bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel ANO5 mutation c.1067G>T (p.C356F) identified by whole genome sequencing in a big family with atypical gnathodiaphyseal dysplasia
Authors: Zeng Binghui , Liao Junkun , Zhang Hanqing , Fu Sha , Chen Weixiong , Pan Guokai , Li Qunxing , Chen Weiliang , Ferrone Soldano , Wu Binghao , Sun Sheng , Hu Jiali , Ahn Michael Ho‐Young , Lin Zhaoyu , Yu Dongsheng , Ou Zhanpeng , Wang Xinhui , Mo Fengbo , Huang Nasi , Hamilton James A. , Li Jinsong , Fan Song 
Published: December 2018

AbstractBackgroundGnathodiaphyseal dysplasia (GDD) is a rare skeletal disorder that has not been well studied.MethodsSanger sequencing, whole‐genome sequencing (WGS), and bioinformatics and structural modeling analyses were performed.ResultsA family with patients with fibro‐osseous lesions of the jawbones were initially diagnosed with cherubism. Sequencing of SH3BP2, which is the causal gene of cherubism, revealed no pathogenic mutation. Through WGS, we identified a novel mutation c.1067G>T (p.C356F) in ANO5, and bioinformatics analyses and structural modeling showed that the mutation was deleterious. Because ANO5 is the gene responsible for GDD, we reappraised the clinical data of the patients, and the diagnosis was corrected to atypical GDD. A review of the literature showed that 67% of GDD cases confirmed by molecular testing were initially misdiagnosed.ConclusionsThe novel mutation c.1067G>T (p.C356F) in ANO5 is responsible for the atypical GDD observed in our patients. GDD should be included in the differential diagnosis for patients with fibro‐osseous lesions.
Preoperative assessment of CD44‐mediated depth of invasion as predictor of occult metastases in early oral squamous cell carcinoma
Authors: Morand Grégoire B. , Ikenberg Kristian , Vital Domenic G. , Cardona Isabel , Moch Holger , Stoeckli Sandro J. , Huber Gerhard F. 
Published: December 2018

AbstractBackgroundEpithelial–mesenchymal transition and cancer stem‐like cells (CSC) have been linked to increased metastatic potential. We evaluated the prognostic impact of CD44, a CSC biomarker, on depth of invasion (DOI) and outcome in oral squamous cell carcinoma (OSCC).MethodsUsing a multivariable logistic regression model, we evaluated in early OSCCs the relationship between CD44 expression at the invasive tumor front, DOI, sentinel lymph node biopsy, extension of nodal involvement, and survival. We also assessed whether CT and/or MRI could predict DOI preoperatively.ResultsCD44 expression was associated with increased DOI (P = .018), worse disease‐specific survival (P = .041) but not with positive sentinel lymph node biopsy (P > .05). Each millimeter increase in DOI was associated with a 31.1% higher risk for positive sentinel lymph node biopsy (95% CI: 5.8%‐62.4%, P = .013) and with higher metastatic ratio (P = .015). Preoperative estimation of DOI by CT and/or MRI and histopathological DOI showed a strong correlation (P < .0001).ConclusionsCD44 expression correlates with DOI, which predicts occult lymph node metastasis. Preoperative CT and/or MRI provides an accurate estimation of histopathological DOI. Both pieces of information gained preoperatively can help surgeons tailor their operation in regard to the surgical management of the neck.
Shoulder symptoms and quality of life impact of limited neck dissection after de‐intensified chemoradiotherapy: Secondary analysis of two prospective trials
Authors: Wang Kyle , Moon Dominic H. , Amdur Robert J. , Dagan Roi , Sheets Nathan C. , Shen Colette J. , Green Rebecca , Patel Samip N. , Zanation Adam M. , Thorp Brian D. , Hackman Trevor G. , Weissler Mark C. , Mendenhall William M. , Chera Bhishamjit S. 
Published: December 2018

