Search

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.

This article compares the perception of health and beauty of patients after exenteration reconstruction with free flap, eyelid-sparing, split-thickness skin graft, or with a prosthesis. Cross-sectional evaluation was performed through a survey sent to all students enrolled at the University of Iowa Carver College of Medicine. The survey included inquiries about observer comfort, perceived patient health, difficulty of social interactions, and which patient appearance was least bothersome. Responses were scored from 0 to 4 for each method of reconstruction and an orbital prosthesis. A Friedman test was used to compare responses among each method of repair and the orbital prosthesis for each of the four questions, and if this was significant, then post-hoc pairwise comparison was performed with p values adjusted using Bonferroni's method. One hundred and thirty two students responded to the survey and 125 completed all four questions. Favorable response for all questions was highest for the orbital prosthesis and lowest for the split-thickness skin graft. Patient appearance with an orbital prosthesis had significantly higher scores compared to patient appearance with each of the other methods for all questions (p value < 0.0001). Second highest scores were for the free flap, which were higher than eyelid-sparing and significantly higher compared to split-thickness skin grafting (p value: Question 1: < 0.0001; Question 2: 0.0005; Question 3: 0.006; and Question 4: 0.019). The orbital prosthesis was the preferred post-operative appearance for the exenterated socket for each question. Free flap was the preferred appearance for reconstruction without an orbital prosthesis. Split-thickness skin graft was least preferred for all questions.

Background Late preterm birth (34-36 weeks’ gestation) is a common occurrence with potential for altered brain development. Methods This observational cohort study compared children at age 6-13 years based on the presence or absence of the historical risk factor of late preterm birth. Children completed a battery of cognitive assessments and underwent magnetic resonance imaging of the brain. Results Late preterm children (n=52) demonstrated slower processing speed (p=0.035) and scored more poorly in visual-spatial perception (p=0.032) and memory (p=0.007) than full term children (n=74). Parents of late preterm children reported more behavioral difficulty (p=0.004). There were no group differences in cognitive ability or academic achievement. Imaging revealed similar intracranial volumes but less total tissue and more cerebrospinal fluid (p=0.004) for late preterm children compared to full term children. The tissue difference was driven by differences in the cerebrum (p=0.028) and distributed across cortical (p=0.051) and subcortical tissue (p=0.047). Late preterm children had a relatively smaller thalamus (p=0.012) than full term children. Only full term children demonstrated significant decreases in cortical tissue volume (p

Carol GT Vance,1 Ruth L Chimenti,1 Dana L Dailey,1 Katherine Hadlandsmyth,2 M Bridget Zimmerman,3 Katharine M Geasland,1 Jonathan M Williams,4 Ericka N Merriwether,1,5 Li Alemo Munters,4 Barbara A Rakel,6 Leslie J Crofford,4 Kathleen A Sluka1 1Department of Physical Therapy and Rehabilitation Science, The University of Iowa Carver College of Medicine, Iowa City, IA, USA; 2Department of Anesthesia, College of Medicine, University of Iowa, Iowa City, IA, USA; 3Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, IA, USA; 4Department of Medicine/Rheumatology & Immunology, Vanderbilt University, Nashville, TN, USA; 5Department of Physical Therapy, New York University, New York, NY, USA; 6College of Nursing, University of Iowa, Iowa City, IA, USA Introduction: Transcutaneous electrical nerve stimulation (TENS) is a non-pharmacological intervention clinically used for pain relief. The importance of utilizing the adequate stimulation intensity is well documented; however, clinical methods to achieve the highest possible intensity are not established. Objectives: Our primary aim was to determine if exposure to the full range of clinical levels of stimulation, from sensory threshold to noxious, would result in higher final stimulation intensities. A secondary aim explored the association of pain, disease severity, and psychological variables with the ability to achieve higher final stimulation intensity. Methods: Women with fibromyalgia (N=143) were recruited for a dual-site randomized controlled trial – Fibromyalgia Activity Study with TENS (FAST). TENS electrodes and stimulation were applied to the lumbar area, and intensity was increased to sensory threshold (ST), then to “strong but comfortable” (SC1), then to “noxious” (N). This was followed by a reduction to the final stimulation intensity of “strong but comfortable” (SC2). We called this the Setting of Intensity of TENS (SIT) test. Results: There was a significant increase from SC1 (37.5 mA IQR: 35.6–39.0) to SC2 (39.2 mA IQR: 37.1–45.3) (p

ObjectiveThe aim of this study was to assess the impact of obesity on pediatric acute recurrent pancreatitis or chronic pancreatitis (CP).MethodsWe determined body mass index (BMI) status at enrollment in INSPPIRE (INternational Study group of Pediatric Pancreatitis: In search for a cuRE) cohort using CDC criteria for pediatric-specific BMI percentiles. We used the Cochran-Armitage test to assess trends and the Jonckheere-Terpstra test to determine associations.ResultsOf 446 subjects (acute recurrent pancreatitis, n = 241; CP, n = 205), 22 were underweight, 258 normal weight, 75 overweight, and 91 were obese. The BMI groups were similar in sex, race, and age at presentation. Hypertriglyceridemia was more common in overweight or obese. Obese children were less likely to have CP and more likely to have acute inflammation on imaging. Compared with children with normal weight, obese or overweight children were older at first acute pancreatitis episode and diagnosed with CP at an older age. Obese or overweight children were less likely to undergo medical or endoscopic treatment, develop exocrine pancreatic insufficiency, and require total pancreatectomy with islet autotransplantation. Diabetes was similar among all groups.ConclusionsObesity or overweight seems to delay the initial acute pancreatitis episode and diagnosis of CP compared with normal weight or underweight. The impact of obesity on pediatric CP progression and severity deserves further study.

Raw dark-green leafy vegetables (LVs) are excellent sources of vitamins A, C, K, folate and manganese. LV intake is reported in cups in the United States (US) and inaccurate cup weights could impact calculated nutrient composition. This project measured the cup weight of ten raw LVs purchased in Coralville, Iowa, compared them to weights reported in two US databases and the Nutrition Facts Label, and assessed changes in nutrient levels for a two-cup serving (one cup-equivalent, c-eq). Six individuals measured one package/head/bunch of each LV. Loosely/moderately packed pieces were weighed in a measuring cup to the nearest 0.1 g. Ready-to-eat produce was measured as purchased; heads/bunches were cut/torn into 2.5-cm pieces. All cup weights were significantly lower than weights previously reported (p

Purpose To investigate the effects of a multimodal intervention including a modified Paleolithic diet, nutritional supplements, stretching, strengthening exercises with electrical stimulation of trunk and lower limb muscles, meditation and massage on walking performance and balance of subjects with progressive multiple sclerosis (MS). Materials and methods Twenty subjects with mean (standard deviation) age of 51.7 (6.4) years and Expanded Disability Status Scale score of 6.2 (1) participated in a 12-month study. Assessments were completed at baseline, 3, 6, 9, and 12 months. Results The entire cohort did not show significant changes in any of the assessments over 12 months except higher speed of walking toward the 10 feet mark during timed up and go (TUG) test at 6 months compared with baseline (mean change 7.9 cm/s [95% confidence interval {CI}]: 0.3, 15.2; p=0.041). Sub-group analysis revealed that 50% subjects (n=10) showed decrease in TUG time from baseline to at least 3 of 4 time-points post-intervention and were considered as responders (TUG-Res), the remaining 10 subjects were considered as nonresponders (TUG-NRes). Over 12 months, TUG-Res showed decreased mean TUG time by 31% (95% CI: −52%, −2%), increased median Berg Balance Scale scores (42 to 47), 30% increase in mean timed 25-foot walk speed (>20% considered clinically significant) and increased speed of walk toward 10 feet mark during TUG by 11.6 cm/s (95% CI: −3.0, 25.9) associated with increases in step lengths and decrease in step duration. TUG-NRes showed deterioration in walking ability over 12 months. Comparison of TUG-Res and TUG-NRes showed no significant differences in adherence to intervention but better stride duration and longer step length at baseline for TUG-Res than for TUG-NRes (p, Video abstract

IntroductionThe significance of pancreas divisum (PD) as a risk factor for pancreatitis is controversial. We analyzed the characteristics of children with PD associated with acute recurrent or chronic pancreatitis to better understand its impact.Patients and methodsWe compared children with or without PD in the well-phenotyped INSPPIRE (INternational Study group of Pediatric Pancreatitis: In search for a cuRE) cohort. Differences were analyzed using 2-sample t test or Wilcoxon rank sum test for continuous variables, Pearson χ or Fisher exact test for categorical variables.ResultsPD was found in 52 of 359 (14.5%) subjects, a higher prevalence than the general population (∼7%). Females more commonly had PD (71% vs. 55%; P=0.02). Children with PD did not have a higher incidence of mutations in SPINK1, CFTR, CTRC compared with children with no PD. Children with PD were less likely to have PRSS1 mutations (10% vs. 34%; P

High levels of pain, significant anxiety, or depressive symptoms before surgery put patients at elevated risk for chronic pain and prolonged opioid use following surgery. The purpose of this preliminary study was to assess the efficacy of a 1-day Acceptance and Commitment Therapy (ACT) workshop in “at-risk” veterans for the prevention of chronic pain and opioid use following orthopedic surgery. In a randomized controlled trial, 88 at-risk veterans undergoing orthopedic surgery were assigned to treatment as usual (TAU; n = 44) or TAU plus a 1-day ACT workshop (n = 44). Pain levels and opioid use were assessed up to 3 months following surgery. Pain acceptance and values-based behavior were assessed at baseline and 3-month follow-up. Participants who completed the ACT workshop reached pain and opioid cessation sooner than those in TAU. Postoperative complications exhibited a moderating effect on these outcomes, such that the effects of ACT were greater in patients without complications. Increases in pain acceptance and values-based behavior, processes targeted in ACT, were related to better outcomes. These promising results merit further investigation in a larger clinical trial. Providing an intervention before surgery for at-risk veterans has the potential to change clinical practice from a focus on management of postoperative pain to prevention of chronic pain in at-risk individuals. Perspective This pilot study compared the effects of a 1-day preventive behavioral intervention (ACT) to TAU in at-risk veterans undergoing orthopedic surgery. Three months following the intervention, veterans receiving ACT exhibited quicker cessation of pain and opioid use. Focusing on preoperative pain management may help prevent chronic postsurgical pain.

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 Globally, preterm birth (PTB) and low infant birth weight (LBW) are leading causes of maternal and child morbidity and mortality. Inadequate water and sanitation access (WASH) are risk factors for PTB and LBW in low-income countries. Physical stress from carrying water and psychosocial stress from addressing sanitation needs in the open may be mechanisms underlying these associations. If so, then living in a community with strong social capital should be able to buffer the adverse effects of WASH on birth outcomes. The objective of this study is to assess the relationships between WASH access and social conditions (including harassment and social capital) on PTB and LBW outcomes among Indian women, and to test whether social conditions modified the association between WASH and birth outcomes. Methods and findings This cohort study examined the effect of pre-birth WASH and social conditions on self-reported PTB status and LBW status for 7,926 women who gave birth between 2004/2005 and 2011/2012 Waves of the India Human Development Survey. PTB and LBW occurred in 14.9% and 15.5% of women, respectively. After adjusting for maternal biological and socioeconomic conditions, PTB was associated with sharing a building/compound latrine (Odds Ratio (OR) = 1.55; 95% Confidence Interval (CI) = 1.01, 2.38) versus private latrine access, but suggested an effect in the opposite direction for sharing a community/public latrine (OR = 0.67; CI = 0.45, 1.01). Open defecation, type of drinking water source, minutes per day spent fetching water, and one-way time to a drinking water source were not associated with PTB. LBW was associated with spending more than two hours per day fetching water compared to less than two hours (OR = 1.33; CI = 1.05, 1.70) and suggested an association with open defecation (OR = 1.22; CI = 1.00, 1.48), but was not associated with other types of sanitation, type of drinking water source, or time to a drinking water source. Harassment of women and girls in the community was associated with both PTB (OR = 1.33; CI = 1.09, 1.62) and LBW (OR = 1.26; CI = 1.03, 1.54). The data also showed a possible association of local crime with LBW (OR = 1.30; CI = 1.00, 1.68). Statistically significant (p

This study investigates both the short- and long-term effects of splenectomy on platelet count. Methods Patients treated at our tertiary care center in years 2012-2016 with a history of splenectomy (assessed by corresponding ICD-9 and ICD-10 codes) were included if they had platelet count data available within the first 5 years postsplenectomy. Indication for and date of splenectomy as well as all platelet counts were extracted. Patients were sorted by splenectomy indication into ITP, clonal myeloid neoplasm, nonmyeloid malignancy, and trauma/other categories. ITP patients were divided further into responders, partial responders, and nonresponders. The 180-day time course of the platelet counts was graphed for patients who had at least five platelet counts performed 1 to 180 days after splenectomy. For each group of patients, a curve of best fit was identified, from which peak platelet count, days to peak platelet count, platelet count at stable state, and days to stable state were calculated. Additionally, average platelet counts for time intervals extending from prior to splenectomy to 5 years postsplenectomy were calculated for each group, including all counts available from any patient in that group. Results We identified 129 patients with a history of splenectomy. Median age at splenectomy was 36 years (range, 2-94) with 59 females and 70 males. Eighty patients underwent splenectomy for trauma/other, 21 for nonmyeloid malignancy, 6 for clonal myeloid neoplasm, and 22 for ITP. Among the ITP patients, 16 experienced complete response (2 with subsequent relapse), 3 were partial responders, and 3 were nonresponders. Overall, the trauma/other group showed the greatest degree of postsplenectomy thrombocytosis, rising from a preoperative platelet count of 154 K/µL to a maximum of 807 K/µL at postoperative day 15.4. In comparison, the nonmyeloid malignancy group rose from 95 K/µL in the week presplenectomy to a maximum of 345 K/µL at day 23.7. The trauma/other group also reached stable state more quickly (day 21.4 vs 38.0) and at a higher stable platelet count (586 K/µL vs 240 K/µL) than the nonmyeloid neoplasm group. By 1 to 5 years postsplenectomy, 95% of patients in our analysis had platelet counts within the standard normal range of 150 to 450 K/µL, albeit trauma/other and ITP responder patients had platelet counts toward the upper end of the normal range. Comparing ITP responders to partial responders, both groups showed a relative increase from baseline platelet count by days 22 to 29. Both groups also reached a stable platelet count by >5 years postsplenectomy with responders averaging 263 K/µL vs partial responders at 88 K/µL. Conclusions Our results support the well-known phenomenon of postsplenectomy thrombocytosis and illustrate the difference in platelet count response by surgical indication. Furthermore, our results suggest that postsplenectomy patients should be considered to have a different “normal range” for platelet count than nonsplenectomized patients.

Objective:To describe the phenomenon of acute illness-associated weakness (AIAW) in patients with dystroglycanopathy (DG), determine the frequency of this phenomenon in DGs, and compare it to the frequency in Duchenne-Becker muscular dystrophy (DBMD).Methods:Patients enrolled in a DG natural history study provided medical history, including major illnesses or hospitalizations, at enrollment and annually. We noted a recurring syndrome of profound transient weakness in the setting of febrile illness. To determine the frequency of this phenomenon in the DG cohort and compare it to a cohort with another membrane-related muscular dystrophy, DBMD, we surveyed patients (e-survey tool), collecting demographics and information about episodes of sudden progression of weakness and events surrounding the episodes.Results:Surveys were completed by 52 (56.6%) patients with DG and 51 (27.3%) patients with DBMD. AIAW was reported in 12 (23%) patients with DG and 2 (4%) patients with DBMD (odds ratio 7.35; 95% confidence interval 1.55, 34.77; p = 0.005). Altogether (history or survey), 21 patients with DG, with mutations in FKRP, FKTN, POMT1, POMT2, or POMGNT1, reported AIAW. These events typically occurred in children Conclusions:People with DG, across genotypes, can experience acute, transient weakness associated with a febrile illness, a phenomenon that rarely occurs in DBMD. The physiologic basis of this phenomenon is unknown.Clinicaltrials.gov identifier:NCT00313677.

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.

Opioids are the cornerstone of pain treatment in burn patients. Undertreatment of pain has been associated with psychological sequela. However, prescription opioids have been increasingly associated with adverse drug effects. Safe opioid prescribing practices have been established in other populations. The purpose of this study was to explore postdischarge prescribing practices in a regional burn center. A retrospective review of hospital and discharge records of patients ≥18 years admitted to the burn center from December 2009 to June 2012 was performed. Charts were reviewed for demographic, burn, hospital treatment, and follow-up data. Pain scores and opioid needs were assessed 24 and 48 hours before discharge. Discharge opioid prescriptions and opioid refills were recorded. Pearson correlation and multiple linear regression was used to assess variables related to discharge opioid amounts. Jonckheere-Terpstra nonparametric test was used to identify the variables associated with the number of refills of opioid analgesia. Of the 140 patients, 120 (85.7%) were discharged on opioids. The median daily prescribed amount was 114 (interquartile range, 90-180) mg morphine equivalents (ME) for a median total duration of 6 (interquartile range: 4-10) days. Age (P < .0001), male sex (P = .024), and total mg ME before discharge (P < .0001) were independently associated with the amount of opioids prescribed at discharge. The number of refills was significantly associated with the average pain within 48 hours before discharge (P = .005) and with 24 hour predischarge mg ME (P = .006). By 14 days, 114 (84.3%) patients were still being seen in clinic and 127 (90.0%) were no longer taking opioids. The treatment of burn pain requires large amounts of opioids. Continued opioid therapy is necessary as the patients transition to the out-patient setting. This study identified several areas that could be modified to align with safer opioid prescribing practices, including lowering daily amount of prescribed opioids, prescribing only short-acting opioids, and providing patient opioid education. Future studies should focus on the adverse effects of opioid use in burn patients.

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.

Objectives Although the majority of patients undergoing total knee arthroplasty (TKA) report substantial improvement in pain and function, a significant subset experience persistent postsurgical pain and dysfunction. Better understanding of the longitudinal postoperative course is needed, including the association between patient status following physical rehabilitation at 6-weeks post-TKA, to 6-months outcomes. This study aims to described the postoperative course of TKA and examine variables associated with change in pain and functioning between 6-weeks and 6-months post-TKA. Methods In this longitudinal study of 223 participants, assessments of analgesic intake, depression, anxiety, pain catastrophizing, dysfunction, resting and range of motion pain, and pain sensitivity were completed at 6-weeks post-TKA. Analgesic intake, pain ratings, and dysfunction data were also collected at 6-months post-TKA. Pain and dysfunction ratings were divided into none-mild and moderate-severe categories. Results Between 6-weeks and 6-months post-TKA, 75% of the sample stayed in the same pain category, 20% improved, and 5% worsened. In terms of functional changes between 6 weeks and 6 months, 65% of the sample stayed in the same functional category, whereas 31% improved and 5% worsened. Discussion These findings demonstrate that the majority of patients' pain and functioning remains stable between 6 weeks and 6 months post-TKA. However, a notable subset continues to improve or worsen in pain and functioning and the current study identifies variables associated with these changes.

ObjectiveThe aim of this study was to characterize utilization and benefit of therapeutic endoscopic retrograde cholangiopancreatography (ERCP) in children with acute recurrent pancreatitis (ARP) or chronic pancreatitis (CP).MethodsFrom August 2012 to February 2015, 301 children with ARP or CP were enrolled in the INSPPIRE (INternational Study group of Pediatric Pancreatitis: In search for a cuRE) study. Physicians reported utilization and benefit of therapeutic ERCP at enrollment. Differences were analyzed using appropriate statistical methods.ResultsOne hundred seventeen children (38.9%) underwent at least 1 therapeutic ERCP. The procedure was more commonly performed in children with CP compared with those with ARP (65.8% vs 13.5%, P < 0.0001). Utility of therapeutic ERCP was reported to be similar between ARP and CP (53% vs 56%, P = 0.81) and was found to be helpful for at least 1 indication in both groups (53/99 patients [53.5%]). Predictors for undergoing therapeutic ERCP were presence of obstructive factors in ARP and CP, Hispanic ethnicity, or white race in CP.ConclusionsTherapeutic ERCP is frequently utilized in children with ARP or CP and may offer benefit in selected cases, specifically if ductal obstruction is present. Longitudinal studies are needed to clarify the efficacy of therapeutic ERCP and to explore subgroups that might have increased benefit from such intervention.

Study question Do live birth rates (LBRs) differ between fresh embryo transfer (fresh ET) cycles and their subsequent paired frozen ET (FET) cycles, when comparing cycles based on the total FSH dose used during the fresh cycle? Summary answer When compared to the paired frozen embryo transfer cycles, the LBR in the fresh cycle of the highest total FSH dose group (>2500 IU) was reduced by 38%. What is known already There may be a negative association with high gonadotropin doses and LBR after fresh ET. It is unknown whether a similar effect is seen in FET cycles, which are done with increasing frequency. Study design, size, duration In this retrospective observational paired study, we studied IVF cycles between 10 January 2005 and 19 September 2015, for all patients who underwent a fresh, autologous IVF cycle that resulted in at least one fresh ET and at least one FET. Participants/materials, setting, methods The study included 862 women, treated in our academic medical centre, who underwent 935 fresh ET and 1274 FET cycles. Cycles were allocated into three groups based on the total gonadotropin dose they received during their fresh IVF cycle: Group 1 (≤1800 IU FSH), Group 2 (1801-2500 IU), Group 3 (>2500 IU). The primary outcome was LBR after fresh ET and its subsequent paired FET(s), as well as LBR among fresh ETs and FETs as independent samples, based on the total FSH dose used. Implantation rates obtained from fresh and FET cycles were also compared. Main results and the role of chance The unadjusted fresh LBR was similar between Groups 1 and 2 (46.0% [95% CI: 40.4-51.6] versus 43.8% [38.3-49.4], respectively) but significantly lower in Group 3 (34.4% [29.5-39.8]). The unadjusted frozen transfer LBR was similar among all groups (51.4% [46.7-56.1] versus 46.3% [41.3-51.4] versus 47.5% [42.5-52.4], respectively). When logistic regression analysis with generalized estimating equations was used to control for confounders, the adjusted LBR was found to be similar between the groups both for fresh (odds ratio [OR] = 0.97 [95% CI: 0.61-1.56] Group 2 versus Group 1, OR = 0.69 [0.39-1.21] Group 3 versus Group 1) and FET cycles (OR = 0.87 [0.58-1.31] Group 2 versus Group 1, OR = 0.95 [0.58-1.55] Group 3 versus Group 1). However, for Group 3, the adjusted fresh LBR was 38% lower than its subsequent frozen transfer LBR (OR = 0.62 [0.41-0.93]); this was a statistically significant difference, which was not observed in Group 1 (OR = 0.85 [0.56-1.27]) or Group 2 (OR = 0.95 [0.64-1.41]). Limitations, reasons for caution This study is a retrospective cohort, with all of the associated inherent biases. Wider implications of the findings Fresh LBR is negatively impacted by a high dose of total FSH used, as compared to the LBR in subsequent paired FET cycles. Frozen transfer LBR seems unaffected by the total FSH dose used in the fresh cycle, suggesting that the endometrium may be adversely affected, probably indirectly, by high dose gonadotropin use in the fresh IVF cycle only. Study funding/competing interest(s) No funding source was used for the completion of this project. There are no conflicts of interest.

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.

Previous studies have linked oxidative stress and nephrolithiasis. Animal studies have demonstrated that pomegranate juice may play a role in preventing stone formation. We examined differences between recurrent stone formers (RSFs) and non-stone formers (NSFs) regarding oxidative stress and the effect of pomegranate administration on risk factors for nephrolithiasis. RSFs were recruited prospectively and matched to a group of NSFs. Subjects submitted urine and blood samples prior to and after receiving pomegranate polyphenol extract (1,000 mg) for 90 days. Serum and urine samples were analyzed for stone risk and oxidative stress. Thirty subjects completed the study. RSFs had significantly higher levels of oxidative stress at baseline as measured by urinary 8-hydroxy-deoxyguanosine (p0.0001), 2.2'-azobis (2-amidinopropane) hydrochloride-induced serum lipid peroxidation [increased levels of lipid peroxides (p = 0.0002), and thiobarbituric acid reactive substances (p = 0.002)], but not by serum paraoxonase1 (PON1) arylesterase activity (p0.99), or by highly sensitive C-reactive protein (p0.99). Following pomegranate supplementation, there was a 10 % increase in PON1 activity in RSFs (p = 0.007), which correlated with a trend toward decreasing values of supersaturation of calcium oxalate (SSCaOx; p = 0.05). RSFs have markedly higher levels of oxidative stress than NSFs. While the ability to prevent stone formation through supplementation cannot be determined in this pilot study, supplementation with pomegranate extract does not increase the risk of stones and may confer some benefit in lowering SSCaOX in those patients with increased PON-1 levels following supplementation, confirming findings of previous animal models.

The objective of this study was to optimize a reproducible impedance spectroscopy method in elderly subjects as a means to evaluate the effects of microneedles on aging skin.Human volunteers were treated with microneedles at six sites on the upper arm. Repeated impedance measurements were taken pre- and post-microneedle insertion. Two electrode types were evaluated (dry vs. gel), using either light or direct pressure to maintain contact between the electrode and skin surface. Transepidermal water loss (TEWL) was measured as a complementary technique.Five control subjects and nine elderly subjects completed the study. Microneedle insertion produced a significant decrease in impedance from baseline in all subjects (p 0.05, regardless of electrode type or pressure application), confirming micropore formation. This was supported by a complementary significant increase in TEWL (p 0.05). The gel*direct condition produced the lowest variability between measurements, as demonstrated by a coefficient of variation of 3.8% and 3.5% (control and elderly subjects, respectively). This was lower than variation between TEWL measurements at the same sites: 19.8% and 21.6% (control and elderly subjects, respectively).Impedance spectroscopy reproducibly measures micropore formation in elderly subjects, which will be essential for future studies describing microneedle-assisted transdermal delivery in aging populations.

Multiple sclerosis is an autoimmune disease influenced by environmental factors.The feasibility of a multimodal intervention and its effect on perceived fatigue in patients with secondary progressive multiple sclerosis were assessed.This was a single-arm, open-label intervention study in an outpatient setting.A multimodal intervention including a modified paleolithic diet with supplements, stretching, strengthening exercises with electrical stimulation of trunk and lower limb muscles, meditation, and massage was used.Adherence to each component of the intervention was calculated using daily logs. Side-effects were assessed from a monthly questionnaire and blood analyses. Fatigue was assessed using the Fatigue Severity Scale (FSS). Data were collected at baseline and months 1, 2, 3, 6, 9, and 12.Ten (10) of 13 subjects who were enrolled in a 2-week run-in phase were eligible to continue in the 12-month main study. Of those 10 subjects, 8 completed the study and 6 subjects fully adhered to the study intervention for 12 months. Over a 12-month period, average adherence to diet exceeded 90% of days, and to exercise/muscle stimulation exceeded 75% of days. Nutritional supplements intake varied among and within subjects. Group daily average duration of meditation was 13.3 minutes and of massage was 7.2 minutes. No adverse side-effects were reported. Group average FSS scores decreased from 5.7 at baseline to 3.32 (p=0.0008) at 12 months.In this small, uncontrolled pilot study, there was a significant improvement in fatigue in those who completed the study. Given the small sample size and completer rate, further evaluation of this multimodal therapy is warranted.

OBJECTIVE Physical activity (PA) provides many benefits to adolescents with type 1 diabetes; however, these individuals tend to have lower fitness and PA levels than their disease-free counterparts. The purpose of this study was to examine the acute temporal associations between moderate-to-vigorous intensity PA (MVPA) and hypoglycemia (continuous glucose monitor [CGM] reading ≤70 mg/dL). RESEARCH DESIGN AND METHODS Nineteen participants (53% females) 14–20 years old with type 1 diabetes were recruited. Participant fitness was evaluated via indirect calorimetry using a maximal exercise test; body composition was measured using air displacement plethysmography. An accelerometer was worn continuously (3–5 days) and acceleration data used to estimate MVPA (minutes per day). Blood glucose values were simultaneously tracked using CGM. Controlling for sex, percent body fat (%BF), fitness, and concurrent MVPA, the likelihood of nighttime and next-day hypoglycemia due to MVPA was examined using logistic regression. RESULTS Participants were of average fitness (females: 43.9 mL/kg/min; males: 49.8 mL/kg/min) and adiposity (females: 26.2%; males: 19.2%); 63.2% met the U.S. federal guideline of accumulating 60 min/day of MVPA. Hypoglycemia was 31% more likely in those who accumulated 30 min/day more MVPA in the previous afternoon than those with less (95% CI 1.05–1.63; P = 0.017). CONCLUSIONS The results suggest that participating in afternoon MVPA increases the risk of overnight and next-day hypoglycemia, independent of sex, %BF, fitness, and concurrent MVPA. While promoting PA as a healthy behavior, it is important to educate adolescents with type 1 diabetes on prevention of hypoglycemia following PA.

Objectives/Hypothesis To develop a growth model of the minimum cross-sectional area of the normal pediatric trachea with measurements from magnetic resonance images (MRIs) to supplement the clinical criteria used to determine if a child with tracheal stenosis needs surgery. Study Design Retrospective imaging review. Methods A total of 81 patients were imaged for a variety of clinical reasons and declared to have normal tracheas fully visible in their T1 magnetic resonance image. Regression analysis was used to identify any contribution that age, gender, and z scores for height and weight have in predicting the minimum cross-sectional area of the trachea. Results The best-fit model for minimum cross-sectional area is: Area = −0.00451*age4 + 0.177*age3− 2.05*age2 + 12.6*age + 8.02 (area in mm2 and age in years). Gender and z scores for height and weight did not provide any additional explanation of variance in tracheal size. Conclusions Our study demonstrates the potential to create a growth model of the normal trachea based on cross-sectional area of the trachea using MRIs. Even with the relatively small number of patients used to build it, the model has demonstrated some ability to be used as an objective prediction tool when deciding a treatment path for a patient. With continued development of precise, objective measures to diagnose the severity of the tracheal stenosis, more patients can be given early and accurate prognosis and be treated appropriately. Level of Evidence 4. Laryngoscope, 124:1947–1951, 2014

To evaluate if slow tenaculum placement at the time of office transcervical procedures was less painful for patients than fast tenaculum placement.

Data on the effects of inhaled corticosteroid (ICS) on linear growth in children

Study of the pathophysiology and treatment of anemia of prematurity is facilitated by direct measurement of red cell volume (RCV) utilizing microliter quantities of blood samples. Our objective was to compare concurrent measurements of multiple direct RCV methods in infants.Eighteen preterm infants receiving clinically indicated transfusions had concurrent flow cytometric determinations of RCV and 24-h red blood cell (RBC) recovery based on donor-recipient differences of biotin-labeled RBCs (BioRBCs), Kidd antigen mismatched RBCs, and fetal hemoglobin-positive (HbF(+)) RBCs. High-performance liquid chromatography (HPLC) was also used for measuring HbF and adult hemoglobin protein concentrations for the determination of RCV.Concurrent RCV measurements using BioRBCs (18 and 54 µg/ml), Kidd antigen, and HbF flow cytometry were not statistically different compared with RCVs measured using the reference BioRBC density (6 µg/ml). By contrast, the HbF-HPLC method overestimated RCV by 45% compared with the reference method. All the methods demonstrated 100% 24-h posttransfusion RBC recovery (PTR24).Because BioRBC, Kidd antigen, and fetal hemoglobin (HbF) flow cytometry are safe and accurate methods requiring10 µl of patient blood for determining RCV and PTR24 in preterm infants, they can be useful in clinical and research studies of anemia and other conditions.

ADAR2 transgenic mice misexpressing the RNA editing enzyme ADAR2 (Adenosine Deaminase that act on RNA) show characteristics of overeating and experience adult onset obesity. Behavioral patterns and brain changes related to a possible addictive overeating in these transgenic mice were explored as transgenic mice display chronic hyperphagia. ADAR2 transgenic mice were assessed in their food preference and motivation to overeat in a competing reward environment with ad lib access to a running wheel and food. Metabolic activity of brain and peripheral tissue were assessed with [(18) F] fluorodeoxyglucose positron emission tomography (FDG-PET) and RNA expression of feeding related genes, ADAR2, dopamine and opiate receptors from the hypothalamus and striatum were examined. The results indicate that ADAR2 transgenic mice exhibit, (1) a food preference for diets with higher fat content, (2) significantly increased food intake that is non-distractible in a competing reward environment, (3) significantly increased messenger RNA (mRNA) expressions of ADAR2, serotonin 2C receptor (5HT2C R), D1, D2 and mu opioid receptors and no change in corticotropin-releasing hormone mRNAs and significantly reduced ADAR2 protein expression in the hypothalamus, (4) significantly increased D1 receptor and altered bioamines with no change in ADAR2, mu opioid and D2 receptor mRNA expression in the striatum and (5) significantly greater glucose metabolism in the hypothalamus, brain stem, right hippocampus, left and right mid brain regions and suprascapular peripheral tissue than controls. These results suggest that highly motivated and goal-oriented overeating behaviors of ADAR2 transgenic mice are associated with altered feeding, reward-related mRNAs and hyperactive brain mesolimbic region.

Chronic Obstructive Pulmonary Disease is the third leading cause of death in the US, and is associated with periodic exacerbations, which account for the largest proportion of health care utilization, and lead to significant morbidity, mortality, and worsening lung function. A subset of patients with COPD have frequent exacerbations, occurring 2 or more times per year. Despite many interventions to reduce COPD exacerbations, there is a significant lack of knowledge in regards to their mechanisms and predisposing factors. We describe here an important observation that defines antibody deficiency as a potential risk factor for frequent COPD exacerbations. We report a case series of patients who have frequent COPD exacerbations, and who were found to have an underlying primary antibody deficiency syndrome. We also report on the outcome of COPD exacerbations following treatment in a subset with of these patients with antibody deficiency. We identified patients with COPD who had 2 or more moderate to severe exacerbations per year; immune evaluation including serum immunoglobulin levels and pneumococcal IgG titers was performed. Patients diagnosed with an antibody deficiency syndrome were treated with either immunoglobulin replacement therapy or prophylactic antibiotics, and their COPD exacerbations were monitored over time. A total of 42 patients were identified who had 2 or more moderate to severe COPD exacerbations per year. Twenty-nine patients had an underlying antibody deficiency syndrome: common variable immunodeficiency (8), specific antibody deficiency (20), and selective IgA deficiency (1). Twenty-two patients had a follow-up for at least 1 year after treatment of their antibody deficiency, which resulted in a significant reduction of COPD exacerbations, courses of oral corticosteroid use and cumulative annual dose of oral corticosteroid use, rescue antibiotic use, and hospitalizations for COPD exacerbations. This case series identifies antibody deficiency as a potentially treatable risk factor for frequent COPD exacerbations; testing for antibody deficiency should be considered in difficult to manage frequently exacerbating COPD patients. Further prospective studies are warranted to further test this hypothesis.

Limb girdle muscular dystrophy 2I is a slowly progressive muscular dystrophy due to mutations in the Fukutin-related protein ( FKRP) gene. Clinicians are frequently asked if physical activity is harmful for pediatric patients with limb girdle muscular dystrophy 2I. The primary objective of this study was to determine if there is a relationship between self-reported childhood activity level and motor function and respiratory function in older children and adults with limb girdle muscular dystrophy 2I. We compared retrospective self-reported middle school activity level and sport participation with age at onset of weakness, 10-meter walk test, and forced vital capacity later in life in 41 participants with FKRP mutations. We found no relationship between activity level in childhood and disease course later in life, suggesting that self-directed physical activity in children with limb girdle muscular dystrophy 2I does not negatively affect disease progression and outcome.

The objective of this study was to describe the outcomes of patients in the University of Iowa Neuroendocrine Tumor (NET) Database treated with peptide receptor radionuclide therapy (PRRT).One hundred thirty-five patients from the University of Iowa NET Database who received PRRT were analyzed, their characteristics were described, and survival was calculated.The median age at diagnosis was 51 years, and 64% were men. The primary tumor was located in the small bowel (SBNET) in 37.8%, in the pancreas (PNET) in 26.0%, in the lung in 13.3%, in unknown primary in 9.6%, and in other sites in 13.3%. A radiographic response of any magnitude was observed in 65.8%, 11.1% had a mixed response, and 15.4% showed progression. The overall survival (OS) from the first PRRT was 40 months, and the median time to progression was 23.9 months. Higher pretreatment chromogranin A and pancreastatin levels predicted inferior OS.Peptide receptor radionuclide therapy resulted in a relatively long OS and time to progression in heavily pretreated North American patients with advanced NETs. Elevated pretreatment chromogranin A and pancreastatin predicted shorter OS after therapy. Peptide receptor radionuclide therapy is a valuable treatment option in patients with advanced NETs, especially SBNETS.

ImportancePediatric acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) are poorly understood.ObjectiveTo characterize and identify risk factors associated with ARP and CP in childhood.Design, setting, and participantsA multinational cross-sectional study of children with ARP or CP at the time of enrollment to the INSPPIRE (International Study Group of Pediatric Pancreatitis: In Search for a Cure) study at participant institutions of the INSPPIRE Consortium. From August 22, 2012, to February 8, 2015, 155 children with ARP and 146 with CP (aged ≤19 years) were enrolled. Their demographic and clinical information was entered into the REDCap (Research Electronic Data Capture) database at the 15 centers. Differences were analyzed using 2-sample t test or Wilcoxon rank sum test for continuous variables and Pearson χ2 test or Fisher exact test for categorical variables. Disease burden variables (pain variables, hospital/emergency department visits, missed school days) were compared using Wilcoxon rank sum test.Main outcomes and measuresDemographic characteristics, risk factors, abdominal pain, and disease burden.ResultsA total of 301 children were enrolled (mean [SD] age, 11.9 [4.5] years; 172 [57%] female); 155 had ARP and 146 had CP. The majority of children with CP (123 of 146 [84%]) reported prior recurrent episodes of acute pancreatitis. Sex distribution was similar between the groups (57% female in both). Hispanic children were less likely to have CP than ARP (17% vs 28%, respectively; odds ratio [OR] = 0.51; 95% CI, 0.29-0.92; P = .02). At least 1 gene mutation in pancreatitis-related genes was found in 48% of patients with ARP vs 73% of patients with CP (P

Descemet membrane endothelial keratoplasty (DMEK) is an increasingly popular surgical procedure for treating ocular diseases that require a corneal transplant. Previous studies have found that tissue tearing during surgical preparation is more likely elevated in eyes from donors with a history of diabetes mellitus. To quantify these potential differences, we established an experimental technique for quantifying the force required to separate the endothelium-Descemet membrane complex (EDM) from stroma in human donor corneal tissue, and we assessed differences in adhesion strength between diabetic and non-diabetic donor corneas. Transplant suitable corneas were obtained from 23 donors 50–75 years old with an average preservation to assay time of 11.5 days. Corneas were classified from a medical records review as non-diabetic (ND, n = 9), diabetic without evidence of advanced disease (NAD, n = 8), or diabetic with evidence of advanced disease (AD, n = 10). Corneas were sectioned into 3 mm wide strips and the EDM peeled from the stroma. Using the force-extension data obtained from mechanical peel testing, EDM elastic peel tension ( T E ), elastic stiffness ( S E ), average delamination tension ( T D ), and maximum tension ( T MAX ) were calculated. Mean T E , S E , T D , and T MAX values for ND corneas were 0.78 ± 0.07 mN/mm, 0.37 ± 0.05 mN/mm/mm, 0.78 ± 0.08 mN/mm, and 0.94 ± 0.17 mN/mm, respectively. NAD values did not differ significantly. However, AD values for T E (1.01 ± 0.18 mN/mm), T D (1.09 ± 0.21 mN/mm), and T MAX (1.37 ± 0.24 mN/mm) were greater than ND and NAD corneas (P S E did not differ significantly between groups. These findings provide proof of the concept that chronic hyperglycemia from diabetes mellitus results in a phenotypically more adhesive interface between Descemet membrane and the posterior stroma in donor corneal tissue. Results of this study provide a foundation for further investigations into the impact of diabetes on the posterior cornea, eye banking, and keratoplasty.

The current study aimed to examine the relationships between movement and resting pain intensity, pain-related distress, and psychological distress in participants scheduled for total knee arthroplasty (TKA). This study examined the impact of anxiety, depression, and pain catastrophizing on the relationship between pain intensity and pain-related distress. Data analyzed for the current study (N = 346) were collected at baseline as part of a larger Randomized Controlled Trial investigating the efficacy of TENS for TKA (TANK Study). Participants provided demographic information, pain intensity and pain-related distress, and completed validated measures of depression, anxiety, and pain catastrophizing. Only 58% of the sample reported resting pain >0 while 92% of the sample reported movement pain >0. Both movement and resting pain intensity correlated significantly with distress (rs = .86, p

Autism spectrum disorder (ASD) is one phenotypic aspect of many monogenic, hereditary cancer syndromes. Pleiotropic effects of cancer genes on the autism phenotype could lead to repurposing of oncology medications to treat this increasingly prevalent neurodevelopmental condition for which there is currently no treatment. To explore this hypothesis we sought to discover whether autistic patients more often have rare coding, single-nucleotide variants within tumor suppressor and oncogenes and whether autistic patients are more often diagnosed with neoplasms. Exome-sequencing data from the ARRA Autism Sequencing Collaboration was compared to that of a control cohort from the Exome Variant Server database revealing that rare, coding variants within oncogenes were enriched for in the ARRA ASD cohort (p

Background Determining the efficacy of human vaccines that induce antigen-specific protective CD4 T cell responses against pathogens can be particularly challenging to evaluate. Surface expression of CD11a and CD49d has been shown to identify antigen-specific CD4 T cells against viral pathogens in mice. We hypothesized that CD11a and CD49d would also serve as markers of human antigen-specific T cells responding to vaccination. Methods A phase I vaccine trial enabled us to evaluate a novel gating strategy based on surface expression of CD11a and CD49d as a means of detecting antigen-specific, cytokine producing CD4 and CD8 T cells induced after vaccination of naive individuals against leishmaniasis. Three study groups received LEISH-F3 recombinant protein combined with either squalene oil-in-water emulsion (SE) alone, SE with the synthetic TLR-4 ligand glucopyranosyl lipid adjuvant (GLA-SE), or SE with Salmonella minnesota- derived monophosphoryl lipid A (MPL-SE). Individuals were given 3 vaccine doses, on days 0, 28 and 168. Results Starting after the first vaccine dose, the frequency of both CD11a hi CD49d + CD4 and CD11a hi CD49d + CD8 T cells significantly increased over time throughout the 24-week trial. To confirm the role of CD11a hi CD49d + expression in the identification of the antigen-specific T cells, cytokine production was measured following LEISH-F3 stimulation. All of the IFN-γ, TNF-α, and IL-2 producing cells were found within the CD11a hi CD49d + population. Conclusions Our results suggest that the change in the frequency of CD11a hi CD49d + T cells can be used to track antigen-specific CD4 and CD8 T cell responses following T cell-targeted vaccination.

Objective To compare the performance on the American Board of Ophthalmology Written Qualifying Examination (WQE) with the performance on step 1 of the United States Medical Licensing Examination (USMLE) and the Ophthalmic Knowledge Assessment Program (OKAP) examination for residents in multiple residency programs. Design Comparative case series. Participants Fifteen residency programs with 339 total residents participated in this study. The data were extracted from the 5-year American Board of Ophthalmology report to each participating program in 2009 and included residency graduating classes from 2003 through 2007. Residents were included if data were available for the USMLE, OKAP examination in ophthalmology years 1 through 3, and the WQE score. Residents were excluded if one or more of the test scores were not available. Methods Two-sample t tests, logistic regression analysis, and receiver operating characteristic (ROC) curves were used to examine the association of the various tests (USMLE, OKAP examination year 1, OKAP examination year 2, OKAP examination year 3, and maximum OKAP examination score) as a predictor for a passing or failing grade on the WQE. Main Outcome Measures The primary outcome measure of this study was first time pass rate for the WQE. Results Using ROC analysis, the OKAP examination taken at the third year of ophthalmology residency best predicted performance on the WQE. For the OKAP examination taken during the third year of residency, the probability of passing the WQE was at least 80% for a score of 35 or higher and at least 95% for a score of 72 or higher. Conclusions The OKAP examination, especially in the third year of residency, can be useful to residents to predict the likelihood of success on the high-stakes WQE examination. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

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.

The authors examined whether early ultrasound dating (≤20 weeks) of gestational age (GA) in small-for-gestational-age (SGA) fetuses may underestimate gestational duration and therefore the incidence of SGA birth. Within a population-based case-control study (May 2002–June 2005) of Iowa SGA births and preterm deliveries identified from birth records (n = 2,709), the authors illustrate a novel methodological approach with which to assess and correct for systematic underestimation of GA by early ultrasound in women with suspected SGA fetuses. After restricting the analysis to subjects with first-trimester prenatal care, a nonmissing date of the last menstrual period (LMP), and early ultrasound (n = 1,135), SGA subjects’ ultrasound GA was 5.5 days less than their LMP GA, on average. Multivariable linear regression was conducted to determine the extent to which ultrasound GA predicted LMP dating and to correct for systematic misclassification that results after applying standard guidelines to adjudicate differences in these measures. In the unadjusted model, SGA subjects required a correction of +1.5 weeks to the ultrasound estimate. With adjustment for maternal age, smoking, and first-trimester vaginal bleeding, standard guidelines for adjudicating differences in ultrasound and LMP dating underestimated SGA birth by 12.9% and overestimated preterm delivery by 8.7%. This methodological approach can be applied by researchers using different study populations in similar research contexts.

Purpose Previous research has demonstrated relationships of social support with disease-related biomarkers in patients with ovarian cancer. However, the clinical relevance of these findings to patient outcomes has not been established. This prospective study examined how social support relates to long-term survival among consecutive patients with ovarian cancer. We focused on two types of social support: social attachment, a type of emotional social support reflecting connections with others, and instrumental social support reflecting the availability of tangible assistance. Patients and Methods Patients were prospectively recruited during a presurgical clinic visit and completed surveys before surgery. One hundred sixty-eight patients with histologically confirmed epithelial ovarian cancer were observed from the date of surgery until death or December 2010. Clinical information was obtained from medical records. Results In a Cox regression model, adjusting for disease stage, grade, histology, residual disease, and age, greater social attachment was associated with a lower likelihood of death (hazard ratio [HR], 0.87; 95% CI, 0.77 to 0.98; P = .018). The median survival time for patients with low social attachment categorized on a median split of 15 was 3.35 years (95% CI, 2.56 to 4.15 years). In contrast, by study completion, 59% of patients with high social attachment were still alive after 4.70 years. No significant association was found between instrumental social support and survival, even after adjustment for covariates. Conclusion Social attachment is associated with a survival advantage for patients with ovarian cancer. Clinical implications include the importance of screening for deficits in the social environment and consideration of support activities during adjuvant treatment.

Background Chemokines and cytokines may occur in dentinal fluids in response to local infection and inflammation. To test this hypothesis, we assessed the presence and concentration of inflammatory mediators in fluid extracted from the coronal occlusal dentine of trimmed teeth. Design Freshly extracted sound, carious, and restored molars were trimmed through the enamel to expose the underlying dentine, etched with 35% phosphoric acid, and rinsed. Fluid was extracted from the coronal occlusal dentine of these trimmed teeth by centrifugation at 2750 × g for 30 min. Results When assessed by MALDI-TOF, fluid extracted from the coronal occlusal dentine from 16 molars contained at least 117 peaks with different masses suggesting that this fluid was rich with molecules within the appropriate mass range of potential mediators. Indeed, when assessed for chemokines and cytokines, fluid extracted from the coronal occlusal dentine from 25 extracted molars with caries lesions, 10 extracted restored molars with occlusal amalgam, and 77 extracted sound molars contained IL-1β, TNF-α, IL-6, IL-8, IL-12(p70), and IL-10. A significant elevation was found for TNF-α ( p = 0.041) in extracted fluid from teeth restored with amalgam fillings. Conclusions Overall, fluid extracted from the coronal occlusal dentine of trimmed teeth may be useful in identifying proteins and other molecules in dentine and pulpal fluids and determining their role as mediators in the pathogenesis of oral infection and inflammation.

To evaluate the prevalence of musculoskeletal disorders among eye care physicians compared with family medicine physicians.Case control study.Ophthalmologists and optometrists at the University of Iowa and Mayo Clinic (participants) and family medicine physicians at the University of Iowa and Mayo Clinic (controls).An electronic survey was e-mailed to all subjects.The prevalence of musculoskeletal symptoms between eye care providers and family medicine physicians (control group).One hundred eight-six surveys were completed by 94 eye care physicians and 92 family medicine physicians with a response rate of 99% and 80%, respectively. There were no significant differences between the 2 groups with regard to mean age, gender, body mass index, years with current employer, or years in practice. Eye care providers, compared with their family medicine colleagues, reported a higher prevalence of neck (46% vs 21%; P0.01), hand/wrist pain (17% vs 7%; P = 0.03), and lower back pain (26% vs 9%; P0.01). A greater proportion of eye care physicians classified their job as a high-strain job (high demand, low control; 31% vs 20%) and a lower proportion classified their job as an active job (high demand, high control; 24% vs 47%; p = 0.01). Several job factors reported by eye care providers to contribute to musculoskeletal symptoms included performing the same task repeatedly, working in awkward/cramped positions, working in the same position for long periods, and bending/twisting the back (all P0.01).In this survey, the study group, composed of ophthalmologists and optometrists, had a higher prevalence of neck, hand/wrist, and lower back pain compared with family medicine physicians; repetitive tasks, prolonged or awkward/cramped positions, and bending/twisting were contributory factors. Given the ramifications of these findings, future efforts should concentrate on modifications to the eye care providers' work environment to prevent or alleviate musculoskeletal disorders and their personal and socioeconomic burden.

Characterization of the behavior of red blood cells (RBCs) in the bloodstream after transfusion (i.e., posttransfusion RBC kinetics) generally consists of measurement of RBC volume (RCV) and RBC survival (RCS) assessed by posttransfusion recovery at 24 hours (PTR24) and at later times, that is, to 50% survival (T50) and to the mean potential life span (MPL). Posttransfusion RBC kinetic studies provide information valuable in establishing the diagnosis and defining the pathogenesis of hematologic conditions and in determining optimal RBC transfusion and blood banking practices.1 Ideally, techniques for measuring posttransfusion RBC kinetics should be precise, safe, and easily applied. They should also be broadly applicable to diverse study populations and require minimal blood volumes for sampling, labeling, and analysis—particularly for infants. Methods utilizing chromium-51 (51Cr) radionuclide RBC labeling have been adopted by the International Committee for Standardization in Hematology as the reference method for determining posttransfusion RCS in humans.2 Unfortunately, because some species experience excessive rates of loss of 51Cr from RBCs (3%–4% per day in sheep, horses, cattle, goats, cats, and rats, compared to approx. 1% in humans),3 the 51Cr labeling method is not reliable for all mammalian species. Moreover, the costs for radiation containment and disposal are substantial and increasing. Recently, a method based on biotin-labeled RBCs (BioRBC) that does not require radiation exposure has been developed and validated for use in posttransfusion kinetic studies in a broad spectrum of mammalian species. In addition to overcoming the aforementioned limitations of the 51Cr method, the BioRBC method achieves similar sensitivity while requiring analytic blood volumes as small as 3 μL4,5 compared to the 1 to 2 mL recommended for the 51Cr method.3 The focus of this study was on validating the BioRBC labeling method in sheep. This is important because ovine fetal and newborn cardiovascular, pulmonary, and of relevance for this report, hematologic development and physiology resemble those of humans.6 In particular, ovine erythropoiesis in the fetus, neonate, and adult is similar to the human, and regulation of erythropoiesis and RBC kinetics in the ovine model are currently active areas of study.7–10 Accordingly, lambs and sheep are logical animal models for preclinical testing of this method for measuring RCV and RCS. We recently demonstrated that autologous sheep RBCs labeled at four discrete, low biotin densities yielded RCV results that are equivalent to one another and are within 10% of values determined simultaneously using [14C]cyanate-labeled RBCs.11 Further, we have applied the multidensity method to measurement of RCV in human adults with similar success. We were able to extend these human studies to survival of the BioRBCs and determine short-term and long-term RCS in eight participants. However, use of a radioactive-labeled marker such as 51Cr was not included because of the technical and financial demands. In this study, we extend these preclinical animal studies to assess the validity of RCS determined in the same animals using RBCs labeled with the same four biotin densities and with [14C]cyanate. Because of the additional complexities of dealing with an animal with a large spleen that sequesters up to 30% of RBCs, of the difficulties of measuring radiolabeled RBCs, and the need to fit a mathematical curve to accurately determine the proportion of each of the BioRBC peaks, we have only recently completed this analysis for the current report. To do so, we assessed short-term RCS by PTR24 and long-term RCS by T50 and by MPL. For long-term RCS, we hypothesized that these two variables would agree closely when determined using RBCs labeled with the lower BioRBC densities and that they would agree with RCS determined using [14C]cyanate.12

Objective To investigate systematically the role of anti–platelet-aggregating drugs or anticoagulants in central retinal vein occlusion (CRVO) and hemi-CRVO. Design Cohort study. Participants Six hundred eighty-six consecutive patients with CRVO (567 patients, 585 eyes) and nonischemic hemi-CRVO (119 patients, 122 eyes). Methods At first visit, all patients had a detailed ophthalmic and medical history (including the use of anti–platelet aggregating drugs or anticoagulants), and comprehensive ophthalmic and retinal evaluation. Visual evaluation was carried out by recording visual acuity, using the Snellen visual acuity chart, and visual fields with a Goldmann perimeter. The same ophthalmic evaluation was performed at each follow-up visit. At the initial visit, CRVO and hemi-CRVO were classified as nonischemic and ischemic. Main Outcome Measures Visual acuity, visual fields, and severity of retinal hemorrhages. Results All 3 types of CRVO, showed a significantly greater severity of retinal hemorrhages among aspirin users than nonusers ( P P = 0.020). Of those whose macular edema resolved, overall cumulative visual acuity outcome also suggested a higher percentage with deterioration among aspirin users, odds ratio for deterioration of 3.62 (95% CI, 0.97–13.54; P = 0.05) for aspirin users relative to nonusers. For the nonischemic CRVO patients with 20/70 or worse visual acuity at the initial visit, after resolution of macular edema, improvement in visual acuity was less likely in the aspirin users than in nonusers (odds ratio, 0.18; 95% CI, 0.04–0.72; P = 0.016). Conclusions Findings of this study indicate that, for patients with CRVO and hemi-CRVO, the use of aspirin, other anti–platelet aggregating agents, or anticoagulants was associated with a worse visual outcome and no apparent benefit. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

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.