Efficacy of standardizing fibrinolytic therapy for parapneumonic effusion.

BACKGROUND: While chest tube placement with pleural fibrinolytic medication is the established treatment of pediatric empyema, treatment failure is reported in up to 20% of these children. OBJECTIVE: Standardizing fibrinolytic administration among interventional radiology (IR) physicians to improve patient outcomes in pediatric parapneumonic effusion. MATERIALS AND METHODS: We introduced a hospital-wide clinical pathway for parapneumonic effusion (1-2 mg tissue plasminogen activator [tPA] twice daily based on pleural US grade); we then collected prospective data for IR treatment May 2017 through February 2020. These data included demographics, co-morbidities, pediatric intensive care unit (PICU) admission, pleural US grade, culture results, daily tPA dose average, twice-daily dose days, skipped dose days, pleural therapy days, need for chest CT/a second IR procedure/surgical drainage, and length of stay. We compared the prospective data to historical controls with IR treatment from January 2013 to April 2017. RESULTS: Sixty-three children and young adults were treated after clinical pathway implementation. IR referrals increased (P = 0.02) and included higher co-morbidities (P = 0.005) and more PICU patients (P = 0.05). Mean doses per day increased from 1.5 to 1.9 (P < 0.001), twice-daily dose days increased from 38% to 79% (P < 0.001) and median pleural therapy days decreased from 3.5 days to 2.5 days (P = 0.001). No IR patients needed surgical intervention. No statistical differences were observed for gender/age/weight, US grade, need for a second IR procedure or length of stay. US grade correlated with greater positive cultures, need for chest CT/second IR procedure, and pleural therapy days. CONCLUSION: Interventional radiology physician standardization improved on a clinical pathway for fibrinolysis of parapneumonic effusion. Despite higher patient complexity, pleural therapy duration decreased. There were no chest tube failures needing surgical drainage.

Maternal Smoking and Congenital Heart Defects, National Birth Defects Prevention Study, 1997-2011.

OBJECTIVES: To assess associations between maternal smoking and congenital heart defects (CHDs) in offspring. STUDY DESIGN: We performed a retrospective case-control study using data for cases of CHD (n = 8339) and nonmalformed controls (n = 11 020) from all years (1997-2011) of the National Birth Defects Prevention Study. Maternal self-reported smoking 1 month before through 3 months after conception was evaluated as a binary (none, any) and categorical (light, medium, heavy) exposure. Multivariable logistic regression was used to estimate aOR and 95% CIs. Stratified analyses were performed for septal defects according to maternal age, prepregnancy body mass index, and maternal race/ethnicity. RESULTS: Multiple CHDs displayed modest associations with any level of maternal periconceptional smoking independent of potential confounders; the strongest associations were for aggregated septal defects (OR, 1.5; 95% CI, 1.3-1.7), tricuspid atresia (OR, 1.7; 95% CI, 1.0-2.7), and double outlet right ventricle (DORV) (OR, 1.5; 95% CI, 1.1-2.1). Tricuspid atresia and DORV also displayed dose-response relationships. Among heavy smokers, the highest odds were again observed for tricuspid atresia (aOR 3.0; 95% CI, 1.5-6.1) and DORV (aOR 1.5; 95% CI, 1.1-2.2). Heavy smokers ≥35 years old more frequently had a child with a septal defect when compared with similarly aged nonsmokers (aOR 2.3; 95% CI, 1.4-3.9). CONCLUSIONS: Maternal periconceptional smoking is most strongly associated with septal defects, tricuspid atresia, and DORV; the risk for septal defects is modified by maternal age.

Dodecafluoropentane Emulsion in Acute Ischemic Stroke: A Phase Ib/II Randomized and Controlled Dose-Escalation Trial.