AbstractBackgroundWe investigated the quality of life (QOL) impact of post‐radiation therapy (RT) superselective/selective neck dissection after de‐intensified chemoradiation for human papillomavirus‐associated oropharynx cancer.MethodsA total of 147 patients received 60 Gy and weekly low‐dose cisplatin on two phase 2 trials with planned post‐RT neck dissection or surveillance positron emission tomography with neck dissection reserved for salvage. UW‐QOL Shoulder Score, EORTC H&N‐35, and EAT‐10 were assessed.ResultsIn all, 48 of 147 patients had post‐RT neck dissection. At 2 years, 37% and 13% of patients receiving post‐RT neck dissection had Shoulder Score ≥ 1 (any shoulder symptoms) and ≥ 2 (symptoms affecting work/hobbies), respectively, versus only 16% and 3% of patients not receiving post‐RT neck dissection. Post‐RT neck dissection was associated with Shoulder Score ≥ 1 (P = 0.005) and Shoulder Score ≥ 2 (P = 0.03) at 2 years, but not H&N‐35 or EAT‐10 scores.ConclusionsPost‐RT superselective/selective neck dissection was associated with modest but persistent shoulder symptoms. These toxicities should be weighed against the probability of persistent disease when evaluating patients for post‐RT neck dissection.
Plasma circulating tumor DNA as a potential tool for disease monitoring in head and neck cancer
Authors: Egyud Matthew , Sridhar Praveen , Devaiah Anand , Yamada Emiko , Saunders Stefanie , Ståhlberg Anders , Filges Stefan , Krzyzanowski Paul M. , Kalatskaya Irina , Jiao Wei , Stein Lincoln D. , Jalisi Scharukh , Godfrey Tony E. 
Published: December 2018

AbstractBackgroundRecommendations for perioperative therapy in head and neck cancer are not explicit and recurrence occurs frequently. Circulating tumor DNA is an emerging cancer biomarker, but has not been extensively explored for detection of recurrence in head and neck cancer.MethodsPatients diagnosed with head and neck squamous cell carcinoma were recruited into the study protocol. Tumors were sequenced to identify patient‐specific mutations. Mutations were then identified in plasma circulating tumor DNA from pre‐treatment blood samples and longitudinally during standard follow‐up. Circulating tumor DNA status during follow‐up was correlated to disease recurrence.ResultsSamples were taken from eight patients. Tumor mutations were verified in seven patients. Baseline circulating tumor DNA was positive in six patients. Recurrence occurred in four patients, two of whom had detectable circulating tumor DNA prior to recurrence.ConclusionCirculating tumor DNA is a potential tool for disease and recurrence monitoring following curative therapy in head and neck cancer, allowing for better prognostication, and/or modification of treatment strategies.
Quantitative analysis and evaluation of manipulation comfort of tractor gear shifting based on combined methods
Authors: Xu Hongmei , Zhong Wenjie , Wang Chenglong , Liu Shuang , Liu Haiyue , Jiang Wei , Dong Jiajun 
Published: December 2018

AbstractCurrently, studies of the manipulation comfort of agriculturalmachinery are mainly based on qualitative analysis and subjective evaluation. This study is mainly focused on the quantitative analysis and evaluation of the manipulation comfort of tractor gear‐shifting. By taking various factors into account, a combined evaluation model and the corresponding indicator system were proposed based on the method of maximizing deviations. The data of pedal force and stroke length of the clutch were collected from eight different types of agricultural tractors, which were used as the basic data for subsequent analyses. Then, five evaluation methods, including principal component analysis (PCA), comprehensive evaluation based on the entropy, ideal solution (TOPSIS), improved TOPSIS and grey correlation analysis, were adopted to evaluate the manipulation comfort of tractor gear‐shifting. A consistency check on the evaluation results of the five methods was conducted by using the concordance coefficient method of KENDALL. Furthermore, the combined weight vector of the compatible method set was calculated by maximizing the deviations. Through comparison, we found that the evaluation results of the combined methods were consistent with the subjective evaluation results. The method of combined evaluation can compensate for the insufficiency of single methods and overcome the inconsistency of the evaluation, and thus can produce more objective and accurate results. Our results can provide references for the quantitative research of manipulation comfort of agricultural machinery equipment.
Linking systems of difference sets
Authors: Jedwab Jonathan , Li Shuxing , Simon Samuel 
Published: December 2018

