologists, rather than inadequate technique. Absence of specific training in neuroradiology and inaccurate clinical information provided to the interpreting radiologist were associated with test misinterpretation at the outside institutions. The average size of PCom A aneurysms causing an isolated third nerve palsy across all 3 groups was 7.3 mm, and was similar in each group.
Our study suggests that aside from an accurate history, the training and experience of the interpreting radiologist is probably the most important factor in determining the reliability of a noninvasive scan in patients with isolated third nerve palsies.
PMCID: PMC3682504  PMID: 21150642
16.  An Update on Idiopathic Intracranial Hypertension 
Reviews in neurological diseases  2010;7(0):e56-e68.
Idiopathic intracranial hypertension (IIH) is a condition of unknown etiology often encountered in neurologic practice. It produces non-localizing symptoms and signs of raised intracranial pressure and, when left untreated, can result in severe irreversible visual loss. It most commonly occurs in obese women of childbearing age, but it can also occur in children, men, non-obese adults, and older adults. While it is frequently associated with obesity, it can be associated with other conditions, such as obstructive sleep apnea and transverse cerebral venous sinus stenoses. Recent identification of subgroups at high risk for irreversible visual loss, including black patients, men, and patients with fulminant forms of IIH, help guide the optimal management and follow-up. Ongoing studies of venous anatomy and physiology in IIH patients, as well as a recently begun randomized clinical treatment trial, should provide more insights into this common yet poorly understood syndrome of isolated intracranial hypertension.
PMCID: PMC3674489  PMID: 20944524
Idiopathic Intracranial Hypertension; Venous Sinus Stenosis; Ventriculoperitoneal Shunting; Lumboperitoneal Shunting; Optic Nerve Sheath Fenestration; Venous Sinus Stenting
17.  Deafness and blindness as a presentation of colorectal meningeal carcinomatosis 
We present a unique case of a patient with deafness and blindness secondary to carcinomatous meningitis from colorectal adenocarcinoma with accompanying radiologic and pathologic images and a brief review of the relevant literature.
PMCID: PMC3674494  PMID: 20966893
meningeal carcinomatosis; severe visual loss; severe hearing loss
18.  Blood Pressure Threshold for Abnormal Ocular Fundus Findings is Lower than Expected 
Hypertension  2011;59(2):e8-e9.
PMCID: PMC3670697  PMID: 22203745
19.  Population Pharmacokinetics of Piperacillin Using Scavenged Samples from Preterm Infants 
Therapeutic Drug Monitoring  2012;34(3):312-319.
Piperacillin is often used in preterm infants for intra-abdominal infections; however, dosing has been derived from small single-center studies excluding extremely preterm infants at highest risk for these infections. We evaluated the population pharmacokinetics (PK) of piperacillin using targeted sparse sampling and scavenged samples obtained from preterm infants ≤32 weeks gestational age at birth and <120 postnatal days.
Materials and Methods
A 5-center study was performed. A population PK model using nonlinear mixed effect modeling was developed. Covariate effects were evaluated based on estimated precision and clinical significance.
Fifty-six preterm infants were evaluated and had a median (range) gestational age at birth of 25 (22–32) weeks, a postnatal age of 17 (1–77) days, a postmenstrual age of 29 (23–40) weeks, and a weight of 867 (400–2580) grams. The final PK data set contained 211 samples; 202/211 (96%) were scavenged from discarded clinical specimens. Piperacillin population PK was best described by a 1-compartment model. The population mean clearance (CL) was derived by the equation CL (liter/h)=0.479 x (weight)0.75 x 0.5/serum creatinine and using a volume of distribution (V) (liter) of 2.91 x (weight). The relative standard errors around parameter estimates ranged from 13.7–32.2%. A trend towards increased CL was observed with increasing gestational age at birth; infants with serum creatinine ≥1.2 mg/dL had a 60% reduction in piperacillin CL. The majority (>70%) of infants did not meet pre-defined pharmacodynamic efficacy targets.
