bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low-Dose Medication and Long-Term Outcome in Myasthenia Gravis
Authors: Salins Salomi , Teter Barbara , Kavak Katelyn , Wolfe Gil I. , Silvestri Nicholas J. 
Published: November 2016

Abstract

Objectives:
Many advances have been made in the diagnosis, treatment, and management of myasthenia gravis (MG) and most patients will eventually progress to experience minimal manifestations (MM) of the disease or remission. However, there is a paucity of literature on medication dosing needed to achieve such a favorable clinical status in the long term. The objective of this article was to (1) study the course of MG and identify clinical predictors of maintenance of eventual disease remission or minimal manifestations and (2) determine if patients on low-dose medications have comparable MG Foundation of America (MGFA) scores and postintervention statuses (PIS) with those on conventional therapeutic dosing.

Methods:
This is a retrospective longitudinal chart review of 74 patients with MG. A subset of 28 of 74 patients diagnosed with MG after 2000 who were followed for at least 3 consecutive years from the year of diagnosis were also analyzed. An annual MGFA score, PIS, medication doses, and thymectomy status were obtained. Remission or MM of disease was defined as MGFA clinical classification <2 that persisted over the past 2 follow-up visits.

Results:
Thirty-four of 74 patients were on low-dose medications at last follow-up. There was no statistical difference between medication dosages and MGFA scores. In a subset of 28 patients, 23 (88.5%) with eventual disease remission or MM at last follow-up had an MGFA class <2 at their third year of diagnosis. In contrast, only 3 of 9 subjects with more symptomatic disease had similar results (P = 0.005). In terms of PIS at last follow-up, most patients were either in complete stable remission, pharmacologic remission, or MM status. Most patients (78.3%) had an MGFA class of 0 or 1 at last follow-up; 45% were on low-dose medications.

Conclusions:
Most patients with MG will realize disease stability characterized by either remission or MM status. A significant number of such patients were able to be maintained on low doses of medications to treat MG. The MGFA class at year 3 of diagnosis is a clinical predictor of long-term disease prognosis. There was no statistical difference between medication doses and MGFA scores at last follow-up.
Inclusion Body Myositis: What Most Impacts Patients' Lives
Authors: Gibson Cynthia , Johnson Nicholas E. , Eastwood Eileen , Heatwole Chad 
Published: November 2016

Abstract

Objective:
Inclusion body myositis (IBM) is the most common form of idiopathic inflammatory myopathy in adults older than 50 years. Few studies have focused on the functional, physical, and social limitations of this disease. This study identifies pertinent symptoms that impact the health and daily function of patients with IBM.

Methods:
We used semistructured interviews with 10 biopsy-confirmed adults with IBM to identify the psychological, physical, and functional limitations that have the greatest impact on the lives of patients with IBM.

Results:
Participants with IBM provided 644 direct quotes identifying issues that have the greatest effect on their lives. Two hundred nine individual symptoms and 17 symptomatic themes were identified by patients as having a significant impact on their lives. The symptomatic themes mentioned most frequently involved mobility and ambulation, emotional distress, and activity impairment.

Conclusions:
Identifying critical issues to patients with IBM is potentially useful for clinicians whose aim is to provide optimal care to patients with IBM.
Rapidly Resolving Weakness Related to Hypokalemia in Patients Infected With Dengue Virus
Authors: Maurya Pradeep K. , Kulshreshtha Dinkar , Singh Ajai K. , Thacker Anup K. 
Published: November 2016

Abstract

Objectives:
Dengue is a mosquito-borne disease caused by arbovirus and well known for its typical fever with thrombocytopenia syndrome. Acute hypokalemic quadriparesis is a rare presentation of dengue with uncertain pathogenesis. We aim to describe the clinical and biochemical characteristics of rapidly resolving weakness related to hypokalemia in patients infected with dengue virus.

Methods:
A retrospective review of the records of patients with diagnosis of dengue-associated hypokalemic weakness was performed. Demography, clinical, biochemical characteristics, and outcome of the patients were recorded during acute phase of illness.

