BACKGROUND AND OBJECTIVE:
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.
antenatal steroids; clinical research/trials; informed consent; neonatal
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.
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.
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.
Optic Nerve; Drusen; Ethnicity
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.
prematurity; infant mortality; neonatal intensive care; neurodevelopmental impairment; lung maturation; limits of viability
To examine pathogens and other characteristics associated with late-onset bloodstream infections (BSI) in infants with intestinal failure (IF) as a consequence of necrotizing enterocolitis (NEC).
Infants 401–1500 grams at birth who survived >72 hours and received care at NICHD Neonatal Research Network centers were studied. Frequency of culture positive BSI and pathogens were compared for infants with medical NEC, NEC managed surgically without IF, and surgical IF. Among infants with IF, duration of parenteral nutrition (PN) and other outcomes were evaluated.
932 infants were studied (IF, n=78; surgical NEC without IF, n=452; medical NEC, n=402). The proportion with BSI after NEC diagnosis was higher in infants with IF than with surgical NEC (p=0.007) or medical NEC (p<0.001). Gram positive pathogens were most frequent. Among infants with IF, increased number of infections was associated with longer hospitalization and duration on PN (0, 1, ≥2 infections; median stay (days): 172, 188, 260, p=0.06; median days on PN: 90, 112, 115, p=0.003), and the proportion who achieved full feeds during hospitalization decreased (87%, 67%, 50%, p=0.03).
Recurrent BSIs are common in VLBW infants with IF. Gram positive bacteria were most commonly identified in these infants.
Short bowel syndrome; Bloodstream infections; Late onset sepsis; Very low birth weight; Nutrition; Intestinal failure
Ocular funduscopic examination is difficult in young children and is rarely attempted by nonophthalmologists. Our objective was to determine the feasibility of reliably obtaining high-quality nonmydriatic fundus photographs in children.
Nonmydriatic fundus photographs were obtained in both eyes of children seen in a pediatric ophthalmology clinic. Ease of fundus photography was recorded on a 10-point Likert scale (10 = very easy). Quality was graded from 1 to 5 (1, inadequate for any diagnostic purpose; 2, unable to exclude all emergent findings; 3, only able to exclude emergent findings; 4, not ideal, but still able to exclude subtle findings; and 5, ideal quality). The primary outcome measure was image quality by age.
A total of 878 photographs of 212 children (median age, 6 years; range,1-18 years) were included. Photographs of at least one eye were obtained in 190 children (89.6%) and in both eyes in 181 (85.3%). Median rating for ease of photography was 7. Photographs of some clinical value (grade ≥2) were obtained in 33% of children <3 years and 95% >3 years. High-quality photographs (grade 4 or 5) were obtained in both eyes in 7% of children <3 years, 57% of children ≥3 to <7 years, 85% of children ≥7 to <9 years, and 65% of children ≥9 years. The youngest patient with high-quality photographs in both eyes was 22 months.
Nonmydriatic fundus photographs of adequate quality can be obtained in children over age 3 and in some children as young as 22 months.
Hypertensive retinopathy describes a spectrum of retinal changes in patients with elevated blood pressure (BP). It is unknown why some patients are more likely to develop acute ocular end-organ damage than others with similar BP. We examined risk factors for grade III/IV hypertensive retinopathy among patients with hypertensive urgency in the emergency department (ED) and compared healthcare utilization and mortality between patients with and without grade III/IV hypertensive retinopathy.
A preplanned subanalysis of patients who presented to a university hospital ED with diastolic BP ≥ 120 mmHg and who enrolled in the Fundus Photography versus Ophthalmoscopy Trial Outcomes in the ED study was performed. Bilateral nonmydriatic ocular fundus photographs, vital signs, and demographics were obtained at presentation. Past medical history, laboratory values, healthcare utilization, and mortality were ascertained from medical record review at least 8 months after initial ED visit.
Twenty-one patients with diastolic BP ≥ 120 mmHg, 7 of whom (33%) had grade III/IV hypertensive retinopathy, were included. Patients with retinopathy were significantly younger than those without (median 33 vs 50 years, P= 0.02). Mean arterial pressure (165 vs 163 mmHg) was essentially equal in the 2 groups. Patients with retinopathy had substantially increased but nonsignificant rates of ED revisit (57% vs 29%, P = 0.35) and hospital admission after ED discharge (43% vs 14%, P = 0.28). One of the patients with retinopathy died, but none without.