AbstractA linking system of difference sets is a collection of mutually related group difference sets, whose advantageous properties have been used to extend classical constructions of systems of linked symmetric designs. The central problems are to determine which groups contain a linking system of difference sets, and how large such a system can be. All previous constructive results for linking systems of difference sets are restricted to 2‐groups. We use an elementary projection argument to show that neither the McFarland/Dillon nor the Spence construction of difference sets can give rise to a linking system of difference sets in non‐2‐groups. We make a connection to Kerdock and bent sets, which provides large linking systems of difference sets in elementary abelian 2‐groups. We give a new construction for linking systems of difference sets in 2‐groups, taking advantage of a previously unrecognized connection with group difference matrices. This construction simplifies and extends prior results, producing larger linking systems than before in certain 2‐groups, new linking systems in other 2‐groups for which no system was previously known, and the first known examples in nonabelian groups.
Pharmacists’ barriers and attitudes towards research in Kota Kinabalu, Sabah, Malaysia: a qualitative study
Authors: Lee Kristine Sheh Fuen , Tan Sze Ling , Izzati Abdul Halim Zaki , Liau Siow Yen 
Published: December 2018

AbstractBackgroundThe role of pharmacists in the healthcare system has evolved towards facilitating and providing patient‐centred care. Involving pharmacists in research is essential to the advancement of practice; however, at present, the level of involvement of pharmacists in research in Sabah, Malaysia, is low.AimThe aims of this study were to explore the attitudes, perceptions and barriers faced by pharmacists in Sabah and to identify potential strategies to increase the involvement of pharmacists in research.MethodThe present qualitative study comprised a series of in‐depth, face‐to‐face interviews. Pharmacists from public services in Kota Kinabalu, Sabah, were selected using purposive sampling and were interviewed until saturation of themes was reached. All interview sessions were audio recorded and transcribed, with additional notes recorded by a member of the research team. Data were analysed thematically.ResultsNine pharmacists participated in the interviews. Two themes emerged around pharmacists’ attitudes towards research: (1) perspectives regarding willingness; and (2) perceptions of research participation. Some interviewees expressed limited interest in research participation because they underestimated or undervalued the importance of undertaking research. Barriers to research participation were grouped into five themes: perception; communication; resources; skill and knowledge; and recognition and rewards. Strategies such as proper time management and providing adequate staffing in research were suggested to overcome the barriers to participation.ConclusionMost interviewees were not aware of the importance of participating in research in improving health care. Practical strategies were suggested to overcome the barriers to participation, and these strategies should be considered when promoting research participation.
Implementation and evaluation of a pharmacist‐led oral anticancer medication management clinic
Authors: Byrne Aimee E. , Redmayne Grace M. , Lam Thanh , Tran Jenny , Chan Daisy K. 
Published: December 2018

AbstractBackgroundOral anticancer medication (OAM) use is increasing in prevalence. Although OAM offers many advantages to patients, there is also a high risk of medication errors.AimThis study aimed to evaluate whether a pharmacist‐led OAM management clinic would improve patient understanding and adherence to OAMs and reduce medication errors.MethodsPatients commencing OAM in the Oncology Outpatient Clinic between July 2015 and April 2016 were eligible for the study. OAM understanding was evaluated using a patient survey before and after initial pharmacist review, in the middle of the first cycle and prior to the second cycle. Education and symptom management advice were provided, as well as referral if required. Pharmacist interventions were documented, then independently assigned a significance rating by a medical officer and pharmacist. Local community pharmacists were approached to complete a survey investigating their practices and confidence dispensing OAMs.ResultsIn all, 29 patients participated in the clinic. Survey results before and after initial pharmacist review showed a trend towards improved patient understanding, which was maintained mid‐cycle and before the second cycle. In addition, 51 pharmacist interventions were recorded: one of high, 32 of moderate and 18 of minimal clinical significance. Self‐reported adherence mid‐cycle and before the second cycle found that 1/18 and 1/9 patients, respectively, forgot to take a dose of their OAM and that 3/18 and 1/9 patients, respectively, reported not taking a dose for other reasons. The community pharmacist survey revealed that 40 and 50% were confident educating patients about OAM dosage regimens and side effects, respectively.ConclusionAlthough the significance of the pharmacists’ education and interventions cannot be determined because of the small sample size, a valuable service was implemented to meet patient needs and expectations.
Therapeutic drug monitoring: using Bayesian methods to evaluate hospital practice
Authors: Donagher Joni , Barras Michael A. 
Published: December 2018

AbstractBackgroundTherapeutic drug monitoring (TDM) is used to improve effectiveness and reduce toxicity of various high‐risk medications. It is guided by drug specific protocols and/or TDM management software.AimThe aim of this study was to evaluate the therapeutic drug monitoring (TDM) of high‐risk drugs, using Bayesian simulation.MethodsPatients prescribed vancomycin, enoxaparin or warfarin and who had plasma concentrations measured for the purposes of TDM were recruited to the study. A Bayesian software package was used to simulate individual patient concentration time curves incorporating patient demographics, dosing data from their course of therapy and all plasma concentrations. The proportion of therapeutic concentrations was determined using the simulated data for each patient and drug. Combined analysis of all patients allowed identification of gaps in TDM at a hospital level. The appropriateness of sampling time and dose adjustments were also investigated.ResultsIn all, 78 patients were recruited who had 279 observed concentrations to allow simulation. Of the 100 observed vancomycin troughs, 66% were sampled incorrectly, as were 34% of 32 observed peak anti‐Xa concentrations (measurement of activity for enoxaparin); all international normalised ratios (INRs) were taken appropriately. Approximately 50% of simulated concentrations were not therapeutic. Most patients administered vancomycin had subtherapeutic concentrations for the first 24–48 h of therapy and most patients treated with enoxaparin had toxic anti‐Xa concentrations within the first 96 h of therapy. INRs were therapeutic only 68% of the time.ConclusionBayesian simulation allowed the identification of gaps in the TDM service and future dose recommendations, including the use of loading doses for vancomycin and dose reductions in extended courses of enoxaparin. TDM practices can now be optimised with the aim of incorporating Bayesian software into clinical practice.
Inappropriate prescribing of antimalarial therapy for the treatment of undifferentiated febrile illness among the elderly
Authors: Menon Vineetha Bharathan , Ramesh Madhan , Pereira Pratibha , Chilkunda Raviprakash Venkatesh , Undela Krishna 
Published: December 2018

AbstractBackgroundInappropriate prescribing results in serious health outcomes in the elderly, increasing morbidity and mortality and wasting resources. In developing countries, physicians sometimes ignore parasitological diagnoses and presumptively treat fever as malaria, leading to overtreatment and drug resistance.AimThe aim of this study was to determine the incidence, pattern, predictors and cost implications of inappropriate prescribing of antimalarials among elderly in‐patients.MethodsA prospective interventional study was performed over 18 months at the Department of Internal Medicine, in a tertiary care teaching hospital. Fever case management of all patients was studied to identify inappropriate antimalarial prescriptions without a confirmed diagnosis. Root cause analysis was performed to characterise inappropriate prescribing, along with economic implications.ResultsDuring the study period, 403 fever cases were reported, of which 36% (n = 145) received a malaria test. Although 94% (n = 137) tests returned negative results, 32% (n = 44) of these patients were prescribed antimalarial drugs without a confirmed diagnosis, primarily monotherapy with injectable artesunate (61%) for an average of 4 days, resulting in 41% overdoses and 38% underdoses. The estimated direct cost associated with inappropriate prescribing wasUS$1291.67. Female bedridden patients who presented with fever associated with chills and rigors and hospitalised for longer were more likely to be irrationally prescribed antimalarials. Except for total leucocyte counts, all the other laboratory examinations were within normal limits for the study cohort (p < 0.05).ConclusionStrict treatment guidelines for antibiotic use and a multidisciplinary team approach are required to prevent inappropriate prescribing and possible adverse effects without affecting health‐related quality of life.
Improving medication safety through implementation of medication error reporting systems in different medical specialities
Authors: Abuelsoud Nermeen Nabeel 
Published: December 2018

AbstractBackgroundMedication safety officers are the cornerstone of a successful medication safety culture. Their main responsibility is reporting and preventing medication errors (MEs).AimThe aims of the present study were to implement a ME reporting system, to determine the effects of this system in different medical specialities and to compare the incidence of MEs detected in these specialities.MethodsThe present study was a prospective evaluation with descriptive analysis performed in three hospitals with different specialities (internal medicine, paediatrics and cardiology) in Saudi Arabia.ResultsFrom January 2013 to December 2015, all MEs that had been detected during clinical rounds were recorded in the ME report form; the treating physician was then notified and the errors were corrected on the basis of the medication safety officer’s recommendations. The ME reporting system detected 3484 MEs. The most frequently detected MEs were drug–drug interactions. The second most frequently identified ME was dosing error, especially in paediatric and cardiology specialities. The recommendations made by the medication safety officer prevented many of the detected MEs from occurring again.ConclusionsMedication safety officers have a vital role in detecting MEs in different specialities. The recommendations of the medication safety officers reported herein succeeded in correcting/preventing many of the errors detected during the study period. In addition, a systematic approach is presented for the implementation of an ME reporting system in different hospitals, as is a comparison of the different types of MEs in different specialities.
Cystic fibrosis: novel therapies, remaining challenges
Authors: Coulthard Kingsley P. 
Published: December 2018

AbstractDevelopments in the treatment of cystic fibrosis (CF) over the past 50 years have seen survival extend from death in the first decade of life to an expected median survival now approaching 50 years of age. Adults with CF now outnumber children, a dramatic shift if one considers that many adult CF clinics were only established in the 1980s. Together with speciality multidisciplinary clinics, new medicines and their aggressive application have played a pivotal role in this achievement. Although there is still no clinically available cure, novel therapies targeting the underlying basic defects have resulted in major beneficial clinical outcomes and quality of life for those living with CF, albeit at significant cost. Although this review concentrates on currently available novel pharmacological therapies, the important role of potential ‘cures’, such as gene therapy, must not be overlooked. The complex drug interactions of the new agents, the need for detailed patient education and research opportunities in CF in general support the role of the specialist pharmacist in CF clinics.
Iterative cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases: A multi‐institutional experience
Authors: Alzahrani Nayef A. , Valle Sarah J. , Fisher Oliver M. , Sugarbaker Paul H. , Yonemura Yutaka , Glehen Olivier , Goere Dianne , Honore Charles , Brigand Cecile , de Hingh Ignace , Verwaal Vic J. , Deraco Marcello , Baratti Dario , Kusamura Shigeki , Pocard Mark , Piso Pompiliu , Maerz Loreen , Marchal Frederic , Moran Brendan , Levine Edward A. , Dumont Frédéric , Pezet Denis , Abboud Karine , Kozman Mathew A. , Liauw Winston , Morris David L. ,   On behalf of the Peritoneal Surface Oncology Group International (PSOGI) and Big‐RENAPE groups
Published: December 2018

Background and ObjectivesThe aims of this multi‐institutional study were to assess the feasibility of iterative cytoreductive surgery (iCRS)/hyperthermic intraperitoneal chemotherapy, iCRS in colorