USA Objective Research Articles

Cost of opioid medication abuse with and without tampering in the USA.

ObjectiveTo provide per-patient estimates of the economic burden for opioid medication abuse with and without tampering.Patients and methodsAdults in the US who participated in the 2010 and/or 2011 National Health and Wellness Survey were resurveyed to provide information on use and abuse of prescription opioids in the previous 3 months. Participants (N=20,885) were categorized as those who abused and tampered (n=107), abused without tampering (n=118), those who reported using of opioids as prescribed (n=981), and non-opioid controls (n=19,679). Average wages from the Bureau of Labor Statistics and health care unit costs from the Truven MarketScan database were applied to self-reported work impairment (absenteeism, presenteeism, and overall work impairment) and health care resource utilization (health care provider visits, emergency room visits, hospitalizations, and drug rehabilitation) to estimate indirect and direct medical costs, respectively. Estimated mean costs for these groups were compared using analysis of variance, and generalized linear models were used to compare costs adjusted for confounders.ResultsThose who abused and tampered had significantly higher mean indirect (work impairment: $3,614 vs $2,938, p<0.05) and direct (health care use: $23,328 vs $4,514, p<0.001) costs over 3 months than those who abused without tampering. This included higher mean incremental costs for non-opioid-related medical visits ($14,180 vs $2,236, p<0.001), opioid-related medical visits ($8,790 vs $2,223, p<0.001), and drug rehabilitation ($358 vs $55, p<0.001). Increased total direct costs were associated with tampering after adjusting for confounders (p<0.001). Median incremental costs were also higher among those who tampered.ConclusionTampering with prescription opioid medications is associated with significantly increased medical costs compared to abuse without tampering. Reducing tampering may provide net health care savings.

Cost-effectiveness analysis of intravenous ferumoxytol for the treatment of iron deficiency anemia in adult patients with non-dialysis-dependent chronic kidney disease in the USA.

ObjectiveFerumoxytol has demonstrated superior efficacy compared with oral iron in treating iron deficiency anemia in chronic kidney disease (CKD) patients. However, an economic evaluation of ferumoxytol has not been conducted. The aim of this study was to analyze the cost-effectiveness of treating iron deficiency anemia in adult non-dialysis-dependent CKD patients with ferumoxytol as compared with oral iron, alone or in combination with erythropoietin-stimulating agents (ESAs).MethodsA decision analytic model compared health outcomes and costs associated with 5-week outpatient treatment of adult non-dialysis-dependent CKD patients with ferumoxytol or oral iron, each as monotherapy or in combination with ESAs in the USA. Direct costs include the following: drug acquisition and administration, adverse events, and medical management. Efficacy was determined as mean increase in hemoglobin (g/dL) from baseline over the 5-week period. Clinical inputs were derived from patient-level data from two Phase III randomized controlled trials of ferumoxytol vs. oral iron in non-dialysis-dependent CKD patients, and cost inputs from RED BOOK™ and Centers for Medicare and Medicaid Services data. Sensitivity analyses were performed to identify cost drivers and assess the stability of results.ResultsThe 5-week treatment cost was $2,489, $5,216, $1,298, and $4,263 per patient for ferumoxytol, ferumoxytol with ESAs, oral iron, and oral iron with ESAs, respectively. The corresponding incremental costs per g/dL increase in hemoglobin, relative to ferumoxytol alone, were $398, $3,558, and $4,768 per patient. Efficacy was the main driver of cost-effectiveness for all treatments. Adverse event and medical management costs were the principal drivers of oral iron monotherapy costs, while drug acquisition substantially contributed to the overall cost for the remaining treatments.ConclusionThese results suggest that ferumoxytol is a cost-effective treatment for iron deficiency anemia in non-dialysis-dependent CKD patients over a 5-week period compared with oral iron with or without ESAs. Ferumoxytol is more cost-effective as monotherapy.

First trimester infection with Listeria monocytogenes is characterized by decidual and placental inflammation in pregnant cynomolgus macaques

First trimester infection with Listeria monocytogenes is characterized by decidual and placental inflammation in pregnant cynomolgus macaques

In vivo localisation and vascular effects of nano-vesicles derived from normal first trimester human placentae

In vivo localisation and vascular effects of nano-vesicles derived from normal first trimester human placentae

The human placenta: Function and morphological assessments using ultrasound and magnetic resonance elastography

s / Placenta 45 (2016) 63e133 74 P1.6 THE HUMAN PLACENTA: FUNCTION AND MORPHOLOGICAL ASSESSMENTS USING ULTRASOUND AND MAGNETIC RESONANCE ELASTOGRAPHY Richard K. Miller , Stephan McAleavey , Juvenal Ormachea , Eva Pressman, Loralei Thornburg , David Dombroski , Jianhui Zhong, Marvin Doyley , Ronald W. Wood, Jonathan Carrol-Nellenback , Ollivier Hyrien , Philip Katzman , Christopher Stodgell , Kam Szlachetka, Henry Wang, Kevin Parker . University of Rochester School of Medicine and Dentistry, Rochester, New York, USA; University of Rochester Haijm School of Engineering, Rochester, New York, USA Objective: In utero evaluations of placental anatomy and function offer the promise of associating placental pathophysiology with neonatal outcomes, and thus potential for enhanced management of perinatal complications and improved long-term health of the mother and child. Ultrasound Elastography (USE) and Magnetic Resonance Elastography (MRE) provide means to evaluate tissue stiffness in utero. In conjunction with measures of vascular anatomy and perfusion, we can test mechanistic hypotheses about the relationship with anatomical function and deviations associated with disease states. For example, The Parker Hypothesis (Parker, Phys. Med. Biol. 59: 4443,14) proposes that viscoelastic measures of soft tissue stiffness are related to the fractal branching properties of the vascular anatomy. Methods: Term human placentae were obtained immediately upon delivery and evaluated directly either in a 3T GE MRI with Elastography or using a Siemens Antares US scanner and VF10-5 Probe with custom single track location shear wave elasticity imaging pulse sequences and accelerated processing. Other placentae were perfused through the umbilical cord and imaging, Doppler measures and elastography were conducted. At the end of the experiments, a barium gel was infused to enhance subsequent CT imaging of the fetal vasculature. Results: The utility of elastography in functional evaluation of the placenta are readily demonstrated in the following examples: 1) Placental tissue anomalies (e.g., infarcted areas) are stiff, and provided dramatic examples of the sensitivity USE and MRE methodologies for the detection of placental pathology; 2) Ex vivo placental perfusions have been used to relate placental stiffness to fetal vasculature when measured by USE, as seen when fetal vascular dynamics were pharmacologically manipulated. Clinical and high-resolution microCT systems can and have been used on placentae to provide additional post-delivery anatomical characterization and quantification of the vascular beds. These CT observations provide confirmation of in vivo Doppler US and the potential use of MR angiography for vascular characterization. We demonstrated that these datasets are amenable to automated identification and characterization of branching morphology, including centerline tree and Sholl analyses. Conclusion: These USE and MRE technologies enable promising new approaches for the prediction of risks during and after pregnancy. (Support: Goode Foundation) MRI localization of a placental infarct with associated elastographic ortho slice A: gross examination of placental lesion. B, MR segmented volume. C. Superimposed MRE. Yellow arrow directs attention to lesion.

Contralateral eye-to-eye comparison of intravitreal ranibizumab and a sustained-release dexamethasone intravitreal implant in recalcitrant diabetic macular edema.

ObjectiveTo compare the effects of intravitreal ranibizumab (RZB) or dexamethasone (DEX) intravitreal implant in cases of recalcitrant diabetic macular edema (DME).MethodsRetrospective, interventional study examining patients with symmetric bilateral, center-involved DME recalcitrant to treatment with RZB, who received DEX in one eye while the contralateral eye continued to receive RZB every 4–5 weeks for a study period of 3 months.ResultsEleven patients (22 eyes) were included: mean logarithm of the minimal angle of resolution (logMAR) visual acuity (VA) for the DEX arm improved from 0.415 (standard deviation [SD] ±0.16) to 0.261 (SD ±0.18) at final evaluation, and mean central macular thickness (CMT) improved from 461 µm (SD ±156) to 356 µm (SD ±110; net decrease: 105 µm, P=0.01). Mean logMAR VA for the RZB arm improved from 0.394 (SD ±0.31) to 0.269 (SD ±0.19) at final evaluation. Mean CMT improved from 421 µm (SD ±147) to 373 µm (SD ±129; net decrease: 48 µm, P=0.26).ConclusionA subset of recalcitrant DME patients demonstrated significant CMT reduction and VA improvement after a single DEX injection.

RO-06INCIDENCE OF CATARACT DEVELOPMENT IN PEDIATRIC PATIENTS RECEIVING CRANIOSPINAL IRRADIATION

RO-06. INCIDENCE OF CATARACT DEVELOPMENT IN PEDIATRIC PATIENTS RECEIVING CRANIOSPINAL IRRADIATION Ros Whelan, Todd Hankinson, Kathleen Dorris, Benjamin Saccomano, Michael Handler, Arthur Liu, Molly Hemenway, and Jennifer Madden; Children’s Hospital Colorado, Aurora, CO, USA OBJECTIVE: Craniospinal irradiation (CSI) is an important component of therapy for some children with brain tumors. CSI has been associated with numerous late effects, but there is a paucity of data regarding cataract development following CSI. We investigated the incidence of cataracts in children treated at our institution. METHODS: Single center retrospective analysis of children with primary intracranial neoplasms who received CSI between 07/2007 and 06/2015. Data included tumor histologyand location, radiation dose, cataract development and intervention. RESULTS: Sixty-five children received CSI over that time period (57 embryonal tumors, 5 germ cell tumors, 3 pineal tumors) and 46 had eye exams. Median CSI dose was 23.4 Gy (range 12 36 Gy). With a median follow up of 25.0 months, thirteen (28%) developed cataracts with a median time to develop cataracts of 27.6 months (range 20-60 months). Six have required intervention. CONCLUSIONS: Development of cataracts is a significant risk in children who require CSI for the treatment of a brain tumor. Routine eye exams should be included with long term follow-up. Further study will better delineate risk factors for the development of cataracts, allowing appropriate screening and management for these patients. Neuro-Oncology 18:iii159–iii164, 2016. doi:10.1093/neuonc/now082.6 #The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

LG-16RADIOGRAPHIC AND OPHTHALMOLOGIC CHARACTERISTICS OF OPTIC PATHWAY GLIOMA IN CHILDREN WITH NEUROFIBROMATOSIS 1

LG-16. RADIOGRAPHIC AND OPHTHALMOLOGIC CHARACTERISTICS OF OPTIC PATHWAY GLIOMA IN CHILDREN WITH NEUROFIBROMATOSIS 1 Elizabeth Unterbrink1, Benita Tamrazi1,2, Mark Borchert1,2, Ashley Margol1,2, Linda Randolph1,2, Tena Rosser1,2, Girish Dhall1,2, and Nathan Robison1,2; Children’s Hospital Los Angeles, Los Angeles, CA, USA; University of Southern California Keck School of Medicine, Los Angeles, CA, USA OBJECTIVE: To describe the natural history of optic pathway glioma (OPG) in children with neurofibromatosis 1 (NF1). METHODS: The Children’s Hospital Los Angeles (CHLA) institutional review board approved this retrospective study. Using a clinical database, we identified children with NF1 and OPG followed at CHLAwith at least 1 MRI obtained at ,12 years of age from 6/1/1997-5/31/2014. Demographic, treatment, and visual field/ acuity data were extracted. MRIs were reviewed by a neuroradiologist. RESULTS: Of 63 children with NF1 and OPG, 50 had available imaging and were included. Mean age at initial MRI was 4.8 years; mean follow-up was 6.8 years. OPG was apparent on brain MRI in 4/7 children at ,2 years (57%; 95% confidence interval[95%CI] 20-94); 19/23 by 4 years (83%; 95%CI 67-98); 29/31 by 6 years (94%; 95%CI 85-100); and 50/50 by 12 years. Among 13 children (26%) who subsequently received tumor-directed treatment, OPG was MRI-apparent in 5/6 children by 4 years (83%; 95%CI 54-100), 8/9 by 6 years (89%; 95%CI 68-100) and 13/13 by 8 years. Among children with detailed visual outcome data, visual impairment was seen in 6/20 at , 4 years (30%; 95%CI 10-50); and 26/45 by 12 years (58%; 95%CI 43-72). A subset had normalization of vision, with persistent visual abnormalities in only 14/41 children on follow-up (34%; 95%CI 20-49). DISCUSSION: A minority of children without MRI-apparent OPG at initial evaluation eventually developed symptomatic disease. The high incidence of early-onset visual abnormalities highlights the importance of early NF1 diagnosis and ophthalmologic screening. Neuro-Oncology 18:iii78–iii96, 2016. doi:10.1093/neuonc/now075.16 #The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Fixed-site high-frequency transcutaneous electrical nerve stimulation for treatment of chronic low back and lower extremity pain.

ObjectiveThe objective of this study was to determine if fixed-site high-frequency transcutaneous electrical nerve stimulation (FS-TENS) is effective in treating chronic low back and lower extremity pain.BackgroundTranscutaneous electrical nerve stimulation is widely used for treatment of chronic pain. General-purpose transcutaneous electrical nerve stimulation devices are designed for stimulation anywhere on the body and often cannot be used while the user is active or sleeping. FS-TENS devices are designed for placement at a pre-determined location, which enables development of a wearable device for use over extended time periods.MethodsStudy participants with chronic low back and/or lower extremity pain self-administered an FS-TENS device for 60 days. Baseline, 30-, and 60-day follow-up data were obtained through an online questionnaire. The primary outcome measure was the patient global impression of change. Pain intensity and interference were assessed using the Brief Pain Inventory. Changes in use of concomitant pain medications were evaluated with a single-item global self-rating.ResultsOne hundred and thirty participants were enrolled, with 88 completing the 60-day follow-up questionnaire. Most participants (73.9%) were 50 years of age or older. At baseline, low back pain was identified by 85.3%, lower extremity pain by 71.6%, and upper extremity pain by 62.5%. Participants reported widespread pain, at baseline, with a mean of 3.4 (standard deviation 1.1) pain sites. At the 60-day follow-up, 80.7% of participants reported that their chronic pain had improved and they were classified as responders. Baseline characteristics did not differentiate non-responders from responders. There were numerical trends toward reduced pain interference with walking ability and sleep, and greater pain relief in responders. There was a large difference in use of concomitant pain medications, with 80.3% of responders reporting a reduction compared to 11.8% of non-responders.ConclusionFS-TENS is a safe and effective option for treating chronic low back and lower extremity pain. These results motivate the use of FS-TENS in development of wearable analgesic devices.

The Development and Initial Assessment of a Novel Heart Rate Training Formula

The Development and Initial Assessment of a Novel Heart Rate Training Formula

NTCT-11WERNICKE ENCEPHALOPATHY IN CANCER PATIENTS: A LITERATURE REVIEW

NTCT-11. WERNICKE ENCEPHALOPATHY IN CANCER PATIENTS: A LITERATURE REVIEW Fernanda Wajnsztajn, Lauren Cameron, Gurcharanjeet Kaur, and Agnieszka Kowalska; Stony Brook Medicine, Stony Brook, NY, USA OBJECTIVE: To assess the frequency of Wernicke Encephalopathy (WE) in cancer patients and to determine if prophylaxis with thiamine prevents neurologic complications. BACKGROUND: Wernicke’s Encephalopathy (WE) is a known neurologic complication in cancer patients due to suspected etiologies such as chronic malnutrition, chemotherapy-associated vomiting, and thiamine consumption by rapidly growing tumors. MRI brain is considered the most valuable method to confirm the diagnosis. Currently amongst the cancer population there is no standardized approach to obtain thiamine levels,brainMRI, thiamine doseandduration,andwhen to initiateprophylaxis. METHODS: We utilized the search engine PubMed to review a total of 78 cases reported between 1990-2015. Patients with history of alcoholism were excluded from our review. RESULTS: The most common types of cancer associatedwith WE were gastrointestinal tract (35.6%) followedbyhematopoietic cancers (34.6%), gynecological cancers (9%), CNS cancers and head and neck gynecological cancers (6.4% each) and others (7.6%). WE was also frequently seen in patients treated with; antimetabolites (29.48%), followed by alkylating and anthracyclines agents (24.3% each), and Mitotic inhibitors (6.4%). Of the 78 cases reviewed 61.5% were females, with mean age of 44. Brain MRIs were obtained in 78% of patients, of those 93% revealed positive radiological findings. 76.9% of patients received thiamine, despite only 24% that had serum thiamine levels checked. 70.5% showed partial or total recovery after thiamine supplementation. The thiamine doses were variable and not frequently reported. Total parental nutrition was reported in 46.1% of patients. CONCLUSION: WE needs to be considered in all cancer patients, especially GI and hematopoietic cancers. Work up should consist of thiamine levels and MRI brain. Thiamine supplementation should be reinforced amongst patients receiving TPN. We recommend standardized WE prophylaxis in cancer patients in order to prevent neurologic complications. Neuro-Oncology 17:v172–v175, 2015. doi:10.1093/neuonc/nov226.11 Published by Oxford University Press on behalf of the Society for Neuro-Oncology 2015.

Assaying the enhancer landscape during early placental development to identify a trophoblast invasion transcriptional code and gene-enhancer network

Assaying the enhancer landscape during early placental development to identify a trophoblast invasion transcriptional code and gene-enhancer network

The efficacy and safety of adalimumab in ocular inflammatory disease

The efficacy and safety of adalimumab in ocular inflammatory disease Cheryl A Arcinue,1,2 Khayyam Durrani,1&ndash;3 Pichaporn Artornsombudh,1,2 Alaa Radwan,1,2 Ravi Parikh,1,2 Ana M Suelves,1,2 Sana S Siddique,1,2 Ian Chang,1,2 Janine M Preble,1,2 Charles Stephen Foster1&ndash;3 1Massachusetts Eye Research and Surgery Institution, 2Ocular Immunology and Uveitis Foundation, Cambridge, 3Department of Ophthalmology, Harvard Medical School, Boston, MA, USA Objective: To evaluate the efficacy and safety of adalimumab in the management of ocular inflammation at our institution. Methods: We performed a review of all patients with active ocular inflammation treated with adalimumab at our institution. Results: Seventy eyes of 49 patients were reviewed. The mean duration of follow-up was 19.6 months. Therapy with an average of 2.1 immunomodulatory agents had been attempted prior to adalimumab therapy. At 1-year follow-up, adalimumab was effective in achieving quiescence in 33 eyes (47%). The most common side effects were injection-site reactions, arthralgias, and nausea, occurring in two patients each. Adalimumab was discontinued due to side effects in 12 patients. Conclusion: These results suggest that adalimumab is an effective and safe therapeutic modality in ocular inflammation. Keywords: uveitis, biologic response modifier, TNF-&alpha;, adverse effects, therapeutic outcomes, scleritis, peripheral ulcerative keratitis

Incidental retinal vascular occlusions on hydroxychloroquine screening in patients with systemic lupus erythematosus

Incidental retinal vascular occlusions on hydroxychloroquine screening in patients with systemic lupus erythematosus Asima Bajwa,1 Gitanjali Khurana,2 Donald Kimpel,2 Ashvini K Reddy1 1Department of Ophthalmology, University of Virginia, Charlottesville, VA, USA; 2Division of Clinical Rheumatology, Department of Internal Medicine, University of Virginia, Charlottesville, VA, USA Objective: The proportion of patients with systemic lupus erythematosus (SLE) who manifest retinal involvement increases many fold in patients with active systemic disease. The objective of this report is to stress upon the significance of comprehensive ophthalmic assessment of all SLE patients to prevent and manage blinding ocular manifestations of the disease. Methods: Retrospective case review. Results: Incidental retinal vascular complications seen in patients undergoing baseline hydroxychloroquine screening. Conclusion: The purpose of comprehensive ophthalmic screening in SLE patients is twofold. It will aid in the diagnosis and treatment of blinding ocular complications of the disease and monitor hydroxychloroquine macular toxicity. Keywords: systemic lupus erythematosus, hydroxychloroquine, retinal vein occlusion, retinal artery occlusion

Validation of algorithms to detect distant metastases in men with prostate cancer using routine registry data in Denmark

ObjectiveAmong patients with prostate cancer, diagnostic codes for bone metastases in the Danish National Registry of Patients have a sensitivity of 44%. In an attempt to improve the sensitivity of registry-based identification of metastases from prostate cancer, we tested a series of algorithms, combining elevated prostate-specific antigen (PSA) levels, use of antiresorptive therapy, and performed bone scintigraphy.Patients and methodsWe randomly selected 212 men diagnosed with prostate cancer in 2005–2010 in the Central Denmark Region with prespecified PSA values, antiresorptive therapy, and bone scintigraphy who did not have a registry-based diagnostic code indicating presence of distant metastases. We defined three candidate algorithms for bone metastases: 1) PSA >50 μg/L and bone scintigraphy, 2) PSA >50 μg/L and antiresorptive therapy, and 3) PSA ≤50 μg/L with antiresorptive therapy or bone scintigraphy. An algorithm for distant metastasis site other than bone was defined as PSA >50 μg/L alone. Medical chart review was used as the reference standard to establish the presence or absence of metastases. Validity was expressed as a positive predictive value (PPV) or a negative predictive value, based on whether the algorithms correctly classified metastases compared with the reference standard.ResultsWe identified 113 men with evidence of metastases according to the candidate algorithms, and 99 men without evidence of metastases according to the candidate algorithm. The PPVs of PSA >50 μg/L were 0.10 (95% confidence interval [CI] 0.04–0.19) for bone metastases and 0.14 (95% CI 0.07–0.24) for nonbone metastases, regardless of receipt of antiresorptive therapy or presence of bone scintigraphy. The PPVs for any metastases were 0.16 (95% CI 0.06–0.32) for PSA >50 μg/L and 0.28 (95% CI 0.14–0.47) for PSA >50 μg/L with bone scintigraphy. Adding antiresorptive treatment to the algorithm did not improve PPV. All negative predictive values approached 1.00.ConclusionAlgorithms based on elevated PSA, antiresorptive therapy, or bone scintigraphy are not suitable for supplementing diagnostic codes to identify additional cases of distant metastases among men with prostate cancer. However, it is possible that in this setting, medical chart review is not a gold standard to identify metastases.

Catatonia in Down syndrome; a treatable cause of regression.

Objective:The main aim of this case series report is to alert physicians to the occurrence of catatonia in Down syndrome (DS). A second aim is to stimulate the study of regression in DS and of catatonia. A subset of individuals with DS is noted to experience unexplained regression in behavior, mood, activities of daily living, motor activities, and intellectual functioning during adolescence or young adulthood. Depression, early onset Alzheimer’s, or just “the Down syndrome” are often blamed after general medical causes have been ruled out. Clinicians are generally unaware that catatonia, which can cause these symptoms, may occur in DS.Study design:Four DS adolescents who experienced regression are reported. Laboratory tests intended to rule out causes of motor and cognitive regression were within normal limits. Based on the presence of multiple motor disturbances (slowing and/or increased motor activity, grimacing, posturing), the individuals were diagnosed with unspecified catatonia and treated with anti-catatonic treatments (benzodiazepines and electroconvulsive therapy [ECT]).Results:All four cases were treated with a benzodiazepine combined with ECT and recovered their baseline functioning.Conclusion:We suspect catatonia is a common cause of unexplained deterioration in adolescents and young adults with DS. Moreover, pediatricians and others who care for individuals with DS are generally unfamiliar with the catatonia diagnosis outside schizophrenia, resulting in misdiagnosis and years of morbidity. Alerting physicians to catatonia in DS is essential to prompt diagnosis, appropriate treatment, and identification of the frequency and course of this disorder.

Parental celiac disease and risk of asthma in offspring: a Danish nationwide cohort study.

ObjectiveThe incidences of celiac disease (CD) and asthma are increasing and the two conditions are associated in individuals. Risk of asthma may be passed on to the next generation through shared risk factors. We examined whether parental CD is associated with risk of asthma in offspring.MethodsWe conducted a population-based Danish nationwide cohort study, using medical databases, covering the period 1 January 1979 to 31 December 2009. For each child with a parental history of CD, we randomly sampled 100 children without this history from the children born in the same calendar year. We used Cox proportional-hazards regression to estimate incidence rate ratios for asthma, adjusting for measured covariates.ResultsWe identified 1,107 children with a parental history of CD and 110,700 children without this parental history. During up to 32 years of follow-up, 6,125 children received a hospital diagnosis of asthma. The adjusted incidence rate ratio for asthma associated with a parental history of CD was 1.09 (95% confidence interval: 0.86–1.39) and was similar for maternal and paternal CD. Inclusion of asthma-medication in the definition of asthma did not substantially change the results.ConclusionThere was no convincing evidence of an increased risk of asthma among offspring of parents with CD.

Blunt scissors stromal dissection technique for&amp;nbsp;deep anterior lamellar keratoplasty

ObjectiveWe describe a modified technique for performing lamellar dissection in deep anterior lamellar keratoplasty after failure to achieve a “big bubble” detachment of Descemet’s membrane (DM) with deep intrastromal pneumatic injection.MethodsThe technique utilizes blunt lamellar dissection with blunt-tipped corneal mini scissors as an alternative to a crescent blade, which can be difficult for surgeons to master and is associated with a high risk of perforation.ResultsOther techniques of blunt dissection, such as the Melles technique, cannot be utilized after failure to achieve a big bubble, as emphysema in the stroma prevents visualization of the spatula. In contrast, our blunt scissors lamellar dissection technique takes advantage of the emphysema and microdetachments of DM created by the pneumatic injection.ConclusionThis technique provides deep anterior lamellar keratoplasty surgeons with a simple, alternative method of baring DM or achieving a pre-DM plane with minimal residual stroma, after failure to achieve a big bubble.

Efficacy of the small molecule inhibitor of Lipid II BAS00127538 against Acinetobacter baumannii.

ObjectiveTo test the activity of a small molecule compound that targets Lipid II against Acinetobacter baumannii.MethodsSusceptibility to small molecule Lipid II inhibitor BAS00127538 was assessed using carbapenem- and colistin-resistant clinical isolates of A. baumannii. In addition, synergy between colisitin and this compound was assessed.ResultsSmall molecule Lipid II inhibitor BAS00127538 potently acts against A. baumannii and acts synergistically with colistin.ConclusionFor the first time, a compound that targets Lipid II is described that acts against multi-drug resistant isolates of A. baumannii. The synergy with colistin warrants further lead development of BAS00127538.

Fasinumab (REGN475), an antinerve growth factor monoclonal antibody, for the treatment of acute sciatic pain: results of a proof-of-concept study.

ObjectiveTo evaluate the efficacy and safety of subcutaneously administered fasinumab (REGN475), a nerve growth factor-neutralizing antibody, in patients with acute sciatic pain receiving standard of care therapy.MethodsThis was a double-blind, parallel-group, proof-of-concept study. Patients with unilateral, moderate-to-severe sciatic pain of 2–16 weeks’ duration were randomized to a subcutaneous dose of placebo (n=51), fasinumab 0.1 mg/kg (n=53), or 0.3 mg/kg (n=53); follow-up was 12 weeks. Pain was assessed in a daily diary using a numerical rating scale (NRS) (0= no pain, 10= worst pain) for average and worst leg and back pain. The primary efficacy end point was the area under the curve of NRS scores for average leg pain from baseline to week 4. Key secondary end points included changes in average and worst leg and back pain from baseline to the end of week 4 and to each weekly study visit. Patient functioning (Oswestry Disability Index) and concomitant analgesic use were also assessed. Safety and tolerability were evaluated by treatment-emergent adverse events (TEAEs).ResultsDemographic and clinical characteristics were similar among the treatment groups; 141 (88.7%) patients completed the study. For the primary end point, mean ± standard deviation area under the curve values from baseline to week 4 were not significantly different between placebo (96.8±6.0) and fasinumab 0.1 mg/kg (112.7±58.3; P=0.0610) or fasinumab 0.3 mg/kg (112.4±55.8; P=0.0923). All secondary efficacy end points of changes in pain and function demonstrated responses that were similar between placebo and fasinumab groups. Incidence of TEAEs was 45.1%, 50.9%, and 64.8% in the placebo, fasinumab 0.1mg/kg, and fasinumab 0.3 mg/kg groups, respectively. The most commonly reported TEAEs included paresthesia, arthralgia, pain in extremity, and headache.ConclusionAdministration of fasinumab provided no significant clinical benefit compared with placebo for the pain or functional limitations associated with acute sciatica. Fasinumab was generally well tolerated and incidence of TEAEs appeared to be dose related.