Results:
Our study cohort comprised 12 patients and all were males from urban dwelling. The median age was 34.5 years (range, 18–50). Presentation was acute onset rapidly worsening pure motor quadriparesis preceded by short lasting febrile episode. Weakness ranged from 2/5 to 4/5 on Medical Research Council (MRC) scale with generalized hyporeflexia or areflexia. The baseline serum potassium was mean ± SD (2.7 ± 0.48 mmol/L). All patients showed elevation of liver transaminases and elevated creatine phosphokinase level. Weakness improved in 24–72 hours in all patients with correction of serum potassium.

Conclusions:
Dengue-associated acute hypokalemic paralysis is an underrecognized entity having favorable outcome. It should be suspected in patients presenting as acute pure motor quadriparesis after febrile illness in dengue endemic areas.
Dermal Titanium Dioxide Deposition Associated With Intralesional Triamcinolone Injection
Authors: Cohen Brandon E. , Bashey Sameer , Cole Christine , Abraham Jerrold L. , Ragsdale Bruce , Ngo Binh 
Published: November 2016

Abstract:
Cutaneous discoloration secondary to dermal deposition of titanium dioxide (TiO2) particles is recognized but seldom reported in the literature. In this report, the authors describe the case of a 61-year-old gentleman, with a long history of alopecia areata, who presented with numerous, discrete dark blue macules on the scalp. Scanning electron microscopy with energy dispersive x-ray spectroscopy analysis ultimately identified the macules as deposits of TiO2. The patient had a history of intralesional triamcinolone injections for management of alopecia areata. A sample of generic 0.1% triamcinolone acetonide paste was analyzed and found to contain many TiO2 particles analogous to those seen in the patient's biopsy sample. To the authors' knowledge, this is the first reported case of TiO2 deposition in the dermis likely resulting from topical combined with intralesional triamcinolone injection.
Development and Validation of a Simultaneous Quantification Method of 14 Tyrosine Kinase Inhibitors in Human Plasma Using LC-MS/MS
Authors: Huynh Huu H. , Pressiat Claire , Sauvageon Hélène , Madelaine Isabelle , Maslanka Patricia , Lebbé Céleste , Thieblemont Catherine , Goldwirt Lauriane , Mourah Samia 
Published: November 2016

Background:
A sensitive liquid chromatography coupled with tandem mass spectrometry (MS/MS) method for the analysis in a small volume of plasma of 14 tyrosine kinase inhibitors currently used (imatinib, dasatinib, ibrutinib, ponatinib, trametinib, sunitinib, cobimetinib, dabrafenib, erlotinib, lapatinib, nilotinib, bosutinib, sorafenib, and vemurafenib) has been developed and validated. This multianalyte liquid chromatography coupled with MS/MS assay is of interest for anticancer drug combination therapy.

Methods:
After a simple protein precipitation of plasma samples, the chromatographic separation was performed using an ultra performance liquid chromatography system coupled with MS/MS in a positive ionization mode. The mobile phase consisted of a gradient elution of 10 mmol/L formate ammonium buffer containing 0.1% (vol/vol) formic acid (phase A) and acetonitrile with 0.1% (vol/vol) formic acid (phase B) at a flow rate of 300 μL/min.

Results:
The analysis time was 5.0 minutes per run, and all analytes and internal standard eluted within 1.45–1.79 minutes. The calibration curves were linear over the range from 1 to 500 ng/mL for bosutinib, cobimetinib, dasatinib, ibrutinib, and trametinib, from 5 to 500 ng/mL for ponatinib and sunitinib; from 50 to 2500 ng/mL for lapatinib; from 750 to 100,000 ng/mL for vemurafenib, and from 10 to 2500 ng/mL for dabrafenib, erlotinib, imatinib, nilotinib, and sorafenib, with coefficients of correlation above 0.99 for all analytes. The intra- and interday imprecisions were below 14.36%.

Conclusions:
This method was successfully applied to therapeutic drug monitoring in clinical practice.
Prediction of an Optimal Dose of Aripiprazole in the Treatment of Schizophrenia From Plasma Concentrations of Aripiprazole Plus Its Active Metabolite Dehydroaripiprazole at Week 1
Authors: Nagai Goyo , Mihara Kazuo , Nakamura Akifumi , Nemoto Kenji , Kagawa Shoko , Suzuki Takeshi , Kondo Tsuyoshi 
Published: November 2016

Background:
It has been suggested that a plasma trough concentration of aripiprazole plus its active metabolite, dehydroaripiprazole of 225 ng/mL is a threshold for a good therapeutic response in the treatment of acutely exacerbated patients with schizophrenia. The present study investigated whether or not an optimal dose of aripiprazole could be predicted from these concentrations at week 1.