Scavenged PK sampling is a minimal-risk approach that can provide meaningful information related to development of PK models but not dosing recommendations for piperacillin. The utility of scavenged sampling in providing definitive dosing recommendations may be drug-dependent and needs to be further explored.
PMCID: PMC3354042  PMID: 22569355
neonate; drug; pharmacokinetics; piperacillin
20.  Update on the pathophysiology and management of idiopathic intracranial hypertension 
Idiopathic Intracranial Hypertension (IIH) is a disease of unknown etiology typically affecting young, obese women, producing a syndrome of increased intracranial pressure without identifiable cause. Despite a large number of hypotheses and publications over the past decade, the etiology is still unknown. Vitamin A metabolism, adipose tissue as an actively secreting endocrine tissue, and cerebral venous abnormalities are areas of active study regarding IIH’s pathophysiology. There continues to be no evidence-based consensus or formal guidelines regarding management and treatment of the disease. Treatment studies show that the diagnostic lumbar puncture is a valuable intervention beyond its diagnostic importance, and that weight management is critical. However, open questions remain regarding the efficacy of acetazolamide, cerebrospinal fluid shunting procedures, and cerebral transverse venous sinus stenting.
PMCID: PMC3544160  PMID: 22423118
Idiopathic intracranial hypertension; pseudotumor cerebri; papilledema; cerebral venous stenosis; cerebral venous stenting; obesity
21.  Methicillin-Resistant and Susceptible Staphylococcus aureus Bacteremia and Meningitis in Preterm Infants 
Pediatrics  2012;129(4):e914-e922.
Data are limited on the impact of methicillin-resistant Staphylococcus aureus (MRSA) on morbidity and mortality among very low birth weight (VLBW) infants with S aureus (SA) bacteremia and/or meningitis (B/M).
Neonatal data for VLBW infants (birth weight 401–1500 g) born January 1, 2006, to December 31, 2008, who received care at centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network were collected prospectively. Early-onset (≤72 hours after birth) and late-onset (>72 hours) infections were defined by blood or cerebrospinal fluid cultures and antibiotic treatment of ≥5 days (or death <5 days with intent to treat). Outcomes were compared for infants with MRSA versus methicillin-susceptible S aureus (MSSA) B/M.
Of 8444 infants who survived >3 days, 316 (3.7%) had SA B/M. Eighty-eight had MRSA (1% of all infants, 28% of infants with SA); 228 had MSSA (2.7% of all infants, 72% of infants with SA). No infant had both MRSA and MSSA B/M. Ninety-nine percent of MRSA infections were late-onset. The percent of infants with MRSA varied by center (P < .001) with 9 of 20 centers reporting no cases. Need for mechanical ventilation, diagnosis of respiratory distress syndrome, necrotizing enterocolitis, and other morbidities did not differ between infants with MRSA and MSSA. Mortality was high with both MRSA (23 of 88, 26%) and MSSA (55 of 228, 24%).
Few VLBW infants had SA B/M. The 1% with MRSA had morbidity and mortality rates similar to infants with MSSA. Practices should provide equal focus on prevention and management of both MRSA and MSSA infections among VLBW infants.
PMCID: PMC3313632  PMID: 22412036
Staphylococcus aureus; methicillin resistant; infant; newborn
22.  Enrollment of Extremely Low Birth Weight Infants in a Clinical Research Study May Not Be Representative 
Pediatrics  2012;129(3):480-484.
The Surfactant Positive Airway Pressure and Pulse Oximetry Randomized Trial (SUPPORT) antenatal consent study demonstrated that mothers of infants enrolled in the SUPPORT trial had significantly different demographics and exposure to antenatal steroids compared with mothers of eligible, but not enrolled infants. The objective of this analysis was to compare the outcomes of bronchopulmonary dysplasia, severe retinopathy of prematurity, severe intraventricular hemorrhage or periventricular leukomalacia (IVH/PVL), death, and death/severe IVH/PVL for infants enrolled in SUPPORT in comparison with eligible, but not enrolled infants.
Perinatal characteristics and neonatal outcomes were compared for enrolled and eligible but not enrolled infants in bivariate analyses. Models were created to test the effect of enrollment in SUPPORT on outcomes, controlling for perinatal characteristics.
There were 1316 infants enrolled in SUPPORT; 3053 infants were eligible, but not enrolled. In unadjusted analyses, enrolled infants had significantly lower rates of death before discharge, severe IVH/PVL, death/severe IVH/PVL (all < 0.001), and bronchopulmonary dysplasia (P = .003) in comparison with eligible, but not enrolled infants. The rate of severe retinopathy of prematurity was not significantly different. After adjustment for perinatal factors, enrollment in the trial was not a significant predictor of any of the tested clinical outcomes.
The results of this analysis demonstrate significant outcome differences between enrolled and eligible but not enrolled infants in a trial using antenatal consent, which were likely due to enrollment bias resulting from the antenatal consent process. Additional research and regulatory review need to be conducted to ensure that large moderate-risk trials that require antenatal consent can be conducted in such a way as to ensure the generalizability of results.
PMCID: PMC3289530  PMID: 22371462
antenatal steroids; clinical research/trials; informed consent; neonatal
23.  Quality of non-mydriatic digital fundus photography obtained by nurse practitioners in the emergency department: the FOTO-ED study 
Ophthalmology  2012;119(3):617-624.
Non-mydriatic fundus photography by non-ophthalmic trained personnel has recently been shown to be a potential alternative to direct ophthalmoscopy in the emergency department (ED). We evaluated the reliability of a novel quality rating scale and applied this scale to non-mydriatic fundus photographs taken during routine ED patient encounters to determine factors associated with diminished photograph quality.
Prospective, cross-sectional
350 patients enrolled in the Fundus photography vs. Ophthalmoscopy Trials Outcomes in the Emergency Department (FOTO-ED) study were photographed by nurse practitioners after <30 minutes of training followed by supervision.
Photographs of both eyes were graded for quality on two occasions by two neuro-ophthalmologists. Four regions were independently evaluated for quality: optic disc, macula, superior and inferior vascular arcades. Quality as a function of the number of photographs taken was evaluated by Kaplan-Meier analysis. Mixed effects ordinal logistic regression was used to evaluate for predictors of image quality while accounting for the repeated measures design.
Main Outcome Measure
Overall photographic quality (1–5 scale, 5 best).
We evaluated 1734 photographs. Inter- and intra-observer agreements between neuro-ophthalmologists were very good (weighted kappa:0.84–0.87). Quality of the optic disc area was better than those of other retinal areas (p<0.002). Kaplan-Meier analysis showed that if a high-quality photograph of an eye was not obtained by the third attempt it was unlikely that one would be obtained at all. A 10 second increase in the inter-photograph interval before a total of forty seconds increased the odds of a one unit higher quality rating by 1.81 times (95%CI: 1.68–1.98), and a ten year increase in age decreased the odds by 0.76 times (95%CI: 0.69–0.85). Black patients had 0.42 times (95%CI: 0.28–0.63) the odds of a one unit higher quality rating compared to whites.
Our 5-point scale is a reliable measure of non-mydriatic photograph quality. The region of interest, interphotograph interval, age, and race are significant predictors of image quality for non-mydriatic photographs taken by nurse practitioners in the ED. Addressing these factors may have a direct impact on the successful implementation of non-mydriatic fundus photography into the ED.
PMCID: PMC3294008  PMID: 22218140
24.  Optic nerve head drusen in black patients 
Several studies have suggested racial differences in the prevalence of optic nerve head drusen (ONHD). We aimed to determine the percentage of patients with ONHD who are black, and to describe the clinical, ophthalmoscopic, and perimetry findings in these patients.
