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Purpose To report indications for wear, visual outcomes, and complications of EyePrintPRO (EPP) scleral contact lens (SCL) use. Methods A retrospective review identified all patients fitted with this device between December 2013 and March 2018. Baseline demographics, wear indication, and contact lens history were determined. Habitual-corrected visual acuity was measured at baseline and follow-up. Adverse wear symptoms and signs, reprinting, and device cessation were tracked. Results Ninety-five eyes from 69 patients were followed for a median of 12.1 months (interquartile range 4.4-19.6). Indications for wear included vision improvement and/or ocular surface stabilization in the setting of irregular corneal shape (n = 68 eyes, 72%), ocular surface disease (n = 17, 18%), exposure keratopathy (n = 7, 7%), neurotrophic keratitis (n = 5, 5%), and extracorneal topographical abnormalities preventing noncustom lens fitting such as glaucoma drainage devices (n = 8, 8%). Median habitual-corrected visual acuity improved from 0.67 to 0.08 (P = 0.0003). One-third of eyes (33.1%) developed adverse wear symptoms. Fifteen of 95 eyes (16%) developed adverse wear signs. Device cessation occurred in 10 eyes (10.5%) and reprinting occurred in 14 eyes (14.7%) unrelated to prior lens wear or indication (P = 0.67 and 0.15, respectively). In eyes that previously failed SCLs (n = 56), 12 eyes required reprinting and 49 eyes continued use. Conclusions Indications for EPP wear include irregular corneal shape, ocular surface disease, and extracorneal topographic abnormalities. Visual acuity improves with the use of EPP. Clinicians and patients should be aware of potential adverse wear symptoms/signs and device cessation that may occur with EPP use. EPP is a viable salvage therapy in eyes that previously failed SCLs.

We previously showed that 1 month of transcutaneous electrical nerve stimulation (TENS) reduces movement-evoked pain and fatigue in women with fibromyalgia (FM). Using data from this study (Fibromyalgia Activity Study with TENS [FAST]), we performed a responder analysis to identify predictors of clinical improvement in pain and fatigue with TENS, validated these models using receiver operator characteristic, and determined number needed to treat and number needed to harm. Participants were randomly assigned to active-TENS (2-125 Hz; highest-tolerable intensity), placebo-TENS, or no-TENS for 1 month. At the end of the randomized phase, placebo-TENS and no-TENS groups received active-TENS for 1 month. The predictor model was developed using data from the randomized phase for the active-TENS group (n = 103) and validated using data from placebo-TENS and no-TENS groups after active-TENS for 1 month (n = 155). Participant characteristics, initial response to TENS for pain and fatigue, sleep, psychological factors, and function were screened for association with changes in pain or fatigue using a logistic regression model. Predictors of clinical improvement in pain were initial response to pain and widespread pain index (area under the curve was 0.80; 95% confidence interval: 0.73-0.87). Predictors of clinical improvement in fatigue were marital status, sleep impairment, and initial response to TENS (area under the curve was 0.67; 95% confidence interval: 0.58-0.75). Number needed to treat for pain and fatigue ranged between 3.3 and 5.3. Number needed to harm ranged from 20 to 100 for minor TENS-related adverse events. The response to an initial 30-minute TENS treatment predicts who responds to longer-term TENS use in women with FM, making this a clinically useful procedure. Number needed to treat and number needed to harm suggest that TENS is effective and safe for managing pain and fatigue in FM.

ObjectiveTo test the hypothesis that we will be able to detect change in motor outcome measures over time in a cohort with mutations in FKRP.MethodsIndividuals with documented FKRP mutations were evaluated annually with a battery of established motor outcome measures including limited quantitative myometry and timed function measures. Results were analyzed using random coefficient regression to determine annual change in each measure. Due to the nonlinear progression through the lifespan of the study participants, pediatric (ResultsSixty-nine participants (30 pediatric, 44 adult) with at least 2 evaluations were included. There was a small but statistically significant decline in timed motor function measures in both pediatric and adult cohorts. Genotype significantly affected rate of decline in the pediatric but not the adult cohort. Some pediatric patients who are homozygous for the c.826C>A mutation showed improving motor performance in adolescence. Performance on the 10-meter walk/run was highly correlated with other timed function tests.ConclusionsThere is a slow annual decline in motor function in adults with FKRP mutations that can be detected with standard motor outcome measures, while the results in the pediatric population were more variable and affected by genotype. Overall, these analyses provide a framework for development of future clinical trials. The dystroglycanopathies natural history study (Clinical Trial Readiness for the Dystroglycanopathies) may be found on clinicaltrials.gov (NCT00313677).

Purpose To determine whether ubiquinol improves mitochondrial function and cell viability in human donor corneal endothelial cells during hypothermic corneal tissue storage. Methods Endothelial cell Descemet membrane tissues were treated with 10 μM ubiquinol, the reduced form of the antioxidant coenzyme Q10, for 5 days in Optisol-GS storage media before assaying for mitochondrial activity using extracellular flux analysis of oxygen consumption. In addition, endothelial cell Descemet membrane tissues were analyzed for cell viability using apoptosis and necrosis assays. Control tissues from mate corneas were treated with diluent only, and comparisons were analyzed for differences. Results A total of 13 donor corneal tissues with a mean (SEM) preservation time of 11.8 days (0.4) were included for the analysis. Treatment with 10 μM ubiquinol increased spare respiratory capacity by 174% (P = 0.001), maximal respiration by 93% (P = 0.003), and proton leak by 80% (P = 0.047) compared with controls. Cells treated with ubiquinol had no significant change in cell necrosis or apoptosis. Conclusions Preliminary testing in donor corneal tissue at specified doses indicates that ubiquinol may be a useful biocompatible additive to hypothermic corneal storage media that increases corneal endothelial cell mitochondrial function. Additional investigations are indicated to further study and optimize the dose and formulation of ubiquinol for use in preserving donor corneal tissue function during hypothermic storage.