Methods:
The subjects were 26 inpatients with schizophrenia, who received aripiprazole once a day for 3 weeks. The daily doses were 12 mg for the first week and 24 mg for the next 2 weeks. No other drugs except biperiden and flunitrazepam were coadministered. Blood samples were taken at weeks 1 and 3 after the treatment. Plasma concentrations of aripiprazole and dehydroaripiprazole were measured using liquid chromatography with mass-spectrometric detection.

Results:
There was a significant linear relationship between the plasma concentrations of aripiprazole plus dehydroaripiprazole at weeks 1 (x) and 3 (y) (P < 0.001). Regression equation was y = 2.580x + 34.86 (R2 = 0.698). Based on the equation, a nomogram to estimate an optimal dose of aripiprazole could be constructed.

Conclusions:
The present study suggests that an optimal dose of aripiprazole for the treatment of patients with schizophrenia can be predicted from the plasma concentrations of the sum of the 2 compounds at week 1.
Peripheral Ulcerative Keratitis Secondary to Chronic Hepatitis B Infection
Authors: Wei David W. , Pagnoux Christian , Chan Clara C. 
Published: November 2016

Purpose:
To report a unique case of peripheral ulcerative keratitis secondary to hepatitis B virus (HBV)-associated cryoglobulinemia and vasculitis and its pharmacological and surgical treatment and 2-year follow-up.

Methods:
A 52-year-old woman presented with unilateral eye pain and photophobia, arthralgia, remnants of a maculopapular rash, and subsequently facial numbness several weeks later. Her best spectacle-corrected visual acuity (BSCVA) in the affected eye was 20/80. Slit-lamp examination revealed severe superior corneal thinning without infiltrate. Corneal ulceration worsened until 10% of the cornea remained. Laboratory workup was positive for rheumatoid factor and revealed significantly decreased C4 complement, and HBV serology was positive.

Results:
Clinical history, examinations, and laboratory results suggest HBV-associated cryoglobulinemia and vasculitis. Management included prednisone, cyclophosphamide, and mycophenolate mofetil for immunosuppression and tenofovir for HBV treatment. Conjunctival resection and a glue patch were used to reduce inflammation and stabilize corneal melt. BSCVA improved after treatment was initiated. Two years after initial presentation, her BSCVA is 20/30−2, significantly improved from her vision at presentation.

Conclusions:
Diagnosis of peripheral ulcerative keratitis requires thorough history and physical examinations given the numerous causes. Prompt treatment including immunosuppressive medication and, in this case, antiviral medication is crucial to preventing serious visual consequences including corneal perforation and blindness.
Long-Term Results for Entropion Repair by Tarsal Margin Rotation With Posterior Lamella Superadvancement
Authors: Russell David J. , Seiff Stuart R. 
Published: November 2016

Purpose:
To report the long-term stability of tarsal margin rotation and posterior lamellar superadvancement (TMR PLS) for the repair of upper eyelid cicatricial entropion.

Methods:
A retrospective chart review was performed from January 2000 through December 2014 to identify all patients who had TMR PLS at the authors’ institution. Charts were reviewed for demographic information, recurrence of entropion or trichiasis, and surgical complications. Failure was defined as return of entropion. Patients with greater than 24 months of follow up were included.

Results:
A total of 30 TMR PLS procedures were performed during the review period. Nineteen cases from 14 patients were included in the final analysis. None of the 19 cases demonstrated recurrence of entropion over an average follow-up period of 78.3 months. Eight cases demonstrated trichiasis after TMR PLS, 5 of which required treatment.

Conclusion:
This case series suggests that TMR PLS for the treatment of upper eyelid cicatricial entropion has excellent long-term stability.
The Latino Eyelid: Anthropometric Analysis of a Spectrum of Findings
Authors: Fry Constance L. , Naugle Thomas C. , Cole Shelley A. , Gelfond Jonathan , Chittoor Geetha , Mariani Angeline F. , Goros Martin W. , Haik Barrett G. , Voruganti Venkata Saroja 
Published: November 2016

Purpose:
Published anthropometric measurements of the Latino eyelid are limited. This study describes features spanning the morphologic range from non-Latino whites to East Asians in the spectrum of the Latino eyelid.

Methods:
A cross-sectional study of 68 people (32 Latinos, 18 non-Latino whites, and 18 East Asians, ages 18–39), approved by the Institutional Review Board and HIPAA-compliant, was performed. Saliva samples determined genetic components. Indirect anthropometric measurements were performed with ImageJ software. Eyelid measurements included margin reflex distance, palpebral fissure height, eyelid crease height, orbital height, horizontal fissure length, inner and outer canthal distances, medial and lateral canthal angles, and lateral canthal angle of inclination. Additionally, exophthalmometry and epicanthal folds were recorded.

Results:
Analysis of 184 markers from HumanExome Chip data revealed distinct clustering patterns. Genetically, the Asian participants were in 1 group, the whites in another group, and the Latinos spanned the spectrum between these 2 groups. In Latinos, the inner canthal distance and lateral canthal angle of inclination were similar to Asians, whereas the eyelid crease spanned the range from Asians to whites. Half of the Latinos had epicanthal folds.

Conclusions:
Latinos possess a spectrum of eyelid features spanning the morphologic characteristics from those of non-Latino whites to those of East Asians. These normative data on Latinos from Texas and Mexico aid in the diagnoses of Latino eyelid disorders and are a reference for optimizing oculofacial surgery outcomes.
Introducing copayments in the emergency department would deter appropriate visits in the Netherlands
Authors: Kraaijvanger Nicole , Rijpsma Douwe , van Leeuwen Henk , Edwards Michael 
Published: November 2016

Objective
To determine what the effects of introduction of copayments for self-referred emergency department (ED) visits would be in the Netherlands and at what amount patients would turn to a GP before visiting an ED.

Methods
This questionnaire study was carried out in the ED of the Rijnstate Hospital, a community teaching hospital in the Netherlands. In the Netherlands, a deductible excess system is in use and this study investigated the effects of a copayment for self-referred patients (SRPs) on top of the deductible excess. A questionnaire was developed and handed out to SRPs.

Results
A total of 433 SRPs were included; their average age was 33.1 years and 63% were male. With a copayment of €100, 47% of SRPs would choose to visit their GP instead of the ED. A further increase in the copayment amount is largely ineffective in reducing the number of self-referred ED visits. The higher the household income and education level and the more urgent the triage category, the larger the copayment patients are willing to pay. There is no significant relation between appropriateness and the amount of copayment that patients are willing to pay and we found no specific copayment level that resulted in reducing mainly inappropriate ED visits.

Conclusion
With a copayment of €100, 47% of the SRPs would choose to visit their GP instead of the ED. There was no specific copayment level that resulted in reducing mainly inappropriate ED visits.
Zika virus and diagnostics
Authors: Gabaglia Claudia Raja 
Published: November 2016

Purpose of review
The purpose of this review is to present what is known about the Zika virus (ZIKV) at the time of writing this review. The viral structure and its phylogeny, as well as the limitations of current available techniques used for diagnosis, are discussed.

Recent findings
Crystallography and cryo-electron microscopy of the whole ZIKV, or a few of its proteins, are confirming its overall antigenic relatedness to other flaviviruses. Sequencing has revealed its dynamic genetic variation and has placed the Western cluster of Zika isolates within the Asian phylogenic tree. Genetic codon mutations, although highly prevalent, do not usually translate into modifications at amino acid or proteomic levels, revealing conserved enzymatic functions that could potentially be addressed therapeutically. Clinical characterization of ZIKV infection is complicated because of symptoms similar to dengue and chikungunya. Diagnosis requires specialized laboratories with costly reagents and highly trained personnel. Although commercial labs are now offering ZIKV diagnostic tests, most of them are not fully tested in comparison with standard molecular techniques standardized at CDC and local health departments. We are still in desperate need of simpler diagnostic tests that better discriminate ZIKV from coendemic arboviruses.

Summary
The area of better Zika diagnostic assays is a rapidly developing field with the public attention directed to this epidemic. Academic interest in this topic is driving fast disclosure of information in peer-reviewed journals and grey papers via web-based forums. We expect in the near future that new promising strategies for improved Zika diagnostics will translate into preventive and therapeutic tools.
Validation of a Simple Stool Diary Used by Caregivers to Document Diarrhea Among Young Children in a Low‐Income Country
Authors: Grenov Benedikte , Namusoke Hanifa , Nabukeera‐Barungi Nicolette , Lanyero Betty , Ritz Christian , Carlsson Amalie , Vinther Cecilie K. , Michaelsen Kim F. , Holm‐Larsen Tove 
Published: November 2016

ABSTRACTObjectives:The aim of the study was the development and validation of a simple stool diary for caretakers collecting data on stool frequency and consistency among young children in a low‐income country.Methods:Focus group studies evaluated how diarrhea was understood by caregivers (content validity). The sensitivity, reliability, and correlations between dehydration and diary scores (construct validity) were tested in a clinical trial.Results:Caregivers recognized and understood the concept and severity of diarrhea. Stool frequency and liquid consistency decreased in children admitted with diarrhea (P < 0.0001 for both), confirming good sensitivity of the diary. High reliability was obtained after a few days of training. The caregiver intracorrelation coefficients were 0.66 (0.55–0.77) and 0.75 (0.66–0.84) after 2 and 7 days of training, respectively, and subjective staff evaluation of caregiver scores showed that ⩽6% of caregivers had low scoring abilities after 3 days. The degree of dehydration (4‐point score) was correlated with both increasing stool frequency and liquid stool consistency (+0.2 points [0.07–0.3], P = 0.0018 for 6 or more diarrheal stools, compared to 3 or more diarrheal stools per day, and +0.5 points (0.3–0.6), P < 0.0001 for diarrheal episodes with 3 or more watery stools/day compared with episodes with 3 or more “watery + abnormally loose + loose” stools per day).Conclusions:The diary showed high validity, good reliability, and high sensitivity. After 3 days of training, caregivers with mainly no or limited education could report stool consistency with good reliability. Stool consistency, which correlated strongly with dehydration, may be considered an important marker of diarrhea severity in future research.
Tumor Necrosis Factor‐Alpha Inhibitor Etanercept Does Not Alter Methotrexate‐Induced Gastrointestinal Mucositis in Rats
Authors: Kuiken Nicoline S.S. , Rings Edmond H.H.M. , Alffenaar Jan‐Willem C. , Havinga Rick , Jurdzinski Angelika , Groen Albert K. , Tissing Wim J.E. 
Published: November 2016

ABSTRACTObjectives:Gastrointestinal (GI) mucositis is a severe adverse effect of chemotherapy and radiotherapy. Proinflammatory cytokines are thought to play an important role in the pathophysiology of GI mucositis. We aimed to determine the effect of the tumor necrosis factor‐alpha (TNF‐α) inhibitor etanercept on the severity of mucositis in a previously established methotrexate (MTX)‐induced GI mucositis rat model.Methods:Male Wistar rats received 60 mg/kg MTX on day 0 intravenously. Rats were treated daily with either etanercept (TNF‐α inhibitor) 5 mg/kg or NaCl 0.9% subcutaneously from day −3 till day 3. Control rats received NaCl 0.9% intravenously and etanercept subcutaneously. The severity of mucositis was determined by intake, bodyweight, plasma citrulline, and by a function test (absorption of an oral glucose bolus). On day 4 and day 10 rats were terminated. Villus length, crypt length, intestinal myeloperoxidase, and plasma etanercept levels were determined.Results:The administration of MTX induced mucositis in all rats. Etanercept did not cause a change in the degree of mucositis. Bodyweight, intake, and glucose levels were not altered by etanercept; villus length was comparable; and there was no difference in myeloperoxidase and citrulline level. Etanercept levels in plasma were significantly increased in the etanercept rats (P < 0.05).Conclusions:TNF‐α inhibitor etanercept did not alter the severity of mucositis in the rat, suggesting that targeting only the inflammatory pathway of TNF‐α is not effective for decreasing the severity of GI mucositis induced by high‐dose MTX. Etanercept alone is not useful for the treatment of MTX‐induced GI mucositis.