Younger patients may be at higher risk for grade III/IV hypertensive retinopathy among patients with hypertensive urgency. Chronic compensatory mechanisms may have not yet developed in these younger patients. Alternatively, older patients with retinopathy may be underrepresented secondary to increased mortality among these patients at a younger age (survivorship bias). Further research is needed to validate these preliminary findings.
stroke; ischemia; carotid artery; vertebra-basilar circulation; retinopathy
Pharmacokinetic (PK) studies in preterm infants are rarely conducted due to the research challenges posed by this population. To overcome these challenges, minimal-risk methods such as scavenged sampling can be used to evaluate the PK of commonly used drugs in this population. We evaluated the population PK of metronidazole using targeted sparse sampling and scavenged samples from infants that were ≤32 weeks of gestational age at birth and <120 postnatal days. A 5-center study was performed. A population PK model using nonlinear mixed-effect modeling (NONMEM) was developed. Covariate effects were evaluated based on estimated precision and clinical significance. Using the individual Bayesian PK estimates from the final population PK model and the dosing regimen used for each subject, the proportion of subjects achieving the therapeutic target of trough concentrations >8 mg/liter was calculated. Monte Carlo simulations were performed to evaluate the adequacy of different dosing recommendations per gestational age group. Thirty-two preterm infants were enrolled: the median (range) gestational age at birth was 27 (22 to 32) weeks, postnatal age was 41 (0 to 97) days, postmenstrual age (PMA) was 32 (24 to 43) weeks, and weight was 1,495 (678 to 3,850) g. The final PK data set contained 116 samples; 104/116 (90%) were scavenged from discarded clinical specimens. Metronidazole population PK was best described by a 1-compartment model. The population mean clearance (CL; liter/h) was determined as 0.0397 × (weight/1.5) × (PMA/32)2.49 using a volume of distribution (V) (liter) of 1.07 × (weight/1.5). The relative standard errors around parameter estimates ranged between 11% and 30%. On average, metronidazole concentrations in scavenged samples were 30% lower than those measured in scheduled blood draws. The majority of infants (>70%) met predefined pharmacodynamic efficacy targets. A new, simplified, postmenstrual-age-based dosing regimen is recommended for this population. Minimal-risk methods such as scavenged PK sampling provided meaningful information related to development of metronidazole PK models and dosing recommendations.
Many studies have shown that hypertensive ocular funduscopic abnormalities are clearly related to stroke, even after controlling for level of blood pressure and other vascular risk factors. Retinal abnormalities indicative of a breakdown of the blood-retina barrier confer a greater increase in risk for stroke than sclerotic retinal changes. Similar retinal changes also have a positive relationship with stroke mortality. Hypertensive ocular fundus abnormalities are also reported to be associated with an increased risk for cognitive impairment, cerebral atrophy, progression of MRI-defined white matter lesions, and subclinical infarction. Recent advances in fundus photography allow for improved accuracy and consistency in interpretation of funduscopic lesions, and improve the feasibility of screening for these abnormalities in at-risk patient populations. Evaluating the ocular fundus for signs of hypertensive retinopathy, in combination with an assessment of the presence or absence of other known vascular risk factors, may allow clinicians to further individualize a risk profile for stroke to each individual patient, thus permitting more accurate risk stratification and, potentially, guiding treatment strategies.
Examination of the ocular fundus is imperative in many acute medical and neurologic conditions, but direct ophthalmoscopy by non-ophthalmologists is underutilized, poorly performed, and difficult without pharmacologic pupillary dilation. The objective was to examine the feasibility of non-mydriatic fundus photography as a clinical alternative to direct ophthalmoscopy by emergency physicians (EPs).
Adult patients presenting to the emergency department (ED) with headache, acute focal neurologic deficit, diastolic blood pressure ≥ 120 mmHg, or acute visual change had ocular fundus photographs taken by nurse practitioners using a non-mydriatic fundus camera. Photographs were reviewed by a neuro-ophthalmologist within 24 hours for findings relevant to acute ED patient care. Nurse practitioners and patients rated ease, comfort, and speed of non-mydriatic fundus photography on a 10-point Likert scale (10 best). Timing of visit and photography were recorded by automated electronic systems.
Three hundred fifty patients were enrolled. There were 1,734 photographs taken during 230 nurse practitioner shifts. Eighty-three percent of the 350 patients had at least one eye with a high quality photograph, while only 3% of patients had no photographs of diagnostic value. Mean ratings were ≥ 8.7 (standard deviation [SD] ≤ 1.9) for all measures. The median photography session lasted 1.9 minutes (interquartile range [IQR] 1.3 to 2.9 minutes), typically accounting for less that 0.5% of the patient’s total ED visit.
Non-mydriatic fundus photography taken by nurse practitioners is a feasible alternative to direct ophthalmoscopy in the ED. It is performed well by non-physician staff, is well-received by staff and patients, and requires a trivial amount of time to perform.
Provide an update on various features of idiopathic intracranial hypertension.
Selected articles on the epidemiology, clinical and imaging features, natural history, pathophysiology, and treatment of idiopathic intracranial hypertension were reviewed and interpreted in the context of the authors’ clinical and research experience.
Idiopathic intracranial hypertension is primarily a disease of obese women of childbearing age, but it can affect patients of any weight, sex, and age. Although a relatively rare disorder, idiopathic intracranial hypertension’s associated costs in the U.S. entail hundreds of millions of dollars. Even following treatment, headaches are frequently persistent and may require the continued involvement of a neurologist. Quality of life reductions and depression are common among idiopathic intracranial hypertension patients. However, visual dysfunction, especially visual field abnormalities, represents the major morbidity of this disorder, and serial automated perimetry remains the primary mode of patient monitoring. Patients who are men, black, very obese, or anemic are at higher risk of visual loss. Vitamin A metabolism, adipose tissue as an actively secreting endocrine tissue, and cerebral venous abnormalities are areas of active study regarding idiopathic intracranial hypertension’s pathophysiology. Treatment studies show that lumbar puncture is a valuable treatment (in addition to its crucial diagnostic role) and that weight management is critical. However, open questions remain regarding the efficacy of acetazolamide, CSF diversion procedures, and cerebral venous stenting.
Many questions remain unanswered about idiopathic intracranial hypertension. Ongoing studies, especially an ongoing NIH-funded clinical trial of acetazolamide, should provide more insight into this important, yet poorly understood syndrome of isolated intracranial hypertension.
Idiopathic Intracranial Hypertension; Venous Sinus Stenosis; Ventriculoperitoneal Shunting; Lumboperitoneal Shunting; Optic Nerve Sheath Fenestration; Venous Sinus Stenting
Rationale: Benefits of identifying risk factors for bronchopulmonary dysplasia in extremely premature infants include providing prognostic information, identifying infants likely to benefit from preventive strategies, and stratifying infants for clinical trial enrollment.
Objectives: To identify risk factors for bronchopulmonary dysplasia, and the competing outcome of death, by postnatal day; to identify which risk factors improve prediction; and to develop a Web-based estimator using readily available clinical information to predict risk of bronchopulmonary dysplasia or death.
Methods: We assessed infants of 23–30 weeks' gestation born in 17 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network and enrolled in the Neonatal Research Network Benchmarking Trial from 2000–2004.
Measurements and Main Results: Bronchopulmonary dysplasia was defined as a categorical variable (none, mild, moderate, or severe). We developed and validated models for bronchopulmonary dysplasia risk at six postnatal ages using gestational age, birth weight, race and ethnicity, sex, respiratory support, and FiO2, and examined the models using a C statistic (area under the curve). A total of 3,636 infants were eligible for this study. Prediction improved with advancing postnatal age, increasing from a C statistic of 0.793 on Day 1 to a maximum of 0.854 on Day 28. On Postnatal Days 1 and 3, gestational age best improved outcome prediction; on Postnatal Days 7, 14, 21, and 28, type of respiratory support did so. A Web-based model providing predicted estimates for bronchopulmonary dysplasia by postnatal day is available at https://neonatal.rti.org.
Conclusions: The probability of bronchopulmonary dysplasia in extremely premature infants can be determined accurately using a limited amount of readily available clinical information.
bronchopulmonary dysplasia; prematurity; low-birth-weight infant
Autosomal-dominant optic atrophy (DOA) is one of the most common inherited optic neuropathies, and it is genetically heterogeneous, with mutations in both OPA1 and OPA3 known to cause disease. About 60% of cases harbor OPA1 mutations, whereas OPA3 mutations have only been reported in two pedigrees with DOA and premature cataracts. The aim of this study was to determine the yield of OPA1 and OPA3 screening in a cohort of presumed DOA cases referred to a tertiary diagnostic laboratory.
Retrospective case series.
One hundred and eighty-eight probands with bilateral optic atrophy referred for molecular genetic investigations at a tertiary diagnostic facility: 38 patients with an autosomal-dominant pattern of inheritance and 150 sporadic cases.
OPA1 and OPA3 genetic testing was initially performed using PCR-based sequencing methods. The presence of large-scale OPA1 and OPA3 genomic rearrangements was further assessed with a targeted comparative genomic hybridization (CGH) microarray platform. The three primary Leber hereditary optic neuropathy (LHON) mutations, m.3460G>A, m.11778G>A, and m.14484T>C, were also screened in all patients.
Main Outcome Measures
The proportion of patients with OPA1 and OPA3 pathogenic mutations. The clinical profile observed in molecularly confirmed DOA cases.
We found 21 different OPA1 mutations in 27 of the 188 (14.4%) probands screened. The mutations included six novel pathogenic variants and the first reported OPA1 initiation codon mutation at c.1A>T. An OPA1 missense mutation, c.239A>G (p.Y80C), was identified in an 11-year-old African-American girl with optic atrophy and peripheral sensori-motor neuropathy in her lower limbs. The OPA1 detection rate was significantly higher among individuals with a positive family history of visual failure (50.0%) compared with sporadic cases (5.3%). The primary LHON screen was negative in our patient cohort, and additional molecular investigations did not reveal any large-scale OPA1 rearrangements or OPA3 genetic defects. The mean baseline visual acuity for our OPA1-positive group was 0.48 logarithm of the minimum angle of resolution (LogMAR) (Mean Snellen equivalent = 20/61, range = 20/20–20/400, 95% confidence interval = 20/52–20/71), and visual deterioration occurred in 54.2% of patients during follow-up.
OPA1 mutations are the most common genetic defects identified in patients with suspected DOA, whereas OPA3 mutations are very rare in isolated optic atrophy cases.
Neurologists frequently evaluate patients complaining of vision loss, especially when the patient has been examined by an ophthalmologist who has found no ocular disease. A significant proportion of patients presenting to the neurologist with visual complaints will have non-organic or functional visual loss. While there are examination techniques which can aid in the detection and diagnosis of functional visual loss, the frequency with which functional visual loss occurs concomitantly with organic disease warrants substantial caution on the part of the clinician. Furthermore, purely functional visual loss is never a diagnosis of exclusion, and must be supported by positive findings on examination that demonstrate normal visual function. The relationship of true psychological disease and functional visual loss is unclear and most patients respond well to simple reassurance.
functional visual loss; nonorganic visual loss
Because the retina has high energy demands, the loss of a mitochondrial ATP transporter was predicted to impact retinal function. The authors examined retinal function and morphology in mice without ANT1, a key ATP transporter associated with myopathy.
Mutations in ANT, a mitochondrial ATP transporter, are typically associated with myopathy. Because of the high metabolic demands of the retina, the authors examined whether elimination of the Ant1 isoform in a transgenic mouse affects retinal function or morphology.
RT-PCR was used to confirm Ant1 expression in retinas of wild-type (WT) or Ant1−/− mice. Full-field ERGs were used to test retinal function under dark- and light-adapted conditions and the recovery of the photoresponse to a bright flash. Using histologic methods, the authors assessed the retinal location of ANT and ANT1-β-gal reporter protein, mitochondrial activity with cytochrome c oxidase (COX) and succinate dehydrogenase (SDH) staining, retinal layer thickness, and bipolar cell types using Chx10 and recoverin.
Ant1−/− mice had supernormal ERG b-waves under both dark- and light-adapted conditions. X-Gal staining was detected in a subset of cells within the inner retina. The following characteristics were normal in Ant1−/− mice compared with age-matched WT mice: recovery of the photoresponse, COX and SDH activity, retinal morphology, and bipolar cell morphology.
The presence of ANT1 in a subset of inner retinal cells accompanied by supernormal ERG responses suggests that ANT1 may be localized to hyperpolarizing bipolar cells. However, the immunohistochemical techniques used here did not show any differences in bipolar cells. Moderate functional changes coupled with a lack of detectable morphologic changes suggest that ANT1 is not essential for ATP transport in the retina.
To identify risk factors for idiopathic intracranial hypertension (IIH) in men
Case-control study. A 96-item telephone questionnaire, answered retrospectively, with cases recalling at the age of their diagnosis and controls recalling at the age of their corresponding case's diagnosis.
Outpatient clinics in two US tertiary care centers
The characteristics of 24 men with IIH were compared to those of 48 controls matched for sex, age, race, and World Health Organization body mass index (BMI) category.
Main Outcome Measures
Two previously validated questionnaires: the ADAM (Androgen Deficiency in Aging Males) questionnaire for testosterone deficiency and the Berlin questionnaire for obstructive sleep apnea (OSA), embedded within the telephone questionnaire. Analysis with Mantel-Haenszel odds ratios and mixed-effects logistic regression models accounted for matching.
Cases and controls had similar enrollment matching characteristics. Although matching was successful by BMI category, there was a small difference between BMI values of cases and controls (cases: median 31.7, controls: median 29.9; p=0.03). After adjustment by BMI value, men with IIH were significantly more likely than controls to have a positive ADAM questionnaire for testosterone deficiency (OR: 17.4, 95% CI: 5.6-54.5; p<0.001) and significantly more likely to have either a positive Berlin questionnaire for OSA or history of diagnosed OSA (OR: 4.4, 95% CI: 1.5-12.9; p=0.03).
Men with IIH are more likely than controls to have symptoms associated with testosterone deficiency and OSA. These associations suggest a possible role for sex hormones and OSA in the pathogenesis of IIH in men.
idiopathic intracranial hypertension; gender differences; androgen deficiency; sleep apnea; risk factors; neuro-ophthalmology
The purposes of this study were to quantify the time and effort involved in obtaining prenatal consent for the Neonatal Research Network Surfactant Positive Airway Pressure and Pulse Oximetry Randomized Trial (SUPPORT) and to determine whether the enrolled infants were representative of the eligible population.
Eligible subjects were likely to deliver in the SUPPORT gestational age window (24–27 6/7; weeks). Data included who approached the subjects for consent, how often they approached, the duration of each contact, whether consent was obtained, and whether subjects were enrolled in the trial. Eligible, nonenrolled infants entered into the Neonatal Research Network Generic Database throughout the period of SUPPORT enrollment were compared with enrolled infants.
A total of 2826 women were identified at 18 sites, 2228 were approached for consent, and 1219 (54.7%) agreed. For 76.9% of those approached, <3 visits (mean: 2.0 ± 1.2 visits) were required to complete the consent process. Of the 659 infants with consent who were delivered within the study window, 611 were enrolled. Mothers who received a neonatal consultation were more likely to give consent (P < .001). The proportion of infants not exposed to steroids was significantly greater in the nonapproached group than in the approached group (20.0% vs 3.4%; P < .0001).
In a trial that involved preterm infants and required prenatal consent, >5 women were identified as being likely to deliver in the SUPPORT gestational age window for each 1 who delivered an enrolled infant.
informed consent; prenatal; neonatal
Although giant cell arteritis (GCA) is a well-known vasculitis sensitive to corticosteroid-mediated immunosuppression, numerous issues of long-term therapeutic management remain unresolved. Because GCA encompasses a broad spectrum of clinical subtypes, ranging from devastating visual loss and neurological deficits to isolated systemic symptoms, the treatment of GCA must be adjusted to each case, and recommendations vary widely in the literature. This article systematically reviews the treatment options for patients with neuro-ophthalmic and neurological complications of GCA, as well as the evidence for possible adjuvant therapies for patients with GCA. Although there is no randomized controlled clinical trial specifically evaluating GCA patients with ocular and neurological complications, we recommend that GCA patients with acute visual loss or brain ischemia be admitted to the hospital for high-dose intravenous methyl-prednisolone, close monitoring, and prevention of steroid-induced complications. Aspirin may also be helpful in these cases. The evidence supporting the use of steroid-sparing immunomodulatory agents such as methotrexate for long-term management remains debated.
Arteritic ischemic optic neuropathy; Giant cell arteritis; Steroids; Stroke; Temporal arteritis
To evaluate racial differences in idiopathic intracranial hypertension (IIH).
Medical records of all consecutive patients with definite IIH seen between 1989 and 2006 were reviewed. Demographics, associated factors, and visual function at presentation and follow-up were collected. Black patients were compared to non-black patients.
We included 450 patients (197 black, 253 non-black). Obesity, systemic hypertension, anemia, and sleep apnea were more common in blacks than in non-blacks (p≤0.01). Cerebrospinal fluid opening pressure was higher in blacks (40 vs. 34 cm CSF, p<0.001). Visual acuity, visual field loss, and degree of papilledema at presentation and follow-up were worse in blacks (p≤0.01). Diagnostic and therapeutic measures were similar between blacks and non-blacks, except for optic nerve sheath fenestration (p=0.01) and lumbar puncture (p=0.03), both more commonly performed on black patients. The relative risk of severe visual loss for blacks compared with non-blacks was 3.5 (95%CI 2.0–5.8, p<0.001) in at least one eye and 4.8 (95%CI 2.1–10.9, p<0.001) in both eyes. Logistic regression analysis supported race, anemia, body mass index, and male gender as independent risk factors for severe visual loss and suggested that racial differences may be partially accounted for by differences in CSF opening pressure, body mass index, and frequency of anemia.
Black IIH patients were more likely than non-black IIH patients to have severe visual loss in at least one eye. This difference did not appear to result from diagnosis, treatment, or access to care, but may partially relate to differences in other risk factors. Black patients have a more aggressive disease and may need closer follow-up and lower thresholds for early intervention.
Optical coherence tomography (OCT) is a non-invasive imaging technique routinely used in ophthalmology to visualize and quantify the layers of the retina. It also provides information on optic nerve head topography, peripapillary retinal nerve fiber layer thickness, and macular volume which correlate with axonal loss. These measurements are of particular interest in optic neuropathies and in multiple sclerosis, and OCT parameters are now used as endpoints in neurologic clinical trials.
Optical Coherence Tomography; névrite optique; sclérose en plaques
Pain is a common feature of microvascular ischemic ocular motor cranial nerve palsies (MP). The natural history of pain in this condition has not been studied. The purpose of this report is to define the spectrum of pain in isolated MP, with special reference to diabetics versus nondiabetics.
Design and methods
Retrospective and prospective chart review was performed on 87 patients with acute onset MP of a single cranial nerve (CN III = oculomotor, CN IV = trochlear, or CN VI = abducens) that progressively improved or resolved over 6 months.
Five of the 87 patients had two events, making the total number events 92. There were 48 (52.2%) CN VI palsies, 39 (42.4%) CN III palsies, and 5 (5.4%) CN IV palsies. Thirty-six (41%) patients had diabetes. Pain was present in 57 (62%) events. The majority of diabetics and non-diabetics had pain. Pain preceded diplopia by 5.8 days (± 5.5) in one third of events. There was a trend towards greater pain with CN III palsies but this was not statistically significant. Patients who experienced severe pain tended to have pain for a longer duration of time (26.4 ± 21.7 days compared to 10.8 ± 8.3 and 9.5 ± 9 days for mild and moderate pain, respectively). There was no correlation between having diabetes and experiencing pain.
The majority of MP are painful, regardless of the presence or absence of diabetes. Pain may occur prior to or concurrent with the onset of diplopia. Nondiabetics and diabetics presented with similar pain characteristics, contrary to the belief that diabetics have more pain associated with MP.
Microvascular; cranial nerve; pain
Visual loss following head trauma is common, and the diagnosis can be challenging for the neurologist called to perform an emergency room assessment. The approach to the patient with post-traumatic visual loss is complicated by a wide range of potential ocular and brain injuries with varying pathophysiology. In addition to direct injuries of the eye and orbit, traumatic optic neuropathies, carotid cavernous fistulas, and damage to the intracranial visual pathways are classic causes of visual loss after head trauma. This review provides an update on the diagnosis and management of these conditions.
Carotid cavernous fistula; Traumatic brain injury; Traumatic optic neuropathy; Visual field defect; Visual loss