PURPOSE: This randomized, placebo-controlled, double-blind, dose-escalation acute ischemic stroke trial was designed to demonstrate maximum tolerated dose, characterize adverse events (AEs), and explore clinical outcomes when intravenous dodecafluoropentane emulsion (DDFPe) was used as neuroprotection. METHODS: Acute ischemic stroke patients (n = 24) with National Institutes of Health Stroke Scale (NIHSS) score of 2-20 were randomized to either 3 doses of intravenous DDFPe or placebo, 1 every 90 minutes, starting within 12 hours of symptom onset. Doses were given without affecting standard stroke care. Each of the 3 dose cohorts included 8 patients, with 2 receiving placebo and 6 receiving DDFPe. Primary outcomes were serious adverse events (SAEs), AEs, NIHSS score, and modified Rankin Score (mRS). RESULTS: No dose-limiting toxicities were encountered, and no maximum tolerated dose was defined. One unrelated delayed death occurred in a DDFPe patient, and another occurred in the placebo group. Group SAEs and AEs were similar in incidence and severity. Early initiation of DDFPe treatment resulted in better NIHSS score response than late initiation (P = .03). Thirty- and 90-day mRS after high-dose therapy suggested clinical improvement (P = .01 and P = .03, respectively). However, the significance of differences in clinical outcomes was limited by small patient numbers and differences in stroke severity between cohorts. CONCLUSIONS: Intravenous DDFPe appears to be safe at all doses tested. Clinical improvements in NIHSS score and mRS were significant but compromised by small sample size.

Repetitive transcranial magnetic stimulation for apathy in mild cognitive impairment: A double-blind, randomized, sham-controlled, cross-over pilot study.

Apathy is a common and disabling behavioral concomitant of many neurodegenerative conditions. The presence of apathy with Mild Cognitive Impairment (MCI) is linked with heightened rates of conversion to Alzheimer's disease. Improving apathy may slow the neurodegenerative process. The objective was to establish the efficacy of repetitive transcranial magnetic stimulation (rTMS) in improving apathy in older adults with MCI. An 8-week, double-blind, randomized, sham-controlled cross-over study was conducted in nine subjects (66 ± 9 years) with apathy and MCI. Subjects were randomized to rTMS or sham treatment (5 days/week) for 2 weeks following which they underwent a 4-week treatment-free period. Subjects then crossed-over to receive the other treatment for 2 weeks. The primary (apathy (AES-C)) and secondary (cognition (3MS & MMSE), executive function (TMT-A & TMT-B), and clinical global impression (CGI)) outcomes were assessed at baseline, 2, 6, and 8 weeks. After adjusting for baseline, there was a significantly greater improvement in the AES-C with rTMS compared to sham treatment at 2 weeks. There was significantly greater improvement in 3MS, MMSE, TMT-A, and CGI-I with rTMS compared to the sham treatment. This study establishes that rTMS is efficacious in improving apathy in subjects with MCI.

Methylphenidate for Apathy in Community-Dwelling Older Veterans With Mild Alzheimer's Disease: A Double-Blind, Randomized, Placebo-Controlled Trial.

OBJECTIVE: Apathy is a common behavioral problem in Alzheimer's disease. Apathy has profound consequences, such as functional impairment, higher service utilization, higher caregiver burden, and increased mortality. The authors' objective was to study the effects of methylphenidate on apathy in Alzheimer's disease. METHOD: A 12-week, prospective, double-blind, randomized, placebo-controlled trial (methylphenidate versus placebo) was conducted in community-dwelling veterans (N=60) with mild Alzheimer's disease. The primary outcome for apathy (Apathy Evaluation Scale-Clinician) and secondary outcomes for cognition (Mini-Mental State Examination, Modified Mini-Mental State Examination), functional status (activities of daily living, instrumental activities of daily living), improvement and severity (Clinical Global Impressions Scale [CGI]), caregiver burden (Zarit Burden Scale), and depression (Cornell Scale for Depression in Dementia) were measured at baseline and at 4, 8, and 12 weeks. RESULTS: Participants were all men (77 years old, SD=8). After adjusting for baseline, the methylphenidate group had significantly greater improvement in apathy than the placebo group at 4 weeks, 8 weeks, and 12 weeks. At 12 weeks, there was also greater improvement in cognition, functional status, caregiver burden, CGI scores, and depression in the methylphenidate group compared with the placebo group. CONCLUSIONS: Methylphenidate improved apathy in a group of community-dwelling veterans with mild Alzheimer's disease. Methylphenidate also improved cognition, functional status, caregiver burden, CGI scores, and depression.

Home-Based Exercise Program Improves Balance and Fear of Falling in Community-Dwelling Older Adults with Mild Alzheimer's Disease: A Pilot Study.

