Efficacy and Safety of Sarilumab for the Treatment of Posterior Segment Noninfectious Uveitis (SARIL-NIU):: The Phase 2 SATURN Study.

PURPOSE: To assess efficacy and safety of sarilumab, a human anti-interleukin-6 receptor antibody, for treatment of posterior segment noninfectious uveitis (NIU). DESIGN: Randomized, double-masked, placebo-controlled, phase 2 study. PARTICIPANTS: Fifty-eight patients (eyes) with noninfectious intermediate, posterior, or panuveitis. METHODS: Eyes received treatment every 2 weeks for 16 weeks with subcutaneous sarilumab 200 mg or placebo. MAIN OUTCOME MEASURES: The primary end point was the proportion of patients with ≥2-step reduction in vitreous haze (VH) on the Miami scale or with a reduction of systemic corticosteroids (prednisolone or equivalent) to a dose of <10 mg/day at week 16. Primary end point was based on VH evaluation by a central reading center. Investigator evaluation of VH was a prespecified, planned secondary analysis. RESULTS: At week 16, proportion of patients taking sarilumab or placebo with ≥2-step reduction in VH or corticosteroid dose <10 mg/day was 46.1% vs. 30.0% (P = 0.2354) based on central reading center assessment of VH and 64.0% vs. 35.0% (P = 0.0372) based on investigator assessment of VH, respectively. In the subgroup of eyes with VH grade ≥2 at baseline, the mean VH reduction from baseline to week 16 was significantly greater with sarilumab vs. placebo regardless of assessment by the central reading center (-2.1 [n = 11] vs. -1.7 [n = 3], respectively; P = 0.0255) or investigator (-2.5 [n = 19] vs. -1.2 [n = 11], respectively; P = 0.0170). The mean best-corrected visual acuity gain from baseline to week 16 was greater with sarilumab vs. placebo in the overall population (8.9 vs. 3.6 letters, respectively; P = 0.0333) and in the subgroup of eyes with central subfield thickness (CST) ≥300 µm at baseline (12.2 [n = 13] vs. 2.1 [n = 7] letters, respectively; P = 0.0517). Corresponding changes in CST were -46.8 vs. +2.6 µm (P = 0.0683) in the overall population and -112.5 [n = 13] vs. -1.8 [n = 6] µm (P = 0.1317) in the subgroup of eyes with CST ≥300 µm at baseline, respectively. The most common ocular adverse events were worsening of uveitis (0 [placebo] and 3 [sarilumab] patients) and retinal infiltrates (1 [placebo] and 2 [sarilumab] patients). CONCLUSIONS: Subcutaneous sarilumab may provide clinical benefits in the management of NIU of the posterior segment, especially in eyes with uveitic macular edema.

Effects of Repeated Intravitreal Aflibercept Injection on the Corneal Endothelium in Patients With Age-Related Macular Degeneration: Outcomes From the RE-VIEW Study.

PURPOSE: The effects of repeated intravitreal aflibercept injection (IAI) on the corneal endothelium were studied in patients with unilateral neovascular age-related macular degeneration. METHODS: RE-VIEW was a phase 4, open-label, single-arm, multicenter study. Patients received IAI every 8 weeks after 3 monthly doses. Slit-lamp biomicroscopy was performed at all study visits. The central corneal endothelial health was evaluated by specular microscopy in the treated versus untreated fellow eyes at baseline and weeks 24 and 52. RESULTS: No slit-lamp abnormalities were noted in 154 enrolled patients (eyes). Baseline versus 52-week mean (±SD) endothelial morphometric values (n = 118) for the treated versus untreated fellow eyes were respectively as follows: endothelial cell density was 2410 ± 364 versus 2388 ± 384 cells/mm at baseline and remained unchanged at 2401 ± 353 versus 2376 ± 364 cells/mm at 52 weeks (P = 0.87); the coefficient of variation was 33.5 ± 4.4% versus 34.0 ± 5.0% at baseline and remained unchanged at 34.2 ± 4.7% versus 34.1 ± 4.9% at 52 weeks (P = 0.18); the percentage of hexagonal cells was 59.5 ± 5.8% versus 59.6 ± 6.4% at baseline and remained unchanged at 59.5 ± 6.0% versus 59.5 ± 5.8% at 52 weeks (P = 0.96). CONCLUSIONS: Repeated IAI for 52 weeks had no apparent corneal endothelial toxicity noted on specular microscopy in patients treated for neovascular age-related macular degeneration.

Reduction in Temporary and Permanent Audiological Injury Through Internal Jugular Vein Compression in a Rodent Blast Injury Model.

HYPOTHESIS: Internal jugular vein (IJV) compression influences not only intracranial but also intracochlear physiology and has demonstrated preclinical effectiveness in reducing acute audiological injury in a rodent blast model. However, the long-term effects in this model are unknown. BACKGROUND: Blast wave-induced audiological injury from an improvised explosive device is a leading cause of morbidity among service members in theater but there are limitations to the current protective measures. METHODS: For this study, we exposed 20 Sprague Dawley rats to a 16.8 ±â€Š0.3 PSI (195.3 dB SPL) right-sided shock wave in which 10 had application of a custom IJV compression collar in place at the time of injury. RESULTS: IJV compression at the time of injury was shown acutely to significantly reduce the incidence of tympanic membrane rupture and the initial temporary threshold shift on otoacoustic emissions in both the right and left ears of animals who had collar application immediately after and 7 days post injury. At 28 days from injury, collared animals demonstrated a return to baseline of otoacoustic emission values while the noncollared animals had persistent threshold shifts, signifying the presence of a permanent threshold shift only in those animals without collar application. IJV compression was also found to significantly reduce hair cell loss at the base of the cochlea secondary to mechanical trauma from the blast wind. CONCLUSION: Previously observed acute protective effects of IJV compression are sustained at chronic time points. IJV compression can potentially be used to reduce long-term permanent morbidity from blast-induced audiological trauma.

Internal Jugular Vein Compression: A Novel Approach to Mitigate Blast Induced Hearing Injury.

HYPOTHESIS: Internal jugular vein (IJV) compression before blast injury will lead to reduced risk of traumatic hearing injury following exposure to a blast injury. BACKGROUND: IJV compression and its effects on not only intracranial, but also intracochlear pressure may potentiate blast induced hearing injury, therefore, precluding its use as a prophylactic therapy for blast induced traumatic brain injury. METHODS: Twenty Sprague Dawley rats were exposed to a 17.9 ±â€Š0.4 PSI (195.8 dB SPL) right sided shock wave in which 10 had application of a custom IJV compression collar before injury. All rodents received baseline and post blast injury otoacoustic emission (OAE) and auditory brainstem response (ABR) testing followed by cochlear histology. RESULTS: IJV compression was shown to significantly reduce ABR and OAE threshold shifts in comparison to the non-intervention group by: 14.9 ±â€Š4.8 dB (right ear ABR 0.5 kHz Day 1 post blast, p = 0.01), 13.1 ±â€Š4.9 dB (right ear ABR 4 kHz Day 1 post blast, p = 0.04), 16.5 ±â€Š4.5 dB (right ear ABR click Day 1 post blast, p = 0.003), 12.1 ±â€Š4.6 dB (right ear ABR click Day 6 post blast, p = 0.04), and 14.0 ±â€Š3.2 dB (both ears OAE 3.2-10 kHz, p < 0.0001). Also, those animals with collar application had a greater number of total hair cells per mm from 70 to 100% distance from the cochlear apex following blast injury in comparison to those without intervention (blast: 211.8 ±â€Š27.5 versus blast+collar: 355.5 ±â€Š39.5 [p = 0.0002]). CONCLUSION: This study supports the use of IJV compression in a pre-clinical model as a new prophylactic mechanism to combat blast induced hearing injury.

Long-term Safety and Visual Outcome of Intravitreal Aflibercept in Neovascular Age-Related Macular Degeneration: VIEW 1 Extension Study.

PURPOSE: To assess the long-term safety and vision change in patients who received intravitreal aflibercept injection (IAI) for neovascular age-related macular degeneration in an extension study after completing VIEW 1 trial. DESIGN: Prospective, open-label, multicenter, extension study. PARTICIPANTS: Three hundred twenty-three patients. METHODS: In VIEW 1, 1217 patients were randomized to receive fixed dosing of 0.5 mg IAI every 4 weeks (0.5q4), 2 mg IAI every 4 weeks (2q4), 2 mg IAI every 8 weeks after 3 initial monthly dosing (2q8), or 0.5 mg ranibizumab every 4 weeks (Rq4) from baseline through week 52, followed by modified quarterly injections of the same dose of anti-vascular endothelial growth factor agent from weeks 52 to 96. After completing VIEW 1 at week 96, patients (n = 323) enrolled in an extension study and received 2 mg IAI on a modified quarterly injection schedule followed by at least an every 8-week dosing through week 212. MAIN OUTCOME MEASURES: Long-term safety and vision change in patients followed for a median duration of 116 weeks in the extension study (total follow-up time of 212 weeks from the VIEW 1 baseline). RESULTS: Patients enrolled in the extension study gained a mean of 10.2 letters from the VIEW 1 baseline at week 96. These patients largely maintained vision over the extension study with a mean gain of 7.1 letters from the VIEW 1 baseline to week 212. The proportion of patients who lost ≥15 letters from the VIEW 1 extension baseline was 8.2% at week 212. Mean number of injections was 12.9 (range, 1-41) in the extension study. The most common serious ocular adverse event was endophthalmitis (0.9%). The overall incidence of Antiplatelet Trialists' Collaboration-defined arterial thromboembolic events was 6.2%. CONCLUSIONS: Vision gains achieved with anti-vascular endothelial growth factor therapy in VIEW 1 were largely maintained by continued treatment with IAI 2 mg in the extension study. Anti-vascular endothelial growth factor injections (including 4 years of IAI 2 mg) were well-tolerated with no new safety signals compared with the known profile of IAI.

Intravitreal Aflibercept for Macular Edema Following Branch Retinal Vein Occlusion: 52-Week Results of the VIBRANT Study.

PURPOSE: To determine week 52 efficacy and safety outcomes in eyes with macular edema after branch retinal vein occlusion (BRVO) treated with 2 mg intravitreal aflibercept injection (IAI) compared with grid laser. DESIGN: VIBRANT was a double-masked, randomized, phase 3 trial. PARTICIPANTS: Eyes randomized and treated in VIBRANT were followed to week 52. METHODS: In the IAI group, eyes received IAI every 4 weeks through week 24 and IAI every 8 weeks through week 48 with rescue grid laser if needed at week 36. In the grid laser group, all eyes received grid laser at baseline and, if prespecified rescue criteria were met, 1 additional laser from week 12 to 20 and IAI every 8 weeks after 3 monthly doses from week 24 onward (the laser/IAI group). MAIN OUTCOME MEASURES: The primary outcome measure was percentage of eyes with improvement from baseline best-corrected visual acuity (BCVA) letter score ≥15 at week 24. All outcome measures at week 52 were exploratory, and P values are considered nominal. RESULTS: The percentage of eyes with improvement from baseline letter score ≥15 in the IAI and laser/IAI groups was 52.7% versus 26.7% (P = 0.0003) at week 24 and 57.1% versus 41.1% (P = 0.0296) at week 52. The corresponding mean change from baseline BCVA letter score was 17.0 versus 6.9 (P < 0.0001) at week 24 and 17.1 versus 12.2 (P = 0.0035) at week 52. The mean reduction from baseline central retinal thickness was 280.5 µm versus 128.0 µm (P < 0.0001) at week 24 and 283.9 µm versus 249.3 µm (P = 0.0218) at week 52. In the IAI group, 10.6% of eyes received rescue laser at week 36, and in the laser/IAI group, 80.7% received rescue IAI from week 24 to week 48. Traumatic cataract in 1 eye (1.1%) in the IAI group was the only ocular serious adverse event. CONCLUSIONS: After 6 monthly IAI, injections every 8 weeks maintained control of macular edema and visual benefits through week 52. In the laser group, rescue IAI given from week 24 onward resulted in substantial visual improvements at week 52.

Surgical Techniques at Cesarean Delivery: A U.S. Survey.

Objective To assess the frequency of surgical techniques at cesarean delivery (CD) among U.S. obstetricians. Methods Members of the American College of Obstetrician Gynecologists were randomly selected and e-mailed an online survey that assessed surgical closure techniques, demographics, and reasons. Data were analyzed using SPSS (IBM Corp., Armonk, New York, United States), descriptive statistics, and analysis of variance. Results Our response rate was 53%, and 247 surveys were analyzed. A similar number of respondents either "always or usually" versus "rarely or never" reapproximate the rectus muscles (38.4% versus 43.3%, p = 0.39), and close parietal peritoneum (42.5% versus 46.9%, p = 0.46). The most frequently used techniques were double-layer hysterotomy closure among women planning future children (73.3%) and suturing versus stapling skin (67.6%); the least frequent technique was closure of visceral peritoneum (12.2%). Surgeons who perform double-layer hysterotomy closure had fewer years in practice (15.0 versus 18.7 years, p = 0.021); surgeons who close visceral peritoneum were older (55.5 versus 46.4 years old, p < 0.001) and had more years in practice (23.8 versus 13.8 years practice; p < 0.001). Conclusion Similar numbers of obstetricians either reapproximate or leave open the rectus muscles and parietal peritoneum at CD, suggesting that wide variation in practice exists. Surgeon demographics and safety concerns play a role in some techniques.

Intravitreal aflibercept for macular edema following branch retinal vein occlusion: the 24-week results of the VIBRANT study.

PURPOSE: To compare the efficacy and safety of intravitreal aflibercept injection (IAI) with macular grid laser photocoagulation for the treatment of macular edema after branch retinal vein occlusion (BRVO). DESIGN: The VIBRANT study was a double-masked, active-controlled, randomized, phase III trial. PARTICIPANTS: Treatment-naïve eyes with macular edema after BRVO were included in the study if the occlusion occurred within 12 months and best-corrected visual acuity (BCVA) was between ≤73 and ≥24 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (20/40-20/320 Snellen equivalent). METHODS: Eyes (1 eye per patient) received either IAI 2 mg every 4 weeks (n=91) from baseline to week 20 or grid laser (n=92) at baseline with a single grid laser rescue treatment, if needed, from weeks 12 through 20. MAIN OUTCOME MEASURES: The primary outcome measure was the proportion of eyes that gained ≥15 ETDRS letters from baseline BCVA at week 24. Secondary end points included mean change from baseline BCVA and central retinal thickness (CRT) at week 24. RESULTS: The proportion of eyes that gained ≥15 ETDRS letters from baseline at week 24 was 52.7% in the IAI group compared with 26.7% in the laser group (P=0.0003). The mean improvement from baseline BCVA at week 24 was 17.0 ETDRS letters in the IAI group and 6.9 ETDRS letters in the laser group (P<0.0001). The mean reduction in CRT from baseline at week 24 was 280.5 µm in the IAI group and 128.0 µm in the laser group (P<0.0001). Traumatic cataract in an IAI patient was the only ocular serious adverse event (SAE) that occurred. There were no cases of intraocular inflammation or endophthalmitis. The incidence of nonocular SAEs was 8.8% in the IAI group and 9.8% in the laser group. One Anti-Platelet Trialists' Collaboration-defined event of nonfatal stroke (1.1%) and 1 death (1.1%) due to pneumonia occurred during the 24 weeks of the study, both in patients in the laser group. CONCLUSIONS: Monthly IAI provided significantly greater visual benefit and reduction in CRT at 24 weeks than grid laser photocoagulation in eyes with macular edema after BRVO.

Obstetricians and gynecologists' practice and opinions of expanded carrier testing and noninvasive prenatal testing.

OBJECTIVE: The objective of this study is to assess the opinions of Fellows of the American College of Obstetricians and Gynecologists on expanded carrier testing (molecular detection of >100 genetic diseases of variable severity) and noninvasive prenatal testing (NIPT). METHODS: A survey conducted between March and August 2012, assessed current use of testing, provision of genetic counseling, types of disorders that should be identified, preferences for future use, ethical aspects, and views on regulatory oversight. RESULTS: Expanded carrier testing was offered to all patients by 15% of the responders and 52.1% upon patient request. Most (67.3%) favored testing only for mutations of known significance. In this study, 79.1% supported the use of NIPT as a screen for Down syndrome for all women with 47.9% viewing NIPT as a complete substitution for invasive testing. Most supported expansion to other aneuploidies (97.5%) and severe early-onset Mendelian disorders (90.4%) but not for adult-onset disorders (29.8%) or nonmedical sex identification (15.7%). A majority (73.2%) believed that NIPT would increase pregnancy terminations for mild disease states. Respondents favored a role for professional societies in providing regulatory oversight. CONCLUSION: Rapid incorporation of new genetic technologies may be limited by the availability of genetic counseling, concerns regarding inclusion of clinically mild disorders, results of unknown significance, and costs.

Obstetricians' attitudes and beliefs regarding umbilical cord clamping.

OBJECTIVE: Although delayed umbilical cord clamping has been demonstrated to reduce the incidence of intraventricular hemorrhage and neonatal sepsis, and decrease the need for neonatal transfusions (without affecting cord pH, Apgar scores or the need for phototherapy), the extent to which this practice is being employed is unknown. We conducted a survey of US obstetricians to assess their attitudes and beliefs about cord clamping. STUDY DESIGN: Questionnaires were randomly mailed to members of the American College of Obstetricians and Gynecologists (ACOG), and the Collaborative Ambulatory Research Network (CARN). The data were analyzed using Chi-square and Student t tests. RESULTS: The response rates for the CARN and other ACOG members were 47% and 21%, respectively. Most (88%) responders reported their hospital had no umbilical cord clamping policy. The most frequent response for optimal timing of umbilical cord clamping, regardless of gestational age, was "don't know". Potential for neonatal red blood cell transfusion was the only concern cited as a reason for being somewhat or very inclined to delay umbilical cord clamping (51%). Delayed neonatal resuscitation (76%) was listed as a reason to clamp the cord immediately, despite the paucity of literature to support immediate cord clamping in this cohort. CONCLUSION: Despite substantial evidence supporting the practice of delayed cord clamping, few institutions have policies regarding this practice. Moreover, obstetricians' beliefs about the appropriate timing for umbilical cord clamping are not consistent with the evidence that demonstrates its beneficial impact on neonatal outcomes.

Hydrocortisone infusion exerts dose- and sex-dependent effects on attention to emotional stimuli.

Glucocorticoid administration has been shown to exert complex effects on cognitive and emotional processing. In the current study we investigated the effects of glucocorticoid administration on attention towards emotional words, using an Affective Go/No-go task on which healthy humans have shown an attentional bias towards positive as compared to negative words. Healthy volunteers received placebo and either low-dose (0.15mg/kg) or high-dose (0.45mg/kg) hydrocortisone intravenously during two separate visits in a double-blind, randomized design. Seventy-five minutes post-infusion, the subjects performed tests of attention (Rapid Visual Information Processing [RVIP]), spatial working memory (Spatial Span) and emotional processing (Affective Go/No-go task [AGNG]). On the attention task, performance was impaired under both hydrocortisone doses relative to placebo, though the effect on error rate was not significant after controlling for age; Spatial Span performance was unaffected by hydrocortisone administration. On the AGNG task, relative to the placebo condition the low-dose hydrocortisone infusion decreased response time to emotional words while high-dose hydrocortisone increased response time. In the females specifically, both high and low dose hydrocortisone administration attenuated the normal attentional bias toward positively valenced words. These data suggest that, in healthy women, the modulation of attention by the emotional salience of stimuli is influenced by glucocorticoid hormone concentrations.

Differential effects of emotionally versus neutrally cued autobiographical memories on performance of a subsequent cognitive task: effects of task difficulty.

Attention is a limited resource, and in order to improve processing of the attended information, competing processes must be suppressed. Although it is well established that an experimentally induced change in mood state comprises one type of competing process that can impair performance on a subsequent task, no study has investigated whether an emotionally valenced autobiographical memory (AM) also can alter performance on a subsequent task. We therefore examined the effects of AM recall on cognitive performance. Healthy participants (n = 20 per experiment) recalled AMs in response to positive, negative, and neutral cue words. Following each AM participants completed a simple perceptual task (Experiment 1) or solved moderately difficult subtraction problems (Experiment 2). In Experiment 1 participants performed less accurately following exposure to positive or negative versus neutral cue words (ps < 0.001), and also were less accurate following negative versus positive cue words (p < 0.001). In Experiment 2, in contrast, no difference in accuracy or response times reached statistical significance. Performance accuracy even trended toward being higher following exposure to negative versus neutral cue words (p = 0.08). The results of Experiment 1 suggested that recalling emotionally salient AMs reduces the attention directed toward a simple continuous performance task administered immediately following the AM task, conceivably due to persistent contemplation of the AM. The negative results of Experiment 2 suggested that the effect of AMs on attention was attenuated, however, by increasing the difficulty of the subsequent task. Our results have implications for patients with major depressive disorder (MDD), as performing cognitively demanding tasks may allow them to attenuate the impairing effects of negative rumination on cognition.

Match between cue and memory valence during autobiographical memory recall in depression.

Major depressive disorder (MDD) is associated with deficits in recalling specific autobiographical memories. The current study goal was to assess whether emotionally valenced cue words led to memories of similar emotional valence and whether this pattern differed between 12 unmedicated MDD and 14 healthy control participants. Both groups recalled autobiographical memories in response to positive, negative, and neutral cue words. Positive and neutral cues prompted recall of positive memories less often in the MDD group than in the controls. MDD participants recalled fewer specific and more categorical memories than controls; however, the proportion of specific memories didn't differ across memory valences. The MDD group had fewer specific memories in response to positive and neutral cues than the controls. These results suggest that the MDD participants may process positive stimuli differently than healthy controls and that their recall of specific autobiographical memories is impaired, regardless of the affective valence of those memories.

Are obstetrician-gynecologists satisfied with their maternal-fetal medicine consultants? A survey.

OBJECTIVE: To survey generalist obstetrician-gynecologists about their satisfaction with and patterns of referral to maternal-fetal medicine (MFM) specialists. STUDY DESIGN: A survey was sent three times to 1030 randomly selected American Congress of Obstetricians and Gynecologists members across the country, and results were tabulated. RESULTS: A total of 516 surveys (50%) were returned; 68% of respondents were satisfied (S) with available MFM services and 31% were not satisfied (Not S). S and Not S respondents were similar with respect to age, gender, years in practice, type of practice, hours worked per week, proximity to MFM specialists, number of deliveries per year, and level of nursery in their hospital. Reasons for dissatisfaction included: MFM specialist not readily available (49%), during the day (26%), at night (35%), or on weekends (36%); MFM specialist unwilling to take care of hospitalized patients (26%); or MFM specialist does only ultrasound, chorionic villus sampling, and amniocentesis (32%). Although some generalists do not consult MFM specialists frequently, the majority of both S and Not S respondents would request an MFM consult or comanagement for 26 of 38 specific maternal, fetal, and obstetric diagnoses/complications. CONCLUSION: The majority of obstetrician-gynecologists are satisfied with their MFM support. The dissatisfaction expressed by 31% of generalists might be ameliorated if individual MFM specialists increased their availability and/or broadened their scope of practice.

Selective deficit in spatial location memory in extremely low birth weight children at age six: the PETIT study.

Spatial location memory has rarely been assessed in young children due to a scarcity of developmentally appropriate tests. This study sought to compare nonverbal learning and recall in children born extremely low birth weight (ELBW; <1000 g) and less than 33 gestational weeks (GW) with term-born children at early school age using a recently developed and adapted test. We administered a modification of the Hopkins Board to 210 children at age six; 84 born ELBW (35 born < 26 GW; 49 born 26-33 GW) and 126 term-born. Six measures were obtained: naming, trials-to-criterion, errors-to-criterion, delayed item recall, delayed location recall, and percent retention. After age correction, ELBW children had worse general cognition, item naming, delayed item recall, delayed location recall, and percent retention than term-born children. Delayed item recall and percent retention performances of ELBW children remained worse after correction for general cognition. ELBW groups (< 26 GW and 26-33 GW) groups performed worse than term-born children in naming and delayed item recall with chronological age as covariate. Those born before 26 GW, but not 26-33 GW, performed worse than term-born children in delayed location recall and percent retention. Differences remained significant after controlling for gender, maternal education, and delivery type. All three groups' performance declined from final learning trial to delayed location recall, with a decline greater for less than 26 GW than term-born children. Extreme prematurity (< 26 GW) and ELBW are significant risk factors for spatial location memory deficit. The modified Hopkins Board discriminated high-risk preterm and term-born children at early school age and appears to be a useful test to measure this rarely studied cognitive capacity.

Dose-dependent effects of hydrocortisone infusion on autobiographical memory recall.

The glucocorticoid hormone cortisol has been shown to impair episodic memory performance. The present study examined the effect of two doses of hydrocortisone (synthetic cortisol) administration on autobiographical memory retrieval. Healthy volunteers (n = 66) were studied on two separate visits, during which they received placebo and either moderate-dose (0.15 mg/kg IV; n = 33) or high-dose (0.45 mg/kg IV; n = 33) hydrocortisone infusion. From 75 to 150 min post-infusion subjects performed an Autobiographical Memory Test and the California Verbal Learning Test (CVLT). The high-dose hydrocortisone administration reduced the percent of specific memories recalled (p = .04), increased the percent of categorical (nonspecific) memories recalled (p < .001), and slowed response times for categorical memories (p < .001), compared with placebo performance. Under moderate-dose hydrocortisone the autobiographical memory performance did not change significantly with respect to percent of specific or categorical memories recalled or reaction times. Performance on the CVLT was not affected by hydrocortisone. These findings suggest that cortisol affects accessibility of autobiographical memories in a dose-dependent manner. Specifically, administration of hydrocortisone at doses analogous to those achieved under severe psychosocial stress impaired the specificity and speed of retrieval of autobiographical memories.

Neuropsychological and behavioral outcomes of extremely low birth weight at age three.

Preterm (PT) birth is an established risk factor for high mortality and morbidity rates. Infants and school-aged children have been well-studied, but few have described neuropsychological and behavioral outcomes at preschool age. We compared a 2004-2006 preterm/extremely low birth weight (ELBW) cohort (PT/ELBW; N = 60) born ≤ 33 weeks gestation and <1,000 g with term-born participants (N = 90) at age 3. PT/ELBW subgroups (<26 weeks; 26-33 weeks) performed more poorly than the term-born group on verbal, nonverbal, fine motor, visual-motor, visual attention, noun fluency, early number concepts, and functional communication measures prior to age correction; PT/ELBW children born <26 weeks additionally performed more poorly on action-verb fluency. Those born 26-33 weeks had executive and adaptive deficits on parental behavioral report. Age correction significantly improved preterm scores without masking relative verbal, nonverbal, motor, and behavioral weaknesses that may require early intervention. In conclusion, subtle delays in emergent neuropsychological and behavioral functions are measurable at age 3, and neurobiological immaturity remains a prepotent influence on outcome in the preschool years. Further study should enhance our understanding of the trajectory of brain development and the limits of neuroplasticity in these highly at-risk children.

Neuromotor outcomes at school age after extremely low birth weight: early detection of subtle signs.

OBJECTIVE: Motor impairments are prevalent in children born at extremely low birth weight (ELBW; <1,000 g). Rarely studied are subtle motor deficits that indicate dysfunction or delay in neural systems critical for optimal cognitive, academic, and behavioral function. We aimed to examine quantifiable signs of subtle neuromotor dysfunction in an early school-aged ELBW cohort that coincidentally had age-appropriate cognition and design copying. METHOD: We studied 97 participants born between 1998 and 2001; 74 ELBW (6.7 years ± 0.75) compared with 23 term-born (6.6 years ± 0.29). Neuromotor outcomes were assessed using the Physical and Neurological Examination of Subtle Signs-Revised, and measures of dexterity/coordination and visual-motor integration. RESULTS: ELBW participants performed worse than term-born on design-copying and dexterity, were age-appropriate compared to normative data, and had slower timed movements and more subtle overflow movements. Those ELBW born <26 weeks performed most poorly compared with those born 26-34 weeks and term-born. CONCLUSION: Subtle motor dysfunctions are detectable and quantifiable in ELBW children by school age, even in the presence of average cognition. Early age assessment of incoordination, motor speed, and overflow movements should aid initiation of timely therapies to prepare at-risk ELBW children for subsequent school entry and facilitate design of optimal early treatment strategies.

Cognitive deficit in preschoolers born late-preterm.

BACKGROUND: late-preterm (LPT) birth accounts for a majority of preterm deliveries and until recently was considered low risk for poor cognitive outcome. Previously, we reported deficits in complicated LPT (cLPT) preschoolers (neonatal intensive care unit [NICU]-admitted). AIM: to extend our prior study by comparing cognitive outcome in cLPT and uncomplicated LPT (uLPT; NICU non-admitted) preschoolers. STUDY DESIGN: single center retrospective cohort study of 118 LPT children born in 2004-2006 at 35-36 weeks of gestation; 90 cLPT and 28 uLPT, compared with 100 term-born (≥ 37 weeks of gestation and ≥ 2500 g) participants. OUTCOME MEASURE: a well-standardized measure of general conceptual ability (GCA), the Differential Ability Scales, Second Edition. RESULTS: cLPT participants had average mean performances but significantly poorer GCA, Nonverbal Reasoning, and Spatial scores than term-born children, and higher rates of Nonverbal Reasoning and Spatial impairment; uLPT did not differ from TERM. Combined LPT males were at eightfold greater risk than term-born males for nonverbal deficit, and at sevenfold greater risk for GCA impairment than LPT females. CONCLUSIONS: finding greater risk of cognitive deficit in those NICU-admitted due to clinical instability or birth weight < 2 kg compared with non-admitted preschoolers indicates that neonatal morbidities contribute to subtle cognitive deficits detectable at young age, with male gender an additive risk factor. LPT gestational age alone is an insufficient predictor of long-term neurocognitive outcome. Further study should elucidate salient etiologies for early emerging cognitive weaknesses and suggest appropriate interventions to prepare at-risk LPT preschoolers for elementary school entry.