Background and Purpose— We aim to determine the potential impact on stroke thrombolysis of drip-and-ship helicopter flights and specifically of their low-frequency vibrations (LFVs). Methods— Mice with a middle cerebral artery autologous thromboembolic occlusion were randomized to receive rtPA (recombinant tissue-type plasminogen activator; or saline) 90 minutes later in 3 different settings: (1) a motion platform simulator that reproduced the LFV signature of the helicopter, (2) a standardized actual helicopter flight, and (3) a ground control. Results— Mice assigned to the LFV simulation while receiving tPA had smaller infarctions (31.6 versus 54.9 mm 3 ; P =0.007) and increased favorable neurological outcomes (86% versus 28%; P =0.0001) when compared with ground controls. Surprisingly, mice receiving tPA in the helicopter did not exhibit smaller infarctions (47.8 versus 54.9 mm 3 ; P =0.58) nor improved neurological outcomes (37% versus 28%; P =0.71). This could be due to a causative effect of the 20- to 30-Hz band, which was inadvertently attenuated during actual flights. Mice using saline showed no differences between the LFV simulator and controls with respect to infarct size (80.9 versus 95.3; P =0.81) or neurological outcomes (25% versus 11%; P =0.24), ruling out an effect of LFV alone. There were no differences in blood-brain barrier permeability between LFV simulator or helicopter, compared with controls (2.45–3.02 versus 4.82 mm 3 ; P =0.14). Conclusions— Vibration in the low-frequency range (0.5–120 Hz) is synergistic with rtPA, significantly improving the effectiveness of thrombolysis without impairing blood-brain barrier permeability. Our findings reveal LFV as a novel, safe, and simple-to-deliver intervention that could improve the outcomes of patients. Visual Overview— An online visual overview is available for this article.

Objectives Adults with chronic pancreatitis (CP) have a high risk for developing pancreatogenic diabetes mellitus (DM), but little is known regarding potential risk factors for DM in children with acute recurrent pancreatitis (ARP) or CP. We compared demographic and clinical features of children with ARP or CP, with and without DM, in the INternational Study Group of Pediatric Pancreatitis: In Search for a CuRE (INSPPIRE) registry. Methods We reviewed the INSPPIRE database for the presence or absence of physician-diagnosed DM in 397 children, excluding those with total pancreatectomy with islet autotransplantation, enrolled from August 2012 to August 2017. Patient demographics, BMI percentile, age at disease onset, disease risk factors, disease burden, and treatments were compared between children with DM (n = 24) and without DM (n = 373). Results Twenty-four children (6% of the cohort) had a diagnosis of DM. Five of 13 tested were positive for beta cell autoantibodies. The DM group was 4.2 years [95% confidence interval (CI) 3-5.4] older at first episode of acute pancreatitis, and tended to more often have hypertriglyceridemia [odds ratio (OR) 5.21 (1.33-17.05)], coexisting autoimmune disease [OR 3.94 (0.88-13.65)] or pancreatic atrophy [OR 3.64 (1.13, 11.59)]. Conclusion Pancreatic atrophy may be more common among children with DM, suggesting more advanced exocrine disease. However, data in this exploratory cohort also suggest increased autoimmunity and hypertriglyceridemia in children with DM, suggesting that risk factors for type 1 and type 2 DM, respectively may play a role in mediating DM development in children with pancreatitis.

Background: Understanding the potential effects on stroke outcome of the unique physical factors present in a helicopter ambulance flight is critical in the era of thrombectomy. However, this factor in patient care has not been adequately investigated. Methods: This was a prospective randomized blinded end-point animal study. A murine model of middle cerebral artery autologous thromboembolic occlusion (eMCAO) with rtPA reperfusion was exposed to three different settings: 1) a standardized actual helicopter flight, 2) a motion platform simulator that delivered the exact LFV signature of the helicopter, and 3) a ground control. Outcome measures included infarct size and BBB permeability on MRI, and neurological scores. Results: A total of 106 mice were analyzed. Within the rtPA group, LFV simulator mice displayed lower infarction volumes on MRI (31.6 vs. 54.9 mm 3 , p=0.007) and improved neurological scores (87 vs. 28%, p=0.0001) compared to ground control mice. By contrast, mice receiving saline did not show change in either infarction volume (80.9 vs. 95.3, p=0.8) or neurological scores (37 vs. 28%, p=0.7). No differences were seen in the actual helicopter flight group as compared with ground control. No treatment group showed any difference in permeability of the blood brain barrier, assessed by MRI. Conclusion: We found a synergistic beneficial effect of combining helicopter-like LFV and rtPA, which could provide a novel, safe, and potentially more efficacious intervention for patients with stroke. These results also suggest that non-LFV helicopter physical factors, such, as hypobaric environment, accelerations and noise, may have a negating effect on the otherwise positive effect of helicopter vibration on stroke outcomes. If so, strategies to minimize these negating factors might be expected to improve patient outcome.

Purpose To compare 3 upper eyelid retraction repair techniques and introduce novel metrics, which enhance the analysis of postoperative aesthetic outcomes. Methods Retrospective review with Image J 1.48 digital analysis of patients who underwent repair of thyroid-related upper eyelid retraction at the University of Iowa from 1996 to 2014 via 1 of 3 surgical techniques, septum-opening levator recession with Muellerectomy, modified septum-preserving levator recession with Muellerectomy, and modified septum-preserving full-thickness blepharotomy, was conducted. Photographs were obtained preoperatively, 3 to 6 months postoperatively, and at last follow up (>6 months) and evaluated by digital image analysis (denoted by "i"). Outcome measures assessed were marginal reflex distance (iMRD1), temporal-to-nasal ratio, tarsal platform show (iTPS), pupil to visible eyelid crease, brow fat span (iBFS), tarsal platform show to brow fat span ratio (iTPS:iBFS), and tarsal platform show minimizing power (iTPS-minimizing power). Results A total of 121 eyelids (28 septum-opening levator recession with Muellerectomy, 66 septum-preserving levator recession with Muellerectomy, and 27 septum-preserving full-thickness blepharotomy) from 74 patients were evaluated with a mean follow up of 24.2 months. There were no statistically significant differences between techniques in terms of iMRD1 or temporal-to-nasal ratio reduction at either time point (intertechnique p values of 0.17 to >0.99). The percentage of eyelids from subjects undergoing bilateral intervention that achieved a final iMRD1 between 2.50 mm and 4.50 mm was similar (intertechnique p value of 0.23), with no difference regarding the number of subjects demonstrating iMRD1 symmetry within 1 mm (intertechnique p value of 0.15). Though iTPS elongation was greater at 3 to 6 months with septum-opening compared with the combined septum-preserving techniques (p value of 0.04), this difference was not maintained at final follow up (p value of >0.99). There was no difference in terms of iTPS symmetry at time of final follow up (intertechnique p value of 0.69). The pupil to visible eyelid crease was unchanged in all techniques (p values >0.99). Mean changes in iBFS at final follow up were -1.27 mm, -0.44 mm, and +0.55 mm for septum-opening levator recession with Muellerectomy, septum-preserving levator recession with Muellerectomy, and septum-preserving full-thickness blepharotomy (p values of 0.01, 0.49, and >0.99, respectively). Mean iTPS:iBFS ratios at final follow up were not statistically different between techniques (intertechnique p value of 0.10) and no difference in symmetry was demonstrated (intertechnique p value of 0.47). Median values for iTPS-minimizing power were: -0.83, -0.93, and -1.01 for septum-opening levator recession with Muellerectomy, septum-preserving levator recession with Muellerectomy, and septum-preserving full-thickness blepharotomy, respectively (intertechnique p value of 0.54). Conclusions Each technique appropriately lowered the eyelid and improved contour without intertechnique variability. Septum-preserving techniques demonstrated less iTPS elongation initially, but this difference was not maintained. The visible eyelid crease height (pupil to visible eyelid crease) remained stable in all techniques, indicating that the iTPS elongation seen with each technique was secondary to reduction in iMRD1 and the iBFS reduction seen with septum-opening levator recession with Muellerectomy was due to brow descent. No intertechnique differences in the amount of iTPS elongation relative to iMRD1 reduction (i.e., the novel iTPS-minimizing power) were seen. Given that each procedure evaluated yielded similar results, technique selection may be guided by surgeon experience and preference.

Physicians often exclude patients with a model for end-stage liver disease (MELD) score ≥ 18 from a transjugular intrahepatic portosystemic shunt (TIPS) procedure due to the concern for higher risk of death. We aimed to determine if TIPS increased the risk of death in these patients. We analyzed the interaction between TIPS and MELD in 106 patients with TIPS and 79 with intractable ascites without TIPS. We performed Cox proportional hazard regression, including both TIPS and MELD as time-dependent covariates together with their interaction, to calculate the impact of TIPS on the risk of death associated with a high MELD score. We found a negative interaction between a high MELD score and a history of TIPS, with potentially important effect sizes. Patients with MELD scores ≥18 had a 51% lower incremental risk of death (lower risk than would be expected from the combined independent risks of MELD and needing/receiving TIPS) associated with TIPS than patients with MELD scores

PURPOSE To quantify changes in endothelial cell density (ECD) of donor corneal tissue in relation to the presence or absence of a medical history of diabetes mellitus diagnosis, treatment, and complications. METHODS A retrospective review was performed for all corneas collected at Iowa Lions Eye Bank between January 2012 and December 2015. For purposes of analysis, donor corneas were divided into 4 groups: nondiabetic, non-insulin-dependent diabetic, insulin-dependent diabetic without medical complications due to diabetes, and insulin-dependent diabetic with medical complications due to diabetes. ECD values (obtained through specular microscopy) and transplant suitability for endothelial transplantation (determined by the standard protocol of the eye bank) were compared among groups using linear mixed model analysis. RESULTS In total, 4185 corneas from 2112 donors were included for analysis. Insulin-dependent diabetic samples with medical complications due to diabetes (N = 231 from 119 donors) showed lower ECD values compared with nondiabetic samples (-102 cells/mm, P = 0.049) and non-insulin-dependent diabetic samples (-117 cells/mm, P = 0.031). ECD values did not differ significantly among the remaining groups. The likelihood of suitability for endothelial transplantation did not differ among all 4 groups. CONCLUSIONS Corneas from donors with insulin-dependent diabetes mellitus and medical complications resulting from the disease have lower mean ECD values compared with other donors. However, our analysis suggests that these corneas are equally likely to be included in the donor pool for corneal transplantation. Additional studies are needed to determine the mechanism(s) contributing to cell loss in donors with advanced diabetes and to assess associated endothelial cell functional impairment.

Objective:To describe the spectrum of brain MRI findings in a cohort of individuals with dystroglycanopathies (DGs) and relate MRI results to function.Methods:All available brain MRIs done for clinical indications on individuals enrolled in a DG natural history study (NCT00313677) were reviewed. Reports were reviewed when MRI was not available. MRIs were categorized as follows: (1) cortical, brainstem, and cerebellar malformations; (2) cortical and cerebellar malformations; or (3) normal. Language development was assigned to 1 of 3 categories by a speech pathologist. Maximal motor function and presence of epilepsy were determined by history or examination.Results:Twenty-five MRIs and 9 reports were reviewed. The most common MRI abnormalities were cobblestone cortex or dysgyria with an anterior-posterior gradient and cerebellar hypoplasia. Seven individuals had MRIs in group 1, 8 in group 2, and 19 in group 3. Language was impaired in 100% of those in MRI groups 1 and 2, and degree of language impairment correlated with severity of imaging. Eighty-five percent of the whole group achieved independent walking, but only 33% did in group 1. Epilepsy was present in 8% of the cohort and rose to 37% of those with an abnormal MRI.Conclusions:Developmental abnormalities of the brain such as cobblestone lissencephaly, cerebellar cysts, pontine hypoplasia, and brainstem bowing are hallmarks of DG and should prompt consideration of these diagnoses. Brain imaging in individuals with DG helps to predict outcomes, especially language development, aiding clinicians in prognostic counseling.

Purpose To compare the incidence of visually significant postoperative cystoid macular edema (CME) in pseudophakic eyes after Descemet membrane endothelial keratoplasty (DMEK) performed after recent versus remote cataract surgery. Methods A retrospective chart review was performed of all consecutive eyes that underwent DMEK without concurrent cataract surgery at the University of Iowa between October 2012 and December 2014. The DMEK procedures were classified as staged if performed between 2 weeks and 6 months after cataract surgery and solitary if performed more than 6 months after cataract surgery. Possible confounders, including a history of diabetes in the recipient, were tracked. Macular optical coherence tomography was performed to detect CME 1 month after DMEK if the best-corrected visual acuity was ≤20/30 with a clear cornea with no other reason for visual compromise. Results A total of 173 eyes from 140 patients were included in the statistical analysis. Staged DMEK was performed in 88 eyes (50.8%) and solitary DMEK in 85 eyes (49.2%). The incidence of CME was 8.0% (7 of 88 eyes) in the staged DMEK group and 7.1% (6 of 85 eyes) in the solitary DMEK group (P = 0.823). The incidence of CME did not differ significantly between the staged and solitary DMEK groups regardless of the recipient diabetic status. All cases of CME resolved within 6 months on topical therapy. Conclusions The incidence of postoperative CME after DMEK is similar in the setting of recent or remote cataract surgery.

Background: There are limited data on the baseline characteristics and clinical outcomes of patients who have recurrent hemispheric syndromes in the territory of symptomatic atherosclerotic internal carotid artery occlusion (AICAO). Methods: Baseline characteristics and clinical outcomes were compared between patients with (rHEM+) and without (rHEM-) recurrent ipsilateral hemispheric syndromes at the time of randomization into the Carotid Occlusion Surgery Study (COSS) based on local investigator clinical impression. Results: Of 195 participants who were randomized, 100 (51%) were rHEM+ (50 in each study arm) and 95 were rHEM-(48 nonsurgical, 47 surgical). Baseline characteristics between rHEM+ and rHEM- participants were similar except that rHEM+ participants were more likely to have had a previous stroke prior to entry event (59% vs 22%, p < 0.001) and to have had TIA vs stroke as the entry event (61% vs 20%, p 0.10). For the nonsurgical participants, there was no statistically significant difference in the primary endpoint for those rHEM+ vs rHEM- (26.3% vs 18.9%, p=.410) Conclusion: Patients with recurrent hemispheric stroke syndromes enrolled in the COSS trial were more likely to have had previous stroke and to have TIAs as the entry event to randomization. Given the lack of surgical treatment benefit seen in these patients, early aggressive risk factor measures should be prioritized to reduce recurrent strokes, including blood pressure control which was associated with a 70% reduction in stroke in the nonsurgical group in COSS ( Neurology 2014; 82:1027-1032).

Background The aims of this study are to characterize (1) the cadaver intubation biomechanics, including the effect of repeated intubations, and (2) the relation between intubation force and the motion of an injured cervical segment. Methods Fourteen cadavers were serially intubated using force-sensing Macintosh and Airtraq laryngoscopes in random order, with simultaneous cervical spine motion recorded with lateral fluoroscopy. Motion of the C1-C2 segment was measured in the intact and injured state (type II odontoid fracture). Injured C1-C2 motion was proportionately corrected for changes in intubation forces that occurred with repeated intubations. Results Cadaver intubation biomechanics were comparable with those of patients in all parameters other than C2-C5 extension. In cadavers, intubation force (set 2/set 1 force ratio = 0.61; 95% CI, 0.46 to 0.81; P = 0.002) and Oc-C5 extension (set 2 − set 1 difference = −6.1 degrees; 95% CI, −11.4 to −0.9; P = 0.025) decreased with repeated intubations. In cadavers, C1-C2 extension did not differ (1) between intact and injured states; or (2) in the injured state, between laryngoscopes (with and without force correction). With force correction, in the injured state, C1-C2 subluxation was greater with the Airtraq (mean difference 2.8 mm; 95% CI, 0.7 to 4.9 mm; P = 0.004). Conclusions With limitations, cadavers may be clinically relevant models of intubation biomechanics and cervical spine motion. In the setting of a type II odontoid fracture, C1-C2 motion during intubation with either the Macintosh or the Airtraq does not appear to greatly exceed physiologic values or to have a high likelihood of hyperextension or direct cord compression.

PURPOSE To evaluate factors that affect eyelid crease formation before and after frontalis suspension. DESIGN Nonrandomized, comparative, interventional case series. METHODS Sixty-three patients (125 eyes) with myogenic ptosis were included. Data collected included age, gender, previous surgeries, follow up, as well as pre- and postoperative margin reflex distance, palpebral fissure height, and levator function. Intraoperative maneuvers of incorporation of the levator aponeurosis into the skin closure, conservative fat excision, and conservative skin excision were recorded. Pre- and postoperative eyelid creases were graded by 2 masked, independent observers as "good," "fair," or "poor." RESULTS The weighted κ coefficient between the graders was 0.68 (95% CI, 0.58-0.79) preoperatively and 0.70 (95% CI, 0.61-0.79) postoperatively. Evaluating preoperative eyelid crease grades, there was no significant difference with regard to age or gender (p = 0.83 or 0.69, respectively). Eyelid crease grade correlated with margin reflex distance (p = 0.0004) and palpebral fissure height (p = 0.002). There was no significant correlation of eyelid crease with levator function (p = 0.104). After frontalis sling, intraoperative maneuvers of incorporation of the levator aponeurosis into the incision, skin preservation, and fat preservation correlated with postoperative eyelid crease (p = 0.0004, 0.059, and 0.033, respectively). CONCLUSIONS Preoperative levator function in patients with adult onset myogenic ptosis may be an inaccurate measure of true levator palpebrae strength. Reliance on levator function alone in decision making for surgical intervention in these patients may be misguided. The inclusion of the intraoperative maneuvers of incorporation of the levator aponeurosis into the skin incision and preservation of fat and skin results in a stronger eyelid crease after frontalis sling surgery.

Purpose To compare corneal graft survival using tissue from diabetic and nondiabetic donors in patients undergoing initial Descemet stripping automated endothelial keratoplasty (DSAEK) or penetrating keratoplasty (PKP). Methods A retrospective chart review of pseudophakic eyes that underwent DSAEK or PKP was performed. The primary outcome measure was graft failure. Cox proportional hazard regression and Kaplan-Meier survival analyses were used to compare diabetic versus nondiabetic donor tissue for all keratoplasty cases. Results A total of 183 eyes (136 DSAEK, 47 PKP) were included in the statistical analysis. Among 24 procedures performed using diabetic donor tissue, there were 4 cases (16.7%) of graft failure (3 DSAEK, 1 PKP), and among 159 procedures performed using nondiabetic donor tissue, there were 18 cases (11.3%) of graft failure (12 DSAEK, 6 PKP). Cox proportional hazard ratio of graft failure for all cases comparing diabetic with nondiabetic donor tissue was 1.69, but this difference was not statistically significant (95% confidence interval, 0.56-5.06; P = 0.348). There were no significant differences in Kaplan-Meier curves comparing diabetic with nondiabetic donor tissue for all cases (P = 0.380). Statistical analysis of graft failure by donor diabetes status within each procedure type was not possible because of the small number of graft failure events involving diabetic tissue. Conclusions We found similar rates of graft failure in all keratoplasty cases when comparing tissue from diabetic and nondiabetic donors, but further investigation is needed to determine whether diabetic donor tissue results in different graft failure rates after DSAEK compared with PKP.

To investigate systematically the retinal and optic disk changes in central retinal vein occlusion (CRVO) and their natural history.This study comprised 562 consecutive patients with CRVO (492 nonischemic [NI-CRVO] and 89 ischemic CRVO [I-CRVO] eyes) seen within 3 months of onset. Ophthalmic evaluation at initial and follow-up visits included recording visual acuity, visual fields, and detailed anterior segment and fundus examinations and fluorescein fundus angiography.Retinal and subinternal limiting membrane hemorrhages and optic disk edema in I-CRVO were initially more marked (P0.0001) and took longer to resolve (P0.015) than that in NI-CRVO. Initially, macular edema was more marked in I-CRVO than that in NI-CRVO (P0.0001) but did not significantly differ in resolution time (P = 0.238). Macular retinal epithelial pigment degeneration, serous macular detachment, and retinal perivenous sheathing developed at a higher rate in I-CRVO than that in NI-CRVO (P0.0001). Ischemic CRVO had more retinal venous engorgement than NI-CRVO (P = 0.003). Fluorescein fundus angiography showed significantly more fluorescein leakage, retinal capillary dilatation, capillary obliteration, and broken capillary foveal arcade (P0.0001) in I-CRVO than NI-CRVO. Resolution time of CRVO was longer for I-CRVO than NI-CRVO (P0.0001).Characteristics and natural history of fundus findings in the two types of CRVO are different.

This study evaluated the efficacy of transcutaneous electrical nerve stimulation (TENS) in reducing pain and hyperalgesia and increasing function after total knee arthroplasty (TKA). We hypothesized that participants using TENS during rehabilitation exercises would report significantly lower pain during range-of-motion (ROM) activity and fast walking but not at rest, would have less hyperalgesia, and would have better function than participants receiving placebo-TENS or standard care. We also hypothesized that change in ROM pain would differ based on psychological characteristics (trait anxiety, pain catastrophizing, and depression) and treatment group. This prospective, randomized study used intent-to-treat analyses in 317 participants after primary, unilateral TKA. Assessors, blinded to treatment allocation, measured pain, function (ROM and gait speed), and hyperalgesia (quantitative sensory tests) postoperatively and 6 weeks after surgery. Analgesic intake, anxiety, depression, and pain catastrophizing were also assessed. TENS participants used it 1 to 2 times per day at 42 mA (on average) and had less pain postoperatively during active knee extension (P=.019) and fast walking (P=.006) than standard care participants. TENS and placebo-TENS were not significantly different. TENS participants who scored low on anxiety and pain catastrophizing had a greater reduction in ROM pain at 6 weeks than those who scored high on these factors (P=.002 and P=.03). Both TENS and placebo-TENS participants had less postoperative mechanical hyperalgesia (P=.03-.01) than standard care participants. Supplementing pharmacologic analgesia with TENS during rehabilitation exercises reduces movement pain postoperatively, but a placebo influence exists and the effect is gone by 6 weeks. Patients with low anxiety and pain catastrophizing may benefit most from TENS.

The aim of this study was to evaluate preparation outcomes of tissue prepared for Descemet membrane endothelial keratoplasty (DMEK) from diabetic and nondiabetic donors.In this nonrandomized, consecutive case series, DMEK grafts were prepared from diabetic and nondiabetic donors by experienced technicians in 2 eye banks using slightly different, modified submerged manual preparation techniques to achieve "prestripped" graft tissue. Graft preparation results were analyzed retrospectively. The main outcome measure was the rate of unsuccessful (failed) DMEK graft preparations, defined as tears through the graft area that prevent tissue use.A total of 359 corneas prepared from 290 donors (114 diabetic and 245 nondiabetic) were included in the statistical analysis of graft preparation failure. There were no significant differences between diabetic and nondiabetic donor tissue characteristics with respect to donor age, death to preservation time, death to preparation time, endothelial cell density, percent hexagonality, or coefficient of variation. DMEK tissue preparation was unsuccessful in 19 (5.3%) cases. There was a significant difference in the site-adjusted rate of DMEK preparation failure between diabetic [15.3%; 95% confidence interval (CI), 9.0-25.0] and nondiabetic donors (1.9%; 95% CI, 0.8-4.8), and the corresponding site-adjusted odds ratio of DMEK graft preparation failure in diabetic donor tissue versus nondiabetic donor tissue was 9.20 (95% CI, 2.89-29.32; P = 0.001).Diabetes may be a risk factor for unsuccessful preparation of donor tissue for DMEK. We recommend caution in the use of diabetic tissue for DMEK graft preparation. Further study is needed to identify what subset of diabetic donors is at risk for unsuccessful DMEK graft preparation.

To investigate the incidence of ocular neovascularization (NV) in central and hemicentral retinal vein occlusion.The study comprised consecutive 912 (673 nonischemic and 239 ischemic) central retinal vein occlusion and 190 (147 nonischemic, 43 ischemic) hemicentral retinal vein occlusion eyes. Ophthalmic evaluation at initial and follow-up visits included recording visual acuity, visual fields, and detailed anterior segment and fundus examinations and fluorescein fundus angiography.In ischemic central retinal vein occlusion, within 6 months from time of onset, the cumulative probability of development of iris NV was 49%, angle NV 37%, NV glaucoma 29%, retinal NV 9%, and disk NV 6%. More severe peripheral retinal hemorrhages were significantly associated with iris NV (P = 0.005), angle NV (P = 0.0004), and NV glaucoma (P = 0.012). Eyes that developed disk NV had more cotton wool spots (P = 0.058) than those without. In ischemic hemicentral retinal vein occlusion, within 12 months of onset, the cumulative probability of development of retinal NV was 29%, disk NV 12%, and iris NV 12%; within 6 months of onset, angle NV was found in 10% and NV glaucoma in 5%. Anterior chamber flare was associated with anterior segment NV and may precede the development of NV. Patients who developed NV were significantly younger, and there was a greater prevalence of NV glaucoma in patients with primary open angle glaucoma.In ischemic central retinal vein occlusion, anterior segment NV is much more common than posterior segment NV, and the cumulative chance of developing anterior segment NV is maximum during the first 6 months. In ischemic hemicentral retinal vein occlusion, posterior segment NV is much more common than anterior segment NV.

Background: Previous studies have found that nonsteroidal anti-inflammatory drugs (NSAIDs) and statins may impact erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) levels in patients. The current study was performed to determine if NSAID or statin use is associated with lower ESR and CRP in patients with biopsy-proven giant cell arteritis (GCA). Methods: A retrospective cross-sectional study was conducted that included 161 patients via chart review. Charts of patients with GCA seen at the University of Iowa Hospitals and Clinics from 1960 to 2008 were reviewed. Inclusion criteria were adequate medication records, serum ESR and/or CRP on record, no prior corticosteroid use, and biopsy-positive GCA. Exclusion criteria were the presence of diseases known to elevate ESR or CRP. Main outcome measures included ESR and CRP values measured while evaluating patients for GCA but prior to receiving treatment. Results: Statin nonusers had an ESR of 85.0 mm per hour (interquartile range [IQR] = 60-110 mm per hour) and a CRP of 8.7 mg/dL (IQR = 2.7-16.2 mg/dL). Statin users had an ESR of 57.5 mm per hour (IQR = 35-85) and a CRP of 2.4 mg/dL (IQR = 0.8-15.9 mg/dL). Statin use was associated with a lower ESR (P = 0.005), while there was no significant association with a lower CRP (P = 0.127). NSAID nonusers had an ESR of 98.0 mm per hour (IQR = 64-116) and a CRP of 8.7 mg/dL (IQR = 2.1-16.2 mg/dL). NSAID users had an ESR of 75.0 mm per hour (IQR = 46-98.5 mm per hour) and CRP of 8.0 mg/dL (IQR. = 1.5-16.2 mg/dL). NSAID use was associated with a lower ESR (P = 0.004), but there was no significant association with a lower CRP (P = 0.522). Conclusion: Statin use and NSAID use were associated with a lower ESR; however, they were not associated with lower CRP values. Clinicians should be aware that statin or NSAID use is associated with lower ESR in patients with GCA, and this test may therefore have lower sensitivity and specificity for recognizing patients with GCA, and CRP may be a superior test to evaluate patients for GCA.

Background: Previous research shows that numerous child, parent, and procedural variables affect children's distress responses to procedures. Cognitive-behavioral interventions such as distraction are effective in reducing pain and distress for many children undergoing these procedures. Objectives: The purpose of this report was to examine child, parent, and procedural variables that explain child distress during a scheduled intravenous insertion when parents are distraction coaches for their children. Methods: A total of 542 children, between 4 and 10 years of age, and their parents participated. Child age, gender, diagnosis, and ethnicity were measured by questions developed for this study. Standardized instruments were used to measure child experience with procedures, temperament, ability to attend, anxiety, coping style, and pain sensitivity. Questions were developed to measure parent variables, including ethnicity, gender, previous experiences, and expectations, and procedural variables, including use of topical anesthetics and difficulty of procedure. Standardized instruments were used to measure parenting style and parent anxiety, whereas a new instrument was developed to measure parent performance of distraction. Children's distress responses were measured with the Observation Scale of Behavioral Distress-Revised (behavioral), salivary cortisol (biological), Oucher Pain Scale (self-report), and parent report of child distress (parent report). Regression methods were used for data analyses. Results: Variables explaining behavioral, child-report and parent-report measures include child age, typical coping response, and parent expectation of distress (p < .01 Level of parents' distraction coaching explained a significant portion of behavioral, biological, and parent-report distress measures (p < .05). Child impulsivity and special assistance at school also significantly explained child self-report of pain (p < .05). Additional variables explaining cortisol response were child's distress in the morning before clinic, diagnoses of attention deficit hyperactivity disorder or anxiety disorder, and timing of preparation for the clinic visit. Discussion: The findings can be used to identify children at risk for high distress during procedures. This is the first study to find a relationship between child behavioral distress and level of parent distraction coaching.

PURPOSE To evaluate the prevalence of postoperative complications and their impact on graft survival after primary adult optical penetrating keratoplasty (PKP). METHODS A retrospective review was done of consecutive cases of PKP performed between January 1, 1997, and December 31, 2001, for keratoconus, corneal edema, stromal scarring, and stromal dystrophy. RESULTS The inclusion criteria were met by 910 eyes, including 464 with keratoconus, 188 with corneal edema, 175 with stromal scarring, and 83 with stromal dystrophy. One or more complications occurred in 362 eyes (39.8%). The most common complication was endothelial rejection (17.3%), followed by glaucoma worsening (15.5%), bacterial keratitis (5.8%), persistent epithelial defects (3.4%), and wound dehiscence (1.6%). There were significant differences among the surgical groups in overall prevalence of complications (P < 0.001) and with the prevalence of endothelial rejection (P = 0.01), glaucoma worsening (P < 0.001), bacterial keratitis (P = 0.04), and persistent epithelial defects (P = 0.02). Complication-associated graft failure varied significantly among the surgical groups (P = 0.02). CONCLUSION The prevalence of post-PKP complications and their impact on graft survival vary significantly among surgical indications for primary adult optical PKP.

The study objective was to determine the concordance of intraocular pressure (IOP) in glaucoma suspects (GS) and normal tension glaucoma (NTG) patients.This was a retrospective review of diurnal curves of untreated GS and NTG patients. No subject had IOP greater than 21 mm Hg. We defined GS patients as having suspicious optic nerves with normal visual fields, and NTG patients as having glaucomatous optic nerves with associated visual field loss. Goldmann applanation tonometry was performed at 10:00, 13:00, 16:00, 19:00, 22:00, and 07:00. Linear association of OD and OS IOP was estimated using Pearson correlation coefficient (r). The diurnal period was divided into 7 time intervals of 3, 6, 9, 12, 15, 18, and 21 hours, and the absolute difference in change in IOP between fellow eyes and probability that it was within 3 mm Hg were calculated.The study included 68 GS and 95 NTG subjects. The diurnal curves of the OD and OS showed a parallel course in both groups. The average correlations (r) of OD and OS IOP over the 6 time points were 0.78 and 0.81 for GS and NTG, respectively. The mean absolute difference in IOP change between OD and OS over the 6 time intervals ranged between 1.4 and 1.9 mm Hg for GS, and 1.3 and 1.5 mm Hg for NTG subjects. The probability that this difference was within 3 mm Hg ranged between 87% and 94% for GS, and 86% and 93% for NTG subjects.The diurnal variation in IOP between the 2 eyes in GS and NTG is largely concordant in approximately 90% of the time.

To investigate systematically the ophthalmoscopic fundus findings associated with central retinal artery occlusion (CRAO).The study included 240 consecutive patients (248 eyes) with CRAO. The eyes underwent detailed fundus evaluation and stereoscopic color fundus photography at initial and follow-up visits. Patients without evidence of giant cell arteritis were advised to have carotid Doppler imaging and echocardiography to determine the source of emboli. CRAO was classified into 3 types: permanent CRAO (175 eyes), permanent CRAO with cilioretinal artery sparing (35 eyes), and transient CRAO (38 eyes). In the three types of CRAO, acute-phase and late-phase changes in the retina, optic disk, and retinal vessels were evaluated.The main findings during the initial examination in our clinic for permanent CRAO were retinal opacity in the posterior pole (58%), cherry-red spot (90%), box-carring (19%), retinal arterial attenuation (32%), and optic disk edema (22%) and pallor (39%). The most frequent findings identified at the late stage, based on survivorship curves, were optic atrophy (91%), retinal arterial attenuation (58%), cilioretinal collaterals (18%), and macular retinal pigment epithelial changes (11%). Compared with permanent CRAO, permanent CRAO with cilioretinal artery sparing was associated with a lower incidence of all macular and optic disk abnormalities. For transient CRAO, the incidence of initial findings varied greatly compared with the other types. Intraarterial emboli were observed in 20% of patients. Carotid Doppler evaluation identified carotid vascular plaques in 67% of patients tested and hemodynamically significant (50%) obstruction in 32%. Four percent of CRAOs presented with simultaneous bilateral onset.The type and incidence of fundus findings at the initial visit and in the late phase of CRAO vary by its type. This study confirms that retinal opacity is predominantly evident in the posterior retina, that optic disk findings at presentation are common, that CRAO associated with normal-appearing retinal vessels and/or optic disk is not rare, and that observation of emboli is infrequent. Clinicians should be aware of the various presentation findings during the acute and late stages of CRAO and its various types. A complete picture of CRAO is provided by combined information of our clinical and experimental studies of CRAO.

Background: Investigators seeking to understand the impact of musculoskeletal disorders commonly use validated outcome instruments to assess the effect of diseases on physical function and quality of life. However, the influence of concomitant systemic or musculoskeletal comorbidities on these scores has not been widely considered in orthopaedic research. The purpose of this study was to determine how morbidity unrelated to the ankle influences the perception of physical function and pain by patients with ankle osteoarthritis. Methods: Short Form-36 (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS) scores, Ankle Osteoarthritis Scale (AOS) pain scale scores, demographic data, and systemic and musculoskeletal comorbidities were determined prospectively for 195 patients with ankle osteoarthritis and ninety-five age and gender-matched controls. The effect of systemic and musculoskeletal comorbidities on each of the scores was determined. Results: On the average, patients with ankle osteoarthritis had a relatively normal MCS score (47 ± 13 points) and a markedly diminished PCS score (32 ± 8 points). Both of these scores averaged 50 ± 9 points in the control group. The AOS pain score averaged 61 ± 23 points in the group with ankle osteoarthritis, whereas it averaged 10 ± 15 points in the control group. We found the perception of ankle pain by patients with ankle osteoarthritis to be significantly and linearly associated with the number of other musculoskeletal problems (not related to the foot or ankle). Conclusions: The degree of physical impairment associated with ankle osteoarthritis, as measured with the SF-36, is equivalent to that reported to be associated with severely disabling medical problems including end-stage kidney disease and congestive heart failure. The perception of ankle health status as measured with a validated, patient-oriented, anatomically specific instrument is influenced by the patients' perception of their overall musculoskeletal comorbidity status. The authors of clinical studies using these instruments should adjust for concomitant musculoskeletal disease.

Low-dose thiazide-type diuretics are recommended as initial therapy for most hypertensive patients. Chlorthalidone has significantly reduced stroke and cardiovascular end points in several landmark trials; however, hydrochlorothiazide remains favored in practice. Most clinicians assume that the drugs are interchangeable, but their antihypertensive effects at lower doses have not been directly compared. We conducted a randomized, single-blinded, 8-week active treatment, crossover study comparing chlorthalidone 12.5 mg/day (force-titrated to 25 mg/day) and hydrochlorothiazide 25 mg/day (force-titrated to 50 mg/day) in untreated hypertensive patients. The main outcome, 24-hour ambulatory blood pressure (BP) monitoring, was assessed at baseline and week 8, along with standard office BP readings every 2 weeks. Thirty patients completed the first active treatment period, whereas 24 patients completed both. An order–drug–time interaction was observed with chlorthalidone; therefore, data from only the first active treatment period was considered. Week 8 ambulatory BPs indicated a greater reduction from baseline in systolic BP with chlorthalidone 25 mg/day compared with hydrochlorothiazide 50 mg/day (24-hour mean = −12.4±1.8 mm Hg versus −7.4±1.7 mm Hg; P =0.054; nighttime mean = −13.5±1.9 mm Hg versus −6.4±1.8 mm Hg; P =0.009). Office systolic BP reduction was lower at week 2 for chlorthalidone 12.5 mg/day versus hydrochlorothiazide 25 mg/day (−15.7±2.2 mm Hg versus −4.5±2.1 mm Hg; P =0.001); however, by week 8, reductions were statistically similar (−17.1±3.7 versus −10.8±3.5; P =0.84). Within recommended doses, chlorthalidone is more effective in lowering systolic BPs than hydrochlorothiazide, as evidenced by 24-hour ambulatory BPs. These differences were not apparent with office BP measurements.

Background— Induced hypothermia is recommended to improve neurological outcomes in unconscious survivors of out-of-hospital ventricular fibrillation (VF) cardiac arrest. Patients resuscitated from a VF arrest are at risk of refibrillation, but there are few data on the effects of already existing hypothermia on defibrillation and resuscitation. Methods and Results— Thirty-two swine (mean±SE weight, 23.0±0.6 kg) were divided into 4 groups: normothermia (n=8), mild hypothermia (35°C) (n=8), moderate hypothermia (33°C) (n=8), and severe hypothermia (30°C) (n=8). Hypothermia was induced by surrounding the animal with ice, and VF was electrically induced. After 8 minutes of unsupported VF (no CPR), the swine were defibrillated (biphasic waveform) with successive shocks as needed and underwent CPR until resumption of spontaneous circulation or no response (≥10 minutes). First-shock defibrillation success was higher in the moderate hypothermia group (6 of 8 hypothermia versus 1 of 8 normothermia; P =0.04). The number of shocks needed for late defibrillation (≥1 minute after initial shock) was less in all 3 hypothermia groups compared with normothermia (all P P =NS), 7 of 8 moderate hypothermia ( P =0.001), and 5 of 8 severe hypothermia ( P =0.03) animals. Coronary perfusion pressure during CPR was not different between the groups. Conclusions— When VF was induced in the setting of moderate or severe hypothermia, resuscitative measures were facilitated with significantly improved defibrillation success and resuscitation outcome. The beneficial effect of hypothermia was not due to alteration of coronary perfusion pressure, which suggests that changes in the mechanical, metabolic, or electrophysiological properties of the myocardium may be responsible.

OBJECTIVE To investigate the effect of metoclopramide on breast milk volume and duration of breastfeeding in women delivering preterm. METHODS Women who planned to breastfeed and delivered between 23 and 34 weeks of gestation were eligible to participate in this randomized, double-blind, placebo-controlled study. Women were randomized to receive 10 mg of metoclopramide or placebo 3 times a day for 10 days, starting within 96 hours of birth. Breastfeeding education was standardized for all women. Mothers recorded the volume of breast milk expressed at each pumping for 17 days. Duration of breastfeeding was measured by monthly follow-up phone calls to each subject. RESULTS Sixty-nine women were enrolled and 57 (82%) women completed the study: 28 in the metoclopramide group and 29 in the placebo group. The 2 groups were similar in age, education, ethnicity, gestational age, and marital status. There was no significant difference between breast milk volumes in the metoclopramide and placebo groups at each of the 17 days of the study (P = .26 to .98; test for mean metoclopramide effect P = .80). There was no significant difference between groups in duration of breastfeeding, with a median of 8.8 weeks, an interquartile range of 3.4 to 12.0 weeks for the metoclopramide group and a median of 8.6 weeks, and an interquartile range of 5.6 to 16.9 weeks for the placebo group (P = .09). CONCLUSION Metoclopramide did not improve breast milk volume or duration of breastfeeding in this population of women. Regardless of therapy received, breastfeeding duration in this study of preterm mothers was poor. LEVEL OF EVIDENCE I.

Previous studies have documented elevations in indices of sympathetic activity in cats and humans with interstitial cystitis (IC). To examine potential autonomic dysregulation in IC we examined the effects of a laboratory mental stress challenge on blood pressure and heart rate (HR) in patients with IC and healthy controls.A total of 14 female patients with IC and 14 age matched controls participated in a laboratory session, including a 25-minute mental stress challenge. Systolic blood pressure (SBP), diastolic blood pressure (DBP) and HR were measured at intervals before, during and following the stressor. The level of chronic stress, symptom severity and pain at voiding were assessed.Mean age was 49 years (range 32 to 66). The resting HR of patients with IC (82.02 bpm) was significantly higher than that of controls (63.31 bpm, p = 0.0001). There was also suggested evidence of elevated resting DBP in patients with IC (p = 0.07) but no significant difference in mean resting SBP. Autonomic arousal elicited by the laboratory stressor did not differ between the groups and subjects in each group perceived the task as equally stressful. Patients with IC had significantly elevated HR at each time point compared with controls (p0.0001) with an average mean difference +/- SD between the groups of 19.5 +/- 4.0 (main effect for group p0.0001). Although consistent increases in SBP and DBP were observed in patients after baseline, these differences were not significant.Patients with IC had an increased HR at baseline and throughout a laboratory mental stress challenge compared to healthy age matched women. No differences in HR or blood pressure reactivity were observed between the 2 groups.

Objective Genetic susceptibility to iron loading is an important factor in the development of iron overload in Africans. This suggests that persons of African descent may be at risk to develop iron overload with its attendant complications, but relatively little is known about hepatic iron overload among blacks. The aim of this study was to compare the prevalence, histological features, and clinical correlates of hepatic iron overload in a group of autopsied black and white veterans. Methods Hepatic iron concentrations (HIC) were determined on liver tissue from autopsies performed at the John Cochran Veterans Affairs Medical Center during the period 1993 to 1996. Clinical information was obtained from autopsy protocols. Sections from livers in which the HIC exceeded the upper limit of normal were examined histologically. Results Of 256 specimens, 99 were from blacks (39%), whereas 157 were from whites (61%). Thirty-one blacks (31%) had an elevated HIC versus 44 whites (28%) (ns). In the majority of these cases (18 blacks, 30 whites), the HIC was less than twice the upper limit of normal. Nine of 15 subjects with an HIC greater than twice the upper limit of normal and no evident cause of secondary iron overload were black. Conclusions The prevalence of mild-to-moderate hepatic iron overload was similar in this group of black and white veterans. Because of the inherent limitations of autopsy studies, prospective assessment of iron stores in healthy blacks is needed to determine more accurately the prevalence and clinical significance of iron overload in this population.

Purpose: Little attention has focused on systemic factors that may allow a state of chronic bladder inflammation to be established and maintained in interstitial cystitis cases. Abnormalities of the hypothalamic-pituitary-adrenal feedback system result in poorer regulation of the inflammatory response and are present in many chronic inflammatory and pain conditions, of which some have high co-morbidity with interstitial cystitis.Materials and Methods: A total of 48 patients with interstitial cystitis and 35 healthy, age matched controls collected 24-hour urine samples and 3 days of salivary samples at 7 to 8 a.m., 4 to 5 p.m. and 8 to 9 p.m. for cortisol analysis. In addition, they completed a concurrent symptom questionnaire. Prospective symptom diaries also were completed in the month before sampling.Results: Mean urinary or salivary cortisol did not differ in patients and controls. However, patients with interstitial cystitis and higher morning cortisol had significantly less pain and urgency, while th...

Background:The aims of this study are to characterize (1) the cadaver intubation biomechanics, including the effect of repeated intubations, and (2) the relation between intubation force and the motion of an injured cervical segment.Methods:Fourteen cadavers were serially intubated using force-sensi