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Background: The majority of youth with type 1 diabetes (T1D) fail to meet glycemic targets despite increasing continuous glucose monitoring (CGM) use. We therefore aimed to determine the proportion of caregivers who review recent glycemic trends (“retrospective review”) and make ensuant insulin adjustments based on this data (“retroactive insulin adjustments”). We additionally considered that fear of hypoglycemia and frequency of severe hypoglycemia would be associated with performing retrospective review. Methods: We conducted a cross-sectional survey of caregivers of youth with T1D, collecting demographics, diabetes technology usage, patterns of glucose data review/insulin dose self-adjustment, and Hypoglycemia Fear Survey (HFS). Results: Nineteen percent of eligible caregivers (191/1003) responded. Performing retrospective review was associated with younger child age (12.2 versus 15.4, P = .0001) and CGM use (92% versus 73%, P = .004), but was not associated with a significant improvement in child’s HbA1c (7.89 versus 8.04, P = .65). Retrospective reviewers had significantly higher HFS-behavior scores (31.9 versus 27.7, P = .0002), which remained significantly higher when adjusted for child’s age and CGM use ( P = .005). Linear regression identified a significant negative association between HbA1c (%) and number of retroactive insulin adjustments (0.24 percent lower mean HbA1c per additional adjustment made, P = .02). Conclusions: Retrospective glucose data review is associated with improved HbA1c when coupled with data-driven retroactive insulin adjustments. Barriers to data downloading existed even in this cohort of predominantly CGM-using T1D families.

BACKGROUND: Among adults with in-hospital cardiac arrest (IHCA), overall survival is lower in black patients compared to white patients. Data regarding racial differences in survival for pediatric IHCA are unknown. METHODS: Using 2000–2017 data from the American Heart Association Get With the Guidelines-Resuscitation® registry, we identified children >24 hours and < 18 years of age with IHCA due to an initial pulseless rhythm. We used generalized estimation equation to examine the association of black race with survival to hospital discharge, return of spontaneous circulation (ROSC), and favorable neurologic outcome at discharge. RESULTS: Overall, 2940 pediatric patients (898 black, 2042 white) at 224 hospitals with IHCA were included. The mean age was 3.0 years, 57% were male and 16% had an initial shockable rhythm. Age, sex, interventions in place at the time of arrest and cardiac arrest characteristics did not differ significantly by race. The overall survival to discharge was 36.9%, return of spontaneous circulation (ROSC) was 73%, and favorable neurologic survival was 20.8%. Although black race was associated with lower rates of ROSC compared to white patients (69.5% in blacks vs. 74.6% in whites; risk-adjusted OR 0.79, 95% CI 0.67 – 0.94, P= 0.016), black race was not associated with survival to discharge (34.7% in blacks vs. 37.8% in whites; risk-adjusted OR 0.96, 95% CI 0.80 – 1.15, P=0.68) or favorable neurologic outcome (18.7% in blacks vs. 21.8% in whites, risk-adjusted OR 0.98, 95% CI 0.80–1.20, p=0.85). CONCLUSIONS: In contrast to adults, we did not find evidence for racial differences in survival outcomes following IHCA among children.

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).

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.

IMPORTANCE: Intimate partner violence (IPV) is a substantial cause of morbidity and mortality in the US. Previous studies indicate gaps in identifying and referring female patients with IPV-associated orbital and ocular injuries to ancillary services. OBJECTIVE: To determine the number of IPV-associated orbital floor fractures, zygomaticomaxillary complex (ZMC) fractures, and ruptured globes referred to ancillary services in adult female patients following an educational and screening intervention to health care professionals. DESIGN, SETTING, AND PARTICIPANTS: This single-center retrospective quality improvement analysis examined electronic medical records of adult female patients seen in a single level 1 trauma center emergency department and ophthalmology clinic between January 2015 and February 2019, after the initiative began. Female adults who sustained orbital floor fractures, ZMC fractures, or ruptured globes were included. Preinitiative data were previously collected between January 1995 and January 2015 on adult female patients and published. Data analysis for this study occurred from May 2020 to September 2020. INTERVENTIONS: A 2-part, ongoing initiative began January 2015. First, enhancement of IPV screening protocols in the emergency department was conducted. Second, an educational campaign on IPV injury patterns was presented to residents and faculty in ophthalmology, emergency, otolaryngology, and trauma departments. MAIN OUTCOMES AND MEASURES: Comparison of ancillary service involvement preinitiative (January 1995 to January 2015) and postinitiative (January 2015 to February 2019). RESULTS: A total of 216 adult female patients (mean [SD] age, 55.0 [22.7] years; age range, 18-99 years) sustained orbital floor or ZMC fractures postinitiative. A total of 22 of 216 (10.2%) sustained fractures from IPV compared with 31 of 405 (7.6%) preinitiative (95% CI, −2.2% to 7.3%; P = .28). Documented social work referrals (11 of 31 preinitiative vs 20 of 22 postinitiative; difference, 55% [95% CI, 35%-76%]; P

No studies exist to determine the optimal timing to counsel women regarding postpartum contraception which means opportunities for immediate postpartum contraception are often missed. Women between...

Background: Office-based biofeedback therapy is effective for constipation with dyssynergic defecation, but must be performed by skilled staff, is only available in selected centres, and requires multiple visits. The efficacy of home-based biofeedback therapy is unknown. We compared clinical and subjective outcomes with home-based and office-based approaches. Methods: In this randomised controlled trial, eligible patients were adult outpatients (age 18–80 years) who met the Rome III criteria for functional constipation and who had been referred to a tertiary-care centre after non-response to routine management, and who had dyssynergic defecation. Patients were randomly assigned according to a schedule generated in advance by the study biostatistician, in permuted blocks of four, to receive office-based or home-based biofeedback therapy. Office-based biofeedback comprised therapist-guided pelvic floor training for six sessions over 3 months (visits every 2 weeks). Home-based biofeedback comprised 20 min self-training sessions twice per day, in which a self-inserted probe was used to provide visual feedback via a handheld monitoring device of anal sphincter pressure and push effort. Patients recorded in diaries the time of each defecation attempt, stool consistency, straining effort, feeling of incomplete evacuation, need for digital assistance with stooling, and satisfaction with bowel function, from 1 week before enrolment to the end of follow-up. Treatment responders were defined post hoc as those with normalisation of dyssynergic defecation and an increase in the number of complete spontaneous bowel movements per week by 3 months. Cost outcomes calculated from health-care costs and loss of salary were assessed from hospital billing and medical records and questionnaires. Primary outcome measures were the presence of a dyssynergic pattern during attempted defecation, balloon expulsion time, the number of complete spontaneous bowel movements per week, and satisfaction with bowel function, assessed by intention to treat (non-inferiority) and per protocol. This trial is registered with ClinicalTrials.gov, number NCT03202771. Findings: Of 300 patients screened we enrolled 100, from Jan 7, 2005, to Jan 31, 2010. 83 patients completed training (38 [76%] of 50 in the home-based biofeedback group and 45 [90%] of 50 in the office-based biofeedback group). 34 (68%) patients in the home-based group and 35 (70%) in the office-based group were classified as responders. All primary outcomes improved significantly from baseline in the two treatment groups (all p

BACKGROUND Children, caregivers, and clinicians often prefer midstream clean catch technique to urethral catheterization for obtaining urine cultures. However, contamination is common, potentially resulting in unnecessary medical intervention and cost. With this resident-led initiative, we aimed to reduce pediatric midstream clean catch urine culture contamination over 6 months. METHODS A bundled intervention was implemented in the emergency department, inpatient units, and outpatient clinics at our institution. Baseline contamination rates were collected April 2016 to September 2017; the intervention was introduced October 2017 to March 2018 and evaluated April 2018 to September 2018. Sustainability was measured October 2018 to September 2020. Balancing measures included rates of repeat urine cultures, positive cultures, and contaminated cultures by urethral catheterization. RESULTS Rates of midstream clean catch urine culture contamination were 45.3% preintervention and 30.9% postintervention, a 14.7% (95% confidence interval: 8.0% to 21.5%) absolute decrease. Before and after intervention, girls and patients 16 to 17 years old had the highest rates of midstream clean catch contamination. Six months postintervention, the rate of repeat urine culture decreased from 4.9% to 0.9% with no change in positive culture results or contaminated cultures by urethral catheterization. Over the subsequent 2 years, the impact of the intervention decreased (rate of contamination over 30 months postintervention: 38.4%, a 7.3% [95% confidence interval: 2.9% to 11.6%] absolute decrease; rate of repeat urine culture: 3.2%). CONCLUSIONS An intervention to improve midstream clean catch urine culture collection was associated with a clinically meaningful decrease in contamination. Impact of the resident-led intervention decreased over time.

Transcutaneous Electrical Nerve Stimulation (TENS) is a safe, economical non-pharmacological adjunctive intervention. Using data from the Fibromyalgia Activity Study with TENS (FAST) we performed a responder analysis to identify predictors of reduced pain and fatigue after 1-month of daily TENS use in women with FM. Women with FM were randomly assigned to active-TENS (2-125Hz; highest-tolerable intensity), placebo-TENS, or no-TENS for 1-month. After the randomized phase, placebo-TENS and no-TENS groups received active-TENS for 1-month. Responders to TENS were defined as those achieving a 30% reduction in movement-evoked pain and/or 20% reduction in movement-evoked fatigue., The predictor model was developed using data from the randomized phase of the active-TENS group (n=103) and validated using data from the placebo-TENS and no-TENS groups after active-TENS for 1 month (n=155). Participant characteristics, and changes in pain, fatigue, and function were assessed as potential predictors using a logistic regression model. Number needed to treat (NNT), and number needed to harm (NNH) calculations were made comparing the active-TENS group to the placebo-TENS and no-TENS groups using an intention-to-treat analysis. Predictors of clinical improvement in pain at 1-month follow-up were initial decrease in pain during the first TENS use and widespread pain index (AUC=0.80; 95%CI: 0.73,0.87). Predictors of clinical improvement in fatigue at 1-month follow-up were marital status, sleep impairment and initial decrease in fatigue during the first TENS use (AUC=0.67; 95%CI: 0.58,0.75). NNT for pain and fatigue ranged between 3.3-5.3. NNH ranged from 20-100 for minor TENS-related adverse events. The current study shows that 1 in 3 women with FM will experience a clinically significant reduction in pain, while 1 in 5 will experience a clinically significant reduction in fatigue with minimal harms. How a person responds to the first TENS treatment predicts response to daily use over of a 1-month period. Trial Number: NCT01888640, Funded by NIH UM1 AR06338, NIH UM1 AR063381-S1, T32 NS045549-12, and K99AR071517.

Most patients needing diabetic tractional retinal detachment (TRD) surgery are working-age adults that drive and participate in other vision-dependent activities of daily living. We sought to determine the proportion of patients that achieve functional visual acuity (VA) based on the World Health Organization (WHO) definition of ‘low vision’ (≤ 20/80) and US driving standards (≥ 20/40) after vitrectomy for diabetic TRD. In this 10-year retrospective review, consecutive patients who underwent primary vitrectomy for TRD from proliferative diabetic retinopathy were studied. 240 eyes in 203 patients met criteria for analysis (38 eyes were lost to follow up at 3 months; 68 at 12 months; 146 at 60 months). While most patients (nearly 80%) having TRD surgery had low vision pre-op, almost half attained VA that was > 20/80 five years post-op. Those most likely to achieve significant visual improvement (p

Purpose To assess how trypan blue staining affects Descemet membrane endothelial keratoplasty (DMEK) graft visibility and corneal endothelial cell (CEC) mitochondrial respiration. Methods DMEK grafts (n = 20) were stained with trypan blue 0.06% for 1, 3, 5, or 10 minutes. Each graft was injected into an artificial anterior chamber. Surgery was simulated with tapping and sweeping motions on the corneal surface and injections of balanced salt solution (BSS). Graft visibility was assessed at 5, 10, 20, and 30 minutes. Effects of trypan blue on mitochondrial respiration were assessed using primary CECs cultured from donor corneas (n = 43). Treatment wells exposed to trypan blue 0.06% (1, 5, or 30 minutes) and donor-matched control wells to methylene blue 1% (1 minute) or BSS (1, 5, or 30 minutes) were assayed for key respiration parameters. Results After 5 minutes of surgical manipulation, grafts stained for 5 minutes were significantly more visible than grafts stained for 1 or 3 minutes; there was no added benefit of staining for 10 minutes. After 10 minutes of surgical manipulation, grafts stained for 3 minutes were more visible than grafts stained for 1 minute, without additional benefits of staining ≥5 minutes. No visibility differences were observed after ≥20 minutes of surgical manipulation. CEC mitochondrial respiration did not change significantly following trypan blue exposure for all intervals tested compared to BSS. Conclusions Staining DMEK grafts with trypan blue for 3 to 5 minutes optimizes visibility during surgical manipulation without mitochondrial impairment. Corneal surgeons learning DMEK will benefit from optimizing this critical step.

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.

Background Mild traumatic brain injury (mTBI) is a signature wound of Veterans of operations in Iraq and Afghanistan (i.e., OIF/OEF/OND). Most Veterans with mTBI also experience stress-based psychopathology (e.g., depression, posttraumatic stress disorder) and chronic pain. This combination – referred to as polytrauma - results in detrimental long-term effects on social, occupational, and community reintegration. This study will compare the efficacy of a one-day Acceptance and Commitment Training plus Education, Resources, and Support (ACT+ERS) workshop to a one-day active control group (ERS) on symptoms of distress and social, occupational, and community reintegration. We will also examine mediators and moderators of treatment response. Methods This is an ongoing randomized clinical trial. 212 OIF/OEF/OND Veterans with polytrauma are being recruited. Veterans are randomly assigned to a one-day ACT+ERS or a one-day ERS workshop with two individualized booster sessions approximately two- and four-weeks post-workshop. Veterans complete assessments prior to the workshop and again at six weeks, three months, and six months post-workshop. Of note, workshops were converted to a virtual format due to the COVID-19 pandemic. Results The primary outcomes are symptoms of distress and reintegration; secondary outcomes are post-traumatic stress disorder symptoms and pain interference. Secondary analyses will assess whether changes in avoidance at three months mediate changes in distress and reintegration at six months. Conclusion Facilitating the psychological adjustment and reintegration of Veterans with polytrauma is critical. The results of this study will provide important information about the impact of a brief intervention for Veterans with these concerns.

This study examined whether depression and anxiety differentially relate to fatigue, sleep disturbance, pain catastrophizing, fear of movement, and pain severity in women with fibromyalgia. Baseline data from the Fibromyalgia Activity Study with Transcutaneous Electrical Nerve Stimulation were analyzed. Of 191 participants, 50 percent reported high anxiety and/or depression (17% high anxiety, 9% high depression, and 24% both). Fatigue and sleep impairment were associated with high depression ( p

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 determine the incidence of positive corneoscleral donor rim fungal cultures after keratoplasty and to report clinical outcomes of grafts with culture-positive donor rims. Design Retrospective cohort study. Participants Consecutive donor corneas and keratoplasty recipients at a single tertiary referral center over 20 years. Methods Patient charts were reviewed to determine the incidence of positive donor rim fungal cultures and clinical outcomes of all grafts using contaminated tissue. Main Outcome Measures The primary outcome measures were positive donor rim fungal culture results and the development of postkeratoplasty fungal infection using corresponding corneal tissue. The secondary outcome measure was the impact of postoperative prophylaxis on donor tissue-associated infections. Results A total of 3414 keratoplasty cases were included in the statistical analysis. Seventy-one cases (2.1%) were associated with a fungal culture-positive donor rim. Candida species were cultured in 40 cases (56.3%). There was a higher incidence of positive rim cultures over the last 5 years of the analytic period compared with the first 15 years ( P = 0.018). Fungal keratitis developed in 4 cases (5.6%), and all patients required further surgical intervention to achieve cure. There were no cases of fungal endophthalmitis. Empiric antimycotic prophylaxis initiated at the time of positive culture result reduced the incidence of keratitis from 15.8% in untreated cases to 1.9% in treated cases ( P = 0.056). Conclusions Positive donor rim fungal cultures are uncommon, but carry an unacceptably high risk of postoperative fungal infection. This risk may be reduced with prophylactic antimycotic therapy when culture-positive donor rims are identified.

BACKGROUND: There are limited data on outcomes of extracranial-intracranial (EC-IC) bypass in patients with recurrent hemispheric syndromes due to atherosclerotic internal carotid artery occlusion (AICAO). OBJECTIVE: To compare clinical outcomes and efficacy of EC-IC bypass surgery in patients with and without recurrent hemispheric syndromes associated with AICAO in the Carotid Occlusion Surgery Study (COSS). METHODS: In patients enrolled in the COSS trial, we compared baseline characteristics and clinical outcomes for participants with (rHEMI+) and without recurrent hemispheric ischemia (rHEMI−) prior to randomization into surgical vs medical groups. The primary outcome was all stroke and death from randomization through 30 d and ipsilateral ischemic stroke within 2 yr. RESULTS: Of 195 randomized participants, 100 were rHEMI+ (50 in each group). Baseline characteristics between rHEMI+ and rHEMI− participants were similar except rHEMI+ were more likely to have had previous stroke prior to randomization (61% vs 20%, P

Purpose: To compare Descemet membrane endothelial keratoplasty (DMEK) outcomes using nondiabetic grafts in diabetic and nondiabetic recipients. Methods: All eyes that underwent DMEK between February 2013 and October 2016 (follow-up ≥3 months, without prior keratoplasty) were included. Recipients were divided into diabetic (insulin dependent [IDDM] or noninsulin dependent [NIDDM]) and nondiabetic groups. Main outcome measures included postoperative visual acuity, rebubble procedure rates, and graft failure rates. Results: Of 334 eyes (243 subjects) included for analysis, 63 eyes (18.8%) were from diabetic recipients. At each timepoint, best-corrected visual acuity trended lower for IDDM recipients compared to NIDDM and nondiabetic recipients. There were no statistically significant differences in rebubble rates of diabetic compared to nondiabetic recipients (20.6% vs. 12.9%, p = 0.17), or IDDM compared to nondiabetic recipients (27.3% vs. 12.9%, p = 0.08; hazard ratio 2.26). Overall, 13 grafts (3.9%) failed (mean follow-up, 565 days; range, 90–1293 days). Graft failures did not differ between diabetic and nondiabetic recipients (4.0% vs. 4.9%, p = 0.15) regardless of subgroup (p = 0.36). Conclusions: DMEK provides excellent outcomes for patients with and without diabetes. DMEK outcomes were excellent with improvements in visual acuity and low rates of graft failure. Our findings were unable to determine differences between rebubble procedure rates but do emphasize the need for further research using stratified groups based on diabetes severity. Keywords: Corneal endothelium, DMEK, Diabetes mellitus, Descemet membrane, Endothelial keratoplasty, Corneal transplantation

The Patient Reported Outcomes Measurement System (PROMIS) offers standardized assessment measures of clinically relevant patient reported outcomes. This study evaluated the reliability and validity of select PROMIS measures with United States Military Veterans following orthopedic surgery. Data for the current study were collected as part of a pilot randomized control trial assessing the efficacy of a one day Acceptance and Commitment Therapy workshop on persistent post-surgical pain in at-risk Veterans undergoing orthopedic surgery. Sixty-seven participants completed surveys three months after surgery. Participants completed the following PROMIS instruments: PROMIS Anxiety Short Form 8a, PROMIS Depression Short Form 8b, and PROMIS pain interference short form 8a. PROMIS measures were compared to the Generalized Anxiety Disorder 7-item scale (GAD-7), the Patient Health Questionnaire 9-item scale (PHQ-9), and the Brief Pain Inventory (BPI) pain interference subscale (respectively). All three PROMIS measures demonstrated excellent internal consistency (Cronbach’s alphas ranged from .93 - .96) and each loaded onto a single factor. The PROMIS measures were moderately correlated with their respective comparison measures (r = .69 - .76). The PROMIS anxiety and PROMIS depression measures were highly correlated to one another (r = .91). Findings highlight the potential utility of these PROMIS measures in Veterans following orthopedic surgery and the overlap between the PROMIS depression and anxiety measures in this sample.

ObjectiveThe aim of the study was to determine the rate of progression from acute recurrent pancreatitis (ARP) to chronic pancreatitis (CP) in children and assess risk factors.Study designData were collected from the INternational Study group of Pediatric Pancreatitis: In search for a cuRE (INSPPIRE) cohort. Kaplan-Meier curves were constructed to calculate duration of progression from initial attack of acute pancreatitis (AP) to CP. Log-rank test was used to compare survival (nonprogression) probability distribution between groups. Cox proportional hazard regression models were fitted to obtain hazard ratio (with 95% confidence interval [CI]) of progression for each risk variable.ResultsOf 442 children, 251 had ARP and 191 had CP. The median time of progression from initial attack of AP to CP was 3.79 years. The progression was faster in those ages 6 years or older at the first episode of AP compared to those younger than 6 years (median time to CP: 2.91 vs 4.92 years; P = 0.01). Children with pathogenic PRSS1 variants progressed more rapidly to CP compared to children without PRSS1 variants (median time to CP: 2.52 vs 4.48 years; P = 0.003). Within 6 years after the initial AP attack, cumulative proportion with exocrine pancreatic insufficiency was 18.0% (95% CI: 12.4%, 25.6%); diabetes mellitus was 7.7% (95% CI: 4.2%, 14.1%).ConclusionsChildren with ARP rapidly progress to CP, exocrine pancreatic insufficiency, and diabetes. The progression to CP is faster in children who were 6 years or older at the first episode of AP or with pathogenic PRSS1 variants. The factors that affect the aggressive disease course in childhood warrant further investigation.

OBJECTIVE. Oncologic breast surgeries carry a risk for persistent postsurgical pain. This study was a randomized pilot and feasibility study of a single-session Acceptance and Commitment Therapy (ACT) intervention compared to treatment as usual among women undergoing surgery for breast cancer or ductal carcinoma in situ (DCIS). METHODS. Participants were recruited via letter of invitation and follow-up phone call from a single site in the United States from 2015–2017. Participants were at risk for persistent post-surgical pain, based on: young age (3 on a 0–10 numeric rating scale) in the operative breast or with arm movement. Written qualitative responses indicated that the majority of participants who received the intervention understood the concepts presented and reported continued practice of exercises learned in the session. The between group effect sizes for moderate-severe pain and elevated anxiety at 3-months post-surgery were small (Phi=0.08 and 0.16, respectively). The between group effect sizes for depression, pain acceptance, and pain catastrophizing at 3-months post-surgery were minimal. CONCLUSIONS. This study found small positive effects on post-surgical pain and anxiety for a single-session ACT intervention among women with breast cancer. This study supports the use of ACT with this population.

Objective Data on the practice of self-managed medication abortion are limited, in part because this practice takes place purposefully outside of established healthcare systems. Given this, we aimed to ascertain abortion providers' familiarity with self-managed medication abortion and associated complications, compare regional differences and evaluate provider attitudes. Study design We distributed an online survey to members of Society for Family Planning, Association of Reproductive Health Providers and the Abortion Care Network between July and September 2017 querying experiences with and opinions about self-managed abortion. Results Of 650 respondents, 359 (55.1%) were direct abortion providers. Two hundred and thirty of 335 providers (68.6%) had experience with women trying to interrupt pregnancies on their own, and of those, 153 (76.1%) had seen use of misoprostol and/or mifepristone, and 204 of 342 (59.6%) thought this practice increased in the past 5 years. One hundred and seventeen of 335 (34.9%), witnessed complications from self-managed abortion with misoprostol/mifepristone, most commonly incomplete abortion and less often hemorrhage, sepsis and uterine rupture. Half of providers, 171 of 321 (53.3%), think that the use of misoprostol/mifepristone for the self-management of abortion is safe. Conclusion Two thirds of respondents had experiences with women attempting to self-manage abortion, and about a third witnessed complications related to self-managed medication abortion. About half of respondents agreed that self-managed abortion is safe. Implications This study establishes that self-managed abortion is a practice which a majority of respondents have seen among their patients and, because of its prevalence, an area that warrants further research.

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

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.

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.

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).

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.

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.

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.

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.

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.