bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of Comedication on Levetiracetam Pharmacokinetics
Authors: Aldaz Azucena , Alzueta Natalia , Viteri César 
Published: November 2017

Background:
To evaluate the effect of concomitant antiepileptic therapy on levetiracetam (LEV) pharmacokinetics.

Methods:
A 6-year retrospective observational study. Patients were grouped according to the antiepileptic drug used as concomitant medication: group A, LEV in monotherapy; group B, LEV + enzyme-inducing antiepileptic drugs (EIAEDs); and group C, LEV + non–enzyme-inducing antiepileptic drugs (NEIAEDs). Apparent oral levetiracetam clearance (LEV CL/F) and basal serum levetiracetam concentrations (LEV C0) were compared among the different groups by analysis of variance.

Results:
A total of 330 LEV C0 corresponding to 205 patients (56% men) were identified. The mean (±SD) of LEV CL/F in group A (n = 180), B (n = 92), and C (n = 58) was 4.41 ± 2.06 L/h, 7.23 ± 3.72 L/h, and 4.87 ± 1.65 L/h, respectively. EIAEDs increased LEV CL/F (L/h) by 64% compared with the monotherapy group and by 48% compared with the NEIAEDs group. The greatest induction in LEV CL/F, compared with the LEV monotherapy group, was observed with carbamazepine, followed by oxcarbazepine and phenobarbital, and was increased by 81%, 64%, and 44%, respectively. LEV C0 values were significantly lower in the EIAEDs group than in the monotherapy group (17.30 ± 7.77 versus 20.08 ± 9.69 mcg/mL; P = 0.038) or indeed the NEIAEDs group (17.30 ± 7.77 versus 20.49 ± 9.46 mcg/mL; P = 0.027).

Conclusions:
Comedication with EIAEDs increased LEV CL/F by more than 40%, whereas carbamazepine had the greatest inducing potency with LEV CL/F being 81% higher than that of the monotherapy group. These data suggest that monitoring LEV serum concentration during polytherapy with EIAEDs is indicated.
Therapeutic Drug Monitoring of Asparaginase Activity—Method Comparison of MAAT and AHA Test Used in the International AIEOP-BFM ALL 2009 Trial
Authors: Lanvers-Kaminsky Claudia , Rüffer Andrea , Würthwein Gudrun , Gerss Joachim , Zucchetti Massimo , Ballerini Andrea , Attarbaschi Andishe , Smisek Petr , Nath Christa , Lee Samiuela , Elitzur Sara , Zimmermann Martin , Möricke Anja , Schrappe Martin , Rizzari Carmelo , Boos Joachim 
Published: November 2017

Background:
In the international AIEOP-BFM ALL 2009 trial, asparaginase (ASE) activity was monitored after each dose of pegylated Escherichia coli ASE (PEG-ASE). Two methods were used: the aspartic acid β-hydroxamate (AHA) test and medac asparaginase activity test (MAAT). As the latter method overestimates PEG-ASE activity because it calibrates using E. coli ASE, method comparison was performed using samples from the AIEOP-BFM ALL 2009 trial.

Methods:
PEG-ASE activities were determined using MAAT and AHA test in 2 sets of samples (first set: 630 samples and second set: 91 samples). Bland–Altman analysis was performed on ratios between MAAT and AHA tests. The mean difference between both methods, limits of agreement, and 95% confidence intervals were calculated and compared for all samples and samples grouped according to the calibration ranges of the MAAT and the AHA test.

Results:
PEG-ASE activity determined using the MAAT was significantly higher than when determined using the AHA test (P < 0.001; Wilcoxon signed-rank test). Within the calibration range of the MAAT (30–600 U/L), PEG-ASE activities determined using the MAAT were on average 23% higher than PEG-ASE activities determined using the AHA test. This complies with the mean difference reported in the MAAT manual. With PEG-ASE activities >600 U/L, the discrepancies between MAAT and AHA test increased. Above the calibration range of the MAAT (>600 U/L) and the AHA test (>1000 U/L), a mean difference of 42% was determined. Because more than 70% of samples had PEG-ASE activities >600 U/L and required additional sample dilution, an overall mean difference of 37% was calculated for all samples (37% for the first and 34% for the second set).

Conclusions:
Comparison of the MAAT and AHA test for PEG-ASE activity confirmed a mean difference of 23% between MAAT and AHA test for PEG-ASE activities between 30 and 600 U/L. The discrepancy increased in samples with >600 U/L PEG-ASE activity, which will be especially relevant when evaluating high PEG-ASE activities in relation to toxicity, efficacy, and population pharmacokinetics.
The Effect of Aromatherapy on Sleep Quality of Elderly People Residing in a Nursing Home
Authors: Faydalı Saide , Çetinkaya Funda 
Published: November 2017

Background:
Sleep is important for health and quality of life in the elderly, and sleep disturbances are reported to be associated with many of the adverse medical conditions.

Purpose:
This research was carried out to evaluate the effect of inhalation of lavender oil on sleep quality of nursing home residents.

Methods:
A questionnaire was used to evaluate sociodemographic characteristics and sleeping properties of the 30 volunteers, enrolled. Pittsburgh Sleep Quality Index was applied as a pre- and posttest to measure sleep quality of individuals who inhaled lavender oil drops on the pillows every evening for a week before sleeping.

Results:
Before and after aromatherapy, the mean Pittsburgh Sleep Quality Index score of the nursing home residents was

JOURNAL/honup/04.03/00004650-201801000-00003/3FSM1/v/2023-09-12T063022Z/r/image-gif

= 6.0 ± 5.1 and

JOURNAL/honup/04.03/00004650-201801000-00003/3FSM1/v/2023-09-12T063022Z/r/image-gif

= 2.6 ± 3.4, respectively, whereas statistically significant difference was not observed for independent variables. Cronbach α reliability coefficient of the Pittsburgh Sleep Quality Index scale was found to be 0.816.

Conclusions/Implications for Practice:
The results indicated an improvement of sleep quality of nursing home residents after the application of aromatherapy with lavender oil.
COMBINED AUTOLOGOUS TRANSPLANTATION OF NEUROSENSORY RETINA, RETINAL PIGMENT EPITHELIUM, AND CHOROID FREE GRAFTS
Authors: Parolini Barbara , Grewal Dilraj S. , Pinackatt Sajish J. , Baldi Andrea , Di Salvatore Attilio , Besozzi Gianluca , Finzi Alessandro , Cardillo Daniele , Mahmoud Tamer H. 
Published: November 2017

Purpose:
To evaluate the feasibility and initial functional and anatomical outcomes of transplanting a full-thickness free graft of choroid and retinal pigment epithelium (RPE), along with neurosensory retina in advanced fibrosis and atrophy associated with end-stage exudative age-related macular degeneration with and without a concurrent refractory macular hole.

Methods:
During vitrectomy, an RPE–choroidal and neurosensory retinal free graft was harvested in nine eyes of nine patients. The RPE–choroidal and neurosensory retinal free graft was either placed subretinally (n = 5), intraretinally to cover the foveal area inside an iatrogenically induced macular hole over the RPE–choroidal graft (n = 3) or preretinally (n = 1) without a retinotomy wherein both free grafts were placed over the concurrent macular hole. Silicone oil endotamponade was used in all cases.

Results:
Mean follow-up was 7 ± 5.5 months (range 3–19). The mean preoperative visual acuity was ∼count fingers (logarithm of the minimum angle of resolution = 2.11, range 2–3), which improved to ∼20/800 (logarithm of the minimum angle of resolution 1.62 ± 0.48, range 0.7–2, P = 0.04). Vision was stable in 5 eyes (55.6%) and improved in 4 eyes (44.4%). Reading ability improved in 5 eyes (55.6%). Postoperative complications were graft atrophy (n = 1), epiretinal membrane (n = 1), and dislocation of neurosensory retina–choroid–RPE free graft (n = 1).

Conclusion:
Combined autologous RPE–choroid and neurosensory retinal free graft is a potential surgical alternative in eyes with end-stage exudative age-related macular degeneration, including concurrent refractory macular hole.
COMPARISON OF 3 MM × 3 MM VERSUS 6 MM × 6 MM OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY SCAN SIZES IN THE EVALUATION OF NON–PROLIFERATIVE DIABETIC RETINOPATHY
Authors: Ho Joseph , Dans Kunny , You Qisheng , Nudleman Eric D. , Freeman William R. 
Published: November 2017

Purpose:
To evaluate the utility of different optical coherence tomography angiography scan protocols in evaluating retinal changes in non–proliferative diabetic retinopathy.

Methods:
Patients were imaged with the RTVue XR Avanti OCT 3 mm × 3 mm and 6 mm × 6 mm “Angio Retina” scan protocols. Ability to clearly delineate the foveal avascular zone (FAZ), FAZ remodeling, microaneurysms, capillary nonperfusion, motion, and doubling artifacts were evaluated.

Results:
Forty-six eyes from 27 patients were enrolled. Eighty-nine percent of 3 mm × 3 mm versus 59% of 6 mm × 6 mm scans clearly delineated the FAZ (P = 0.001). Eighty percent of 3 mm × 3 mm versus 43% of 6 mm × 6 mm scans demonstrated FAZ remodeling (P = 0.0002). Microaneurysms were detected by 57% of 6 mm × 6 mm and 35% of 3 mm × 3 mm scans (P = 0.003). Capillary nonperfusion was detected in 87% of 3 mm × 3 mm scans versus 89% of 6 mm × 6 mm scans (P = 0.99). No significant differences were noted in the incidence of artifacts between the scan sizes (motion artifact P = 0.29 and doubling artifact P = 0.29).

Conclusion:
3 mm × 3 mm scan delineated FAZ and remodeling better than 6 mm × 6 mm scan, likely because of its higher scan density. 6 mm × 6 mm scans detected microaneurysms more readily than 3 mm × 3 mm, likely because of its larger scan area. There were utility for both 3 mm × 3 mm and 6 mm × 6 mm scans when evaluating these patients.
APOPTOSIS AND ANGIOFIBROSIS IN DIABETIC TRACTIONAL MEMBRANES AFTER VASCULAR ENDOTHELIAL GROWTH FACTOR INHIBITION
Authors: Jiao Chunhua , Eliott Dean , Spee Christine , He Shikun , Wang Kai , Mullins Robert F. , Hinton David R. , Sohn Elliott H. 
Published: November 2017

Purpose:We sought to characterize the angiofibrotic and apoptotic effects of vascular endothelial growth factor (VEGF)-inhibition on fibrovascular epiretinal membranes in eyes with traction retinal detachment because of proliferative diabetic retinopathy.Methods:Membranes were excised from 20 eyes of 19 patients (10 randomized to intravitreal bevacizumab, 10 controls) at vitrectomy. Membranes were stained with antibodies targeting connective tissue growth factor (CTGF) or VEGF and colabeled with antibodies directed against endothelial cells (CD31), myofibroblasts, or retinal pigment epithelium markers. Quantitative and colocalization analyses of antibody labeling were obtained through immunofluorescence confocal microscopy. Masson trichrome staining, cell counting of hematoxylin and eosin sections, and terminal dUTP nick-end labeling staining were performed.Results:High levels of fibrosis were observed in both groups. Cell apoptosis was higher (P= 0.05) in bevacizumab-treated membranes compared with controls. The bevacizumab group had a nonsignificant reduction in colocalization in CD31–CTGF and cytokeratin–VEGF studies compared with controls. Vascular endothelial growth factor in extracted membranes was positively correlated with vitreous levels of VEGF; CTGF in extracted membranes was negatively correlated with vitreous levels of CTGF.Conclusion:Bevacizumab suppresses vitreous VEGF levels, but does not significantly alter VEGF or CTGF in diabetic membranes that may be explained by high baseline levels of fibrosis. Bevacizumab may cause apoptosis within fibrovascular membranes.
INTERNAL LIMITING MEMBRANE PEELING IN MACULAR HOLE SURGERY; WHY, WHEN, AND HOW?
Authors: Chatziralli Irini P. , Theodossiadis Panagiotis G. , Steel David H. W. 
Published: November 2017

Purpose:
To review the current rationale for internal limiting membrane (ILM) peeling in macular hole (MH) surgery and to discuss the evidence base behind why, when, and how surgeons peel the ILM.

Methods:
Review of the current literature.

Results:
Pars plana vitrectomy is an effective treatment for idiopathic MH, and peeling of the ILM has been shown to improve closure rates and to prevent postoperative reopening. However, some authors argue against ILM peeling because it results in a number of changes in retinal structure and function and may not be necessary in all cases. Furthermore, the extent of ILM peeling optimally performed and the most favorable techniques to remove the ILM are uncertain. Several technique variations including ILM flaps, ILM scraping, and foveal sparing ILM peeling have been described as alternatives to conventional peeling in specific clinical scenarios.

Conclusion:
Internal limiting membrane peeling improves MH closure rates but can have several consequences on retinal structure and function. Adjuvants to aid peeling, instrumentation, technique, and experience may all alter the outcome. Hole size and other variables are important in assessing the requirement for peeling and potentially its extent. A variety of evolving alternatives to conventional peeling may improve outcomes and need further study.
RETINOBLASTOMA IN INDIA
Authors: Kaliki Swathi , Patel Anamika , Iram Sadiya , Ramappa George , Mohamed Ashik , Palkonda Vijay A. R. 
Published: November 2017

Purpose:To study the clinical presentation, treatment, and outcome of patients with retinoblastoma (RB) in India.Methods:Retrospective study of 1,457 patients with RB (2,074 eyes).Results:The mean age at presentation of RB was 29 months (median, 24 months; range, <1–370 months). There were 812 (56%) men and 645 (44%) women with unilateral presentation of RB in 57% (n = 834) and bilateral in 43% (n = 623). Familial RB was present in 4% (n = 55). The most common presenting complaints included leukocoria (n = 1,100; 75%), proptosis (n = 91; 6%), strabismus (n = 77; 5%), and red eye (n = 68; 5%). Most (n = 1,889; 91%) tumors were intraocular in location, and 185 (n = 185; 9%) had extraocular tumor extension at presentation. The most common modalities of primary treatment–included systemic chemotherapy (n = 1,171; 60%) and enucleation (n = 674; 35%). At a mean follow-up period of 44 months (median, 30 months; range, 3–234 months), 92% (n = 1,206) were alive, and 108 (8%) patients died because of RB. Based on Kaplan–Meier analysis, the survival at 1, 3, 5, and 10 years was 94%, 91%, 90%, and 89%, respectively.Conclusion:The most common presenting signs of RB in Asian Indian population are leukocoria and proptosis. With appropriate treatment, the survival rate is favorable at 92%.
Global burden of neuropathic pain
Authors: Blyth Fiona M. 
Published: December 2017

Abstract
Global burden of disease studies measure the impact of disability and premature death resulting from specific diseases and injuries. Recently, these studies have highlighted the leading contribution of regional pain conditions (low back pain and neck pain in particular) to the global burden of disability. However, to date, there has not been a systematic approach to measuring the global burden of disease attributable to neuropathic pain (NP) conditions. This article gives a brief overview of the concept of burden of disease, the underlying drivers, and dynamics of disease burden at a population level and proposes an agenda in relation to NP for developing the conceptual and empirical evidence base necessary for estimating the global burden of NP.
Prophylactic Use of Haloperidol and Changes in Glucose Levels in Hospitalized Older Patients
Authors: van Keulen Kris , Knol Wilma , Schrijver Edmée J.M. , van Marum Rob J. , van Strien Astrid M. , Nanayakkara Prabath W.B. 
Published: November 2017

Abstract

Background
Treatment with antipsychotic drugs has been associated with glucose dysregulation in older outpatients, especially in the early stage of therapy. The underlying mechanism is, however, unclear. The aim of this study was to investigate changes in glucose levels during haloperidol use compared with the use of placebo among older hospitalized patients.

Methods
This substudy was part of a larger multicenter, randomized, double blind, placebo-controlled clinical trial among hospitalized patients aged 70 years and older who had an increased risk of in-hospital delirium. Patients who were admitted to the Jeroen Bosch Hospital in 's-Hertogenbosch between June 2014 and February 2015 were invited to participate in the study. Participating patients were randomized for treatment and given 1 mg of haloperidol or a placebo twice daily for a maximum of 7 consecutive days (14 doses). Exclusion criteria for this substudy were the use of corticosteroids and changes in diabetes medication. Random blood samples to determine glucose levels were collected before day 1 and on day 6 of the study. Student independent sample t test was used to determine differences in glucose changes between both groups.

Results
Twenty-nine patients were included (haloperidol, n = 14; placebo, n = 15). The mean glucose level for placebo users was 139.3 mg/dL (SD, 50.1) on day 1 and 140.8 mg/dL (SD, 45.7) on day 6, and the mean glucose level for haloperidol users was 139.9 mg/dL (SD, 71.0) on day 1 and 150.2 mg/dL (SD, 39.1) on day 6. The difference was not statistically significant (P = 0.685).

Conclusions
Short-term prophylactic use of haloperidol was not associated with changes in glucose levels in older hospitalized patients compared with those given a placebo in this small study.
Isometric Exercise to Reduce Pain in Patellar Tendinopathy In-Season: Is It Effective “on the Road”?
Authors: Rio Ebonie , Purdam Craig , Girdwood Michael , Cook Jill 
Published: November 2017

Objective:
To investigate the effectiveness of an isometric squat exercise using a portable belt, on patellar tendon pain and function, in athletes during their competitive season.

Design:
Case series with no requirements to change any aspect of games or training. The object of this pragmatic study was to investigate this intervention in addition to “usual management.” A control or sham intervention was considered unacceptable to teams.

Setting:
In-season.

Participants:
A total of 25 male and female elite and subelite athletes from 5 sports.

Intervention:
5 × 30-second isometric quadriceps squat exercise using a rigid belt completed over a 4-week period.

Main Outcome Measures:
(1) single-leg decline squat (SLDS)—a pain provocation test for the patellar tendon (numerical rating score of pain between 0 and 10), (2) VISA-P questionnaire assessing patellar tendon pain and function, and (3) self-reported adherence with completing the exercise over a 4-week period.

Results:
Baseline SLDS pain was high for these in-season athletes, median 7.5/10 (range 3.5-9) and was significantly reduced over the 4-week intervention (P < 0.001, ES r = 0.580, median change 3.5). VISA-P scores improved after intervention (P < 0.001, ES r = 0.568, mean change 12.2 ± 8.9, percentage mean change 18.8%, where minimum clinical important difference of relative change for VISA-P is 15.4%-27%). Adherence was high; athletes reported completing the exercise 5 times per week.

Conclusions:
This pragmatic study suggests that a portable isometric squat reduced pain in-season for athletes with patellar tendinopathy (PT). This form of treatment may be effective, but clinical trials with a control group are needed to confirm the results.
Auditory Related Resting State fMRI Functional Connectivity in Tinnitus Patients: Tinnitus Diagnosis Performance
Authors: Minami Shujiro B. , Oishi Naoki , Watabe Takahisa , Uno Kimiichi , Ogawa Kaoru 
Published: November 2017

Objective:
The purpose of the present study was to investigate functional connectivity in tinnitus patients with and without hearing loss, and design the tinnitus diagnosis performance by resting state functional magnetic resonance imaging (rs-fMRI).

Subjects and Methods:
Nineteen volunteers with normal hearing without tinnitus, 18 tinnitus patients with hearing loss, and 11 tinnitus patients without hearing loss were enrolled in this study. The subjects were evaluated with rs-fMRI, and region of interests (ROIs) based correlation analyses were performed using the CONN toolbox version 16 and SPM version 8. The correlation coefficients from individual level results were converted into beta values.

Results:
With a beta threshold of more than 0.2, 91% of all possible connections between auditory-related ROIs (Heschl's gyrus, planum temporale, planum polare, operculum, insular cortex, superior temporal gyrus) in the control group remained intact, whereas 83 and 66% of such connections were present in the hearing loss and the normal-hearing tinnitus group. However, between non-auditory-related ROIs, the rates of intact connections at a beta threshold of more than 0.2 were 17% in the control group, and 16 and 15% in the tinnitus groups. When resting state fMRI positive is defined as less than 9% of all possible connections between auditory-related ROIs with a beta threshold of more than 0.7, the sensitivity and specificity of tinnitus diagnosis is 86 and 74%, respectively.

Conclusions:
The associations between auditory-related networks are weakened in tinnitus patients, even if they have normal hearing. It is possible that rs-fMRI can be a tool for objective examination of tinnitus, by focusing the auditory-related areas.
Survey of the American Neurotology Society on Cochlear Implantation: Part 1, Candidacy Assessment and Expanding Indications
Authors: Carlson Matthew L. , Sladen Douglas P. , Gurgel Richard K. , Tombers Nicole M. , Lohse Christine M. , Driscoll Colin L. 
Published: November 2017

Objective:
To examine practice variance of cochlear implant candidacy assessment and off-label indications across centers in the United States.

Methods:
Cross-sectional survey of the American Neurotology Society (ANS).

Results:
A total of 81 surveys were returned from ANS members who report regular involvement in cochlear implant care. Overall there was a broad distribution in age and clinical experience, with most respondents reporting ACGME accreditation in neurotology and employment at an academic center. The annual volume of cochlear implant surgeries varied considerably across centers.
Seventy-eight percent of respondents performed cochlear implantation for at least one of the following indications within the last 2 years: profound hearing loss in children less than 12 months of age (35, 43%), children with asymmetrical hearing loss where at least one ear was better than performance cutoff for age (25, 31%), adults with asymmetrical hearing where at least one ear was better than the performance cutoff for adult criteria (49, 61%), single-sided deafness (37, 46%), and ipsilateral vestibular schwannoma (28, 35%). Centers with a higher annual implant volume more frequently performed off-label implantation in all queried populations (all, p≤0.001), and performed surgery on infants with congenital deafness at a younger age (p = 0.013), compared with centers with lower surgical volume.
When surveyed regarding speech perception testing practices for adult candidacy assessment, 75 (100%) respondents who answered this question reported routine use of AzBio sentences, 42 (56%) CNC word scores, and 26 (35%) HINT testing; only 7 (9%) reported using BKB-SIN testing and 6 (8%) reported using CUNY scores. Fifty-one (68%) reported routine use of speech-in-noise testing to determine adult cochlear implant candidacy, 21 (28%) reported selective use only when patient scores were borderline in quiet, and 3 (4%) reported that their center does not currently use testing in noise for candidacy determination. Nineteen (26%) solely used +10 dB signal-to-noise ratio (SNR), 12 (16%) solely used +5 dB SNR, and 41 (55%) used both +10 and +5 dB SNR. Overall, 19% (N = 14) only perform unilateral implantation in the Medicare population, while 81% (N = 58) consider bilateral implantation.

Conclusion:
Significant variation in cochlear implant candidacy assessment and off-label implantation exists across centers and providers in the United States resulting in healthcare inequities. The high percentage of surgeons performing implantations for off-label or nontraditional indications reflects the overly restrictive and dated status of current implant guidelines. With greater adoption of more difficult speech perception testing in noise, careful clinical judgment is needed to maintain a favorable risk–benefit balance for prospective implant candidates.