BACKGROUND/OBJECTIVE: Balance problems are common in older adults with Alzheimer's disease (AD). The objective was to study the effects of a Wii-Fit interactive video-game-led physical exercise program to a walking program on measures of balance in older adults with mild AD. METHODS: A prospective randomized controlled parallel-group trial (Wii-Fit versus walking) was conducted in thirty community-dwelling older adults (73±6.2 years) with mild AD. Home-based exercises were performed under caregiver supervision for 8 weeks. Primary (Berg Balance Scale, BBS) and secondary outcomes (fear of falls and quality of life) were measured at baseline, 8 weeks (end of intervention), and 16 weeks (8-weeks post-intervention). RESULTS: At 8 weeks, there was a significantly greater improvement (average inter-group difference [95% CI]) in the Wii-Fit group compared to the walking group in BBS (4.8 [3.3-6.2], p < 0.001), after adjusting for baseline. This improvement was sustained at 16 weeks (3.5 [2.0-5.0], p < 0.001). Analyses of the secondary outcome measures indicated that there was a significantly greater improvement in the Wii-Fit group compared to walking group in Activity-specific Balance Confidence scale (6.5 [3.6-9.4], p < 0.001) and Falls Efficacy Scale (-4.8 [-7.6 to -2.0], p = 0.002) at 8 weeks. However, this effect was not sustained at 16 weeks. Quality of life improved in both groups at 8 weeks; however, there were no inter-group differences (p = 0.445). CONCLUSION: Home-based, caregiver-supervised Wii-Fit exercises improve balance and may reduce fear of falling in community-dwelling older adults with mild AD.

Efficacy of Wii-Fit on Static and Dynamic Balance in Community Dwelling Older Veterans: A Randomized Controlled Pilot Trial.

Background/Objectives. Balance problems are well-established modifiable risk factors for falls, which are common in older adults. The objective of this study was to establish the efficacy of a Wii-Fit interactive video-game-led physical exercise program to improve balance in older Veterans. Methods. A prospective randomized controlled parallel-group trial was conducted at Veterans Affairs Medical Center. Thirty community dwelling Veterans aged 68 (±6.7) years were randomized to either the exercise or control groups. The exercise group performed Wii-Fit program while the control group performed a computer-based cognitive program for 45 minutes, three days per week for 8-weeks. The primary (Berg Balance Scale (BBS)) and secondary outcomes (fear of falling, physical activity enjoyment, and quality of life) were measured at baseline, 4 weeks, and 8 weeks. Results. Of 30 randomized subjects, 27 completed all aspects of the study protocol. There were no study-related adverse events. Intent-to-treat analysis showed a significantly greater improvement in BBS in the exercise group (6.0; 95% CI, 5.1-6.9) compared to the control group (0.5; 95% CI, -0.3-1.3) at 8 weeks (average intergroup difference (95% CI), 5.5 (4.3-6.7), p < 0.001) after adjusting for baseline. Conclusion. This study establishes that the Wii-Fit exercise program is efficacious in improving balance in community dwelling older Veterans. This trial is registered with ClinicalTrials.gov Identifier NCT02190045.

Stratifying fibrinolytic dosing in pediatric parapneumonic effusion based on ultrasound grade correlation.

BACKGROUND: Complicated pleural effusion prolongs the hospital course of pneumonia. Chest tube placement with instillation of fibrinolytic medication allows efficient drain output and decreases hospital stay. OBJECTIVE: To evaluate experience with lower fibrinolytic dose for parapneumonic effusions and to assess potential dose stratification based on a simple ultrasound grading system. MATERIALS AND METHODS: We retrospectively reviewed the medical record to identify children and young adults who received fibrinolytic therapy for parapneumonic effusion and had chest tube placement by an interventional radiology service at a single children's hospital. We assessed tissue plasminogen activator (tPA) dosing and treatment duration, as well as the need for a second pleural procedure or surgical drainage. Diagnostic US images were classified as showing less than 50% pleural echogenicity (grade 1) or greater than 50% pleural echogenicity (grade 2) and were correlated with clinical parameters. RESULTS: Of 32 patients with parapneumonic effusion, all except one received at least some 1-mg tPA doses. Dosing was solely 1-mg tPA in 81% of subjects; 19% of subjects also received 2-mg tPA doses. Mean fibrinolytic duration was 3.1 days for grade 1 effusions compared to 5.4 days for grade 2 effusions. A second pleural procedure was required in 15.6% of children. Pleural drainage with fibrinolytic therapy was successful in 97%; only one child required surgical drainage. Grade 2 US differed significantly from grade 1 US, with grade 2 occurring in younger patients (P < 0.0001), smaller patients (P < 0.0001), those needing a second procedure (P = 0.001), those with positive pleural culture or polymerase chain reaction test (P = 0.006), and those with longer treatment duration (P = 0.03). CONCLUSION: A lower 1-mg dosing regimen of tissue plasminogen activator was effective in all children with less complex (grade 1 US imaging) parapneumonic effusions. Grade 2 US images correlated with younger and smaller children, presence of a pleural organism, and longer or more complicated chest tube duration.

Evaluation of an Innovative Method for Calculating Energy Intake of Hospitalized Patients.

The purpose of this study was to evaluate a multi-component method for capturing nutrient intake, which used observation, photography, and an innovative computer program. To assess reliability and accuracy, multiple responsible employees (REs) independently conducted nutrient intake assessments on simulated meals; each RE's results relating to energy intake were compared to those from the other REs and to those obtained by pre- and post-meal weighing of the food items. System efficiency was assessed by having REs perform independent assessments on the same set of simulated meals using either the new or traditional hospital method for which the REs had to document each food item served and then find the items in a computer database-steps that were automated in the new method. Interrater reliability for energy intake estimated on clinic wards was excellent (intraclass correlation coefficient = 0.975, 95% CI 0.958 to 0.992) and there was a high level of agreement between the REs' estimates and the true values determined by food weighing; per the method of Bland and Altman the mean difference between the two types of estimates was 0.3 kcal (95% CI, -8.1 to 8.7 kcal) with limits of agreement of -79.5 kcal to 80.1 kcal. Compared to the traditional method, energy intake assessments could be completed using the multi-component method in less than a third of the time. These results indicate the multi-component method is an accurate, reliable, and efficient method of obtaining energy intake assessments for hospitalized patients.

Dysapoptosis of osteoblasts and osteocytes increases cancellous bone formation but exaggerates cortical porosity with age.

Skeletal aging is accompanied by decreased cancellous bone mass and increased formation of pores within cortical bone. The latter accounts for a large portion of the increase in nonvertebral fractures after age 65 years in humans. We selectively deleted Bak and Bax, two genes essential for apoptosis, in two types of terminally differentiated bone cells: the short-lived osteoblasts that elaborate the bone matrix, and the long-lived osteocytes that are immured within the mineralized matrix and choreograph the regeneration of bone. Attenuation of apoptosis in osteoblasts increased their working lifespan and thereby cancellous bone mass in the femur. In long-lived osteocytes, however, it caused dysfunction with advancing age and greatly magnified intracortical femoral porosity associated with increased production of receptor activator of nuclear factor-κB ligand and vascular endothelial growth factor. Increasing bone mass by artificial prolongation of the inherent lifespan of short-lived osteoblasts, while exaggerating the adverse effects of aging on long-lived osteocytes, highlights the seminal role of cell age in bone homeostasis. In addition, our findings suggest that distress signals produced by old and/or dysfunctional osteocytes are the culprits of the increased intracortical porosity in old age.

FOXOs attenuate bone formation by suppressing Wnt signaling.

Wnt/ß-catenin/TCF signaling stimulates bone formation and suppresses adipogenesis. The hallmarks of skeletal involution with age, on the other hand, are decreased bone formation and increased bone marrow adiposity. These changes are associated with increased oxidative stress and decreased growth factor production, which activate members of the FOXO family of transcription factors. FOXOs in turn attenuate Wnt/ß-catenin signaling by diverting ß-catenin from TCF- to FOXO-mediated transcription. We show herein that mice lacking Foxo1, -3, and -4 in bipotential progenitors of osteoblast and adipocytes (expressing Osterix1) exhibited increased osteoblast number and high bone mass that was maintained in old age as well as decreased adiposity in the aged bone marrow. The increased bone mass in the Foxo-deficient mice was accounted for by increased proliferation of osteoprogenitor cells and bone formation resulting from upregulation of Wnt/ß-catenin signaling and cyclin D1 expression, but not changes in redox balance. Consistent with this mechanism, ß-catenin deletion in Foxo null cells abrogated both the increased cyclin D1 expression and proliferation. The elucidation of a restraining effect of FOXOs on Wnt signaling in bipotential progenitors suggests that FOXO activation by accumulation of age-associated cellular stressors may be a seminal pathogenetic mechanism in the development of involutional osteoporosis.