We conducted a retrospective chart review of all patients with ONHD seen at our institution between 1989 and 2010. Only black patients with ONHD confirmed on either funduscopy or B-scan ultrasonography were included. Demographic and clinical findings in these patients were recorded and analyzed.
Of 196 patients with confirmed ONHD, 10 (5.1%) were black (7 women; ages 8–61 years). Six of the 10 patients had bilateral ONHD. The ONHD were buried in 11 of 16 eyes with ONHD, and exposed in 5 of 16 eyes. Fifteen of 16 eyes with ONHD had small cupless optic nerve heads. Visual fields were normal in 4 of 16 eyes with ONHD. In the other eyes, visual field defects included an enlarged blind spot (5 eyes), constricted field (5 eyes), nasal defect (2 eyes), central defect (1 eye), and generalized depression (1 eye). Visual field defects were present in 4 of 5 eyes (80%) with exposed ONHD and 8 of 11 eyes (72.7%) with buried ONHD. None of the patients were related and none of their examined family members had exposed ONHD on funduscopic examination.
ONHD are rare in blacks, possibly due to the presence of a larger cup-to-disc ratio or a lack of predisposing genetic factors. Visual field defects are common in black patients with both exposed and buried ONHD.
PMCID: PMC3459063  PMID: 21788909
Optic Nerve; Drusen; Ethnicity
25.  Association of antenatal corticosteroids with mortality and neurodevelopmental outcomes among infants born at 22–25 weeks gestation 
Current guidelines, initially published in 1995, recommend antenatal corticosteroids for mothers with preterm labor from 24–34 weeks gestational age, but not before 24 weeks because of lack of data. However, many infants born before 24 weeks are provided intensive care now.
To determine if antenatal corticosteroids are associated with improvement in major outcomes in infants born at 22 and 23 weeks.
Design, Setting, Participants
Data for this cohort study were collected prospectively on 401–1000 gram inborn infants (N=10,541) of 22–25 weeks gestation born between 1993–2009 at 23 academic perinatal centers in the United States. Certified examiners unaware of exposure to antenatal corticosteroids performed follow-up examinations on 4,924 (86.5%) of the infants born in 1993–2008 who survived to 18–22 months. Logistic regression models generated adjusted odds ratios, controlling for maternal and neonatal variables.
Main Outcome Measures
Mortality and neurodevelopmental impairment at 18–22 months corrected age
Death or neurodevelopmental impairment at 18–22 months was lower for infants whose mothers received antenatal corticosteroids born at 23 weeks (antenatal corticosteroids, 83.4% vs no antenatal corticosteroids, 90.5%; adjusted odds ratio 0.58; 95% CI, 0.42–0.80), at 24 weeks (antenatal corticosteroids, 68.4% vs no antenatal corticosteroids, 80.3%; adjusted odds ratio 0.62; 95% CI, 0.49–0.78), and at 25 weeks (antenatal corticosteroids, 52.7% vs no antenatal corticosteroids, 67.9%; adjusted odds ratio 0.61; 95% CI, 0.50–0.74) but not at 22 weeks (antenatal corticosteroids, 90.2% vs no antenatal corticosteroids, 93.1%; adjusted odds ratio 0.80; 95% CI, 0.29–12.21). Death by 18–22 months, hospital death, death/intraventricular hemorrhage/periventricular leukomalacia, and death/necrotizing enterocolitis were significantly lower for infants born at 23, 24, and 25 weeks gestational age if the mothers had received antenatal corticosteroids but the only outcome significantly lower at 22 weeks was death/necrotizing enterocolitis (antenatal corticosteroids, 73.5% vs no antenatal corticosteroids, 84.5%; adjusted odds ratio 0.54; 95% CI, 0.30–0.97).
Among infants born at 23–25 weeks gestation, use of antenatal corticosteroids compared to non-use was associated with a lower rate of death or neurodevelopmental impairment at 18–22 months.
PMCID: PMC3565238  PMID: 22147379
prematurity; infant mortality; neonatal intensive care; neurodevelopmental impairment; lung maturation; limits of viability

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