Strategies for developing biostatistics resources in an academic health center.

Biostatistics--the application of statistics to understanding health and biology-provides powerful tools for developing research questions, designing studies, refining measurements, analyzing data, and interpreting findings. Biostatistics plays an important role in health-related research, yet biostatistics resources are often fragmented, ad hoc, or oversubscribed within academic health centers (AHCs). Given the increasing complexity and quantity of health-related data, the emphasis on accelerating clinical and translational science, and the importance of conducting reproducible research, the need for the thoughtful development of biostatistics resources within AHCs is growing.In this article, the authors identify strategies for developing biostatistics resources in three areas: (1) recruiting and retaining biostatisticians, (2) efficiently using biostatistics resources, and (3) improving biostatistical contributions to science. AHCs should consider these three domains in building strong biostatistics resources, which they can leverage to support a broad spectrum of research. For each of the three domains, the authors describe the advantages and disadvantages of AHCs creating centralized biostatistics units rather than dispersing such resources across clinical departments or other research units. They also address the challenges that biostatisticians face in contributing to research without sacrificing their individual professional growth or the trajectory of their research teams. The authors ultimately recommend that AHCs create centralized biostatistics units because this approach offers distinct advantages both to investigators who collaborate with biostatisticians as well as to the biostatisticians themselves, and it is better suited to accomplish the research and education missions of AHCs.

Non-nuclear-initiated actions of the estrogen receptor protect cortical bone mass.

Extensive evidence has suggested that at least some of the effects of estrogens on bone are mediated via extranuclear estrogen receptor α signaling. However, definitive proof for this contention and the extent to which such effects may contribute to the overall protective effects of estrogens on bone maintenance have remained elusive. Here, we investigated the ability of a 17ß-estradiol (E2) dendrimer conjugate (EDC), incapable of stimulating nuclear-initiated actions of estrogen receptor α, to prevent the effects of ovariectomy (OVX) on the murine skeleton. We report that EDC was as potent as an equimolar dose of E2 in preventing bone loss in the cortical compartment that represents 80% of the entire skeleton, but was ineffective on cancellous bone. In contrast, E2 was effective in both compartments. Consistent with its effect on cortical bone mass, EDC partially prevented the loss of both vertebral and femoral strength. In addition, EDC, as did E2, prevented the OVX-induced increase in osteoclastogenesis, osteoblastogenesis, and oxidative stress. Nonetheless, the OVX-induced decrease in uterine weight was unaltered by EDC but was restored by E2. These results demonstrate that the protection of cortical bone mass by estrogens is mediated, at least in part, via a mechanism that is distinct from the classic mechanism of estrogen action on reproductive organs.

Three variations in rabbit angiographic stroke models.

PURPOSE: To develop angiographic models of embolic stroke in the rabbit using pre-formed clot or microspheres to model clinical situations ranging from transient ischemic events to severe ischemic stroke. MATERIALS AND METHODS: New Zealand White rabbits (N=151) received angiographic access to the internal carotid artery (ICA) from a femoral approach. Variations of emboli type and quantity of emboli were tested by injection into the ICA. These included fresh clots (1.0-mm length, 3-6h), larger aged clots (4.0-mm length, 3 days), and 2 or 3 insoluble microspheres (700-900 µm). Neurological assessment scores (NAS) were based on motor, sensory, balance, and reflex measures. Rabbits were euthanized at 4, 7, or 24h after embolization, and infarct volume was measured as a percent of total brain volume using 2,3,5-triphenyltetrazolium chloride (TTC). RESULTS: Infarct volume percent at 24 h after stroke was lower for rabbits embolized with fresh clot (0.45±0.14%), compared with aged clot (3.52±1.31%) and insoluble microspheres (3.39±1.04%). Overall NAS (including posterior vessel occlusions) were positively correlated to infarct volume percent measurements in the fresh clot (r=0.50), aged clot (r=0.65) and microsphere (r=0.62) models (p<0.001). CONCLUSION: The three basic angiographic stroke models may be similar to human transient ischemic attacks (TIA) (fresh clot), major strokes that can be thrombolysed (aged clot), or major strokes with insoluble emboli such as atheromata (microspheres). Model selection can be tailored to specific research needs.

Nutrient intake, peripheral edema, and weight change in elderly recuperative care patients.

BACKGROUND: It is unclear whether serial measures of body weight are valid indicators of nutritional status in older patients recovering from illness. Objectives. Investigate the relative influence of nutrient intake and changes in peripheral edema on weight change. METHODS: A prospective cohort study of 404 older men (mean age = 78.7±7.5 years) admitted to a transitional care unit of a Department of Veterans Affairs nursing home. Body weight and several indicators of lower extremity edema were measured at both unit admission and discharge. Complete nutrient intake assessments were performed daily. RESULTS: Over a median length of stay of 23 days (interquartile range: 15-41 days), 216 (53%) participants gained or lost more than or equal to 2.5% of their body weight. Two hundred eighty-two (70%) participants had recognizable lower extremity pitting edema at admission and/or discharge. The amount of weight change was strongly and positively correlated with multiple indicators of both nutrient intake and the change in the amount of peripheral edema. By multivariable analysis, the strongest predictor of weight change was maximal calf circumference change (partial R (2) = .35, p < .0001), followed by average daily energy intake (partial R (2) = .14, p < .0001), and the interaction of energy intake by time (partial R (2) = .02, p < .0001). CONCLUSIONS: Many older patients either gain or lose a significant amount of weight after admission to a transitional care unit. Because of the apparent high prevalence of co-occurring changes in total body water, the weight changes do not necessarily represent changes in nutritional status. Although repeat calf circumference measurements may provide some indication as to how much of the weight change is due to changes in body water, there is currently no viable alternative to monitoring the nutrient intake of older recuperative care patients in order to ensure that their nutrient needs are being met.

Changes in activities of daily living, nutrient intake, and systemic inflammation in elderly adults receiving recuperative care.

OBJECTIVES: To determine the relationships between physical function, systemic inflammation, and nutrient intake in elderly adults who are deconditioned or recovering from medical illness. DESIGN: Prospective observational study. SETTING: Recuperative care and rehabilitation setting of a Veterans Affairs hospital. PARTICIPANTS: Older adults assessed to be in need of and likely to benefit from specialized inpatient care (N = 336, aged 78.9 ± 7.5, median length of stay 24 days). MEASUREMENTS: Functional assessments and plasma analyses for albumins and inflammatory markers were performed at admission and discharge. Complete nutrient intake assessments were performed daily. Katz (independence in activities of daily living) and walking endurance (distance capability and summation of need for assistive device and human help) scores were based on direct observation and provider query. Data were analyzed using least-squares and logistic regression analyses. RESULTS: Changes in physical function between admission and discharge were positively correlated with change in nutrient intake and inversely correlated with inflammation at admission and its change. Participants in the upper quartile of change for nutrient intake (particularly improved protein intake) were two to three times as likely to experience a clinically significant change in functional status during the hospitalization. Similarly, the odds of experiencing an improvement in physical function were two to four times as great for participants whose C-reactive protein levels declined as for those whose levels increased. These relationships remained significant after controlling for age, length of stay, and other baseline indicators of health status. CONCLUSION: Protein intake and inflammation are significantly correlated with functional recovery for aging individuals undergoing recuperative care and rehabilitation. Future studies should investigate whether combined interventions that target these factors improve recovery during hospitalization for this population.

Dodecafluoropentane emulsion decreases infarct volume in a rabbit ischemic stroke model.

PURPOSE: To assess the efficacy of dodecafluoropentane emulsion (DDFPe), a nanodroplet emulsion with significant oxygen transport potential, in decreasing infarct volume in an insoluble-emboli rabbit stroke model. MATERIALS AND METHODS: New Zealand White rabbits (N = 64; weight, 5.1 ± 0.50 kg) underwent angiography and received embolic spheres in occluded internal carotid artery branches. Rabbits were randomly assigned to groups in 4-hour and 7-hour studies. Four-hour groups included control (n = 7, embolized without treatment) and DDFPe treatment 30 minutes before stroke (n = 7), at stroke onset (n = 8), and 30 minutes (n = 5), 1 hour (n = 7), 2 hours (n = 5), or 3 hours after stroke (n = 6). Seven-hour groups included control (n = 6) and DDFPe at 1 hour (n = 8) and 6 hours after stroke (n = 5). DDFPe dose was a 2% weight/volume intravenous injection (0.6 mL/kg) repeated every 90 minutes as time allowed. After euthanasia, infarct volume was determined by vital stains on brain sections. RESULTS: At 4 hours, median infarct volume decreased for all DDFPe treatment times (pretreatment, 0.30% [P = .004]; onset, 0.20% [P = .004]; 30 min, 0.35% [P = .009]; 1 h, 0.30% [P = .01]; 2 h, 0.40% [P = .009]; and 3 h, 0.25% [P = .003]) compared with controls (3.20%). At 7 hours, median infarct volume decreased with treatment at 1 hour (0.25%; P = .007) but not at 6 hours (1.4%; P = .49) compared with controls (2.2%). CONCLUSIONS: Intravenous DDFPe in an animal model decreases infarct volumes and protects brain tissue from ischemia, justifying further investigation.

Physiologic effects of retinopathy of prematurity screening examinations.

PURPOSE: Preterm infants weighing less than 1500 g routinely undergo a series of eye examinations to screen for retinopathy of prematurity (ROP). While these examinations are important for the prevention of blindness, infants may suffer adverse physiologic events during and after the examination. The procedure includes administration of mydriatic eye drops that may be absorbed systemically and physical manipulation of the eye that is accompanied by stress and pain. The purpose of the study was to monitor changes in infant health status and adverse physiologic events in the 2 days after ROP eye screening. SUBJECTS: The study used 50 preterm infants with a mean gestational age of 32 weeks, undergoing their first ROP examination in a NICU located in a university medical center. DESIGN: This pilot study used a prospective, descriptive design. METHODS: Physiologic changes and illness events were recorded before and for 2 days after the eye examination, using tools that tracked parameters of respiratory, cardiovascular, gastrointestinal, and neurological status. Data were collected directly from daily audits of medical records. McNemar's test for comparing paired proportions and the signed rank test were used for comparing significance of physiologic changes before and after the ROP eye examination. PRINCIPAL RESULTS: Apnea events increased significantly (P = .04) in the 24- to 48-hour period after the eye examination compared with apnea events before the eye examination. These results were based on 39 infants who were not receiving ventilator support. There was a significant difference in the frequency of oxygen desaturation events between infants with and without apnea (0-24 hours after examination, P < .002; 25-48 hours after examination, P < .001). There were no significant differences in heart rate, cyanosis, gastric residuals, or seizures after the eye examinations. CONCLUSIONS: The ROP examinations may be associated with increased apnea, a clinically significant problem. Nursing implications include careful monitoring of infants during and after ROP eye examinations, discharge teaching for caregivers, and continued research on nursing interventions to prevent adverse physiologic events.

Adhesion molecules, altered vasoreactivity, and brain atrophy in type 2 diabetes.

OBJECTIVE: To investigate the effects of inflammation on perfusion regulation and brain volumes in type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 147 subjects (71 diabetic and 76 nondiabetic, aged 65.2 ± 8 years) were studied using 3T anatomical and continuous arterial spin labeling magnetic resonance imaging. Analysis focused on the relationship between serum soluble vascular and intercellular adhesion molecules (sVCAM and sICAM, respectively, both markers of endothelial integrity), regional vasoreactivity, and tissue volumes. RESULTS: Diabetic subjects had greater vasoconstriction reactivity, more atrophy, depression, and slower walking. Adhesion molecules were specifically related to gray matter atrophy (P = 0.04) and altered vasoreactivity (P = 0.03) in the diabetic and control groups. Regionally, sVCAM and sICAM were linked to exaggerated vasoconstriction, blunted vasodilatation, and increased cortical atrophy in the frontal, temporal, and parietal lobes (P = 0.04-0.003). sICAM correlated with worse functionality. CONCLUSIONS: Diabetes is associated with cortical atrophy, vasoconstriction, and worse performance. Adhesion molecules, as markers of vascular health, have been indicated to contribute to altered vasoregulation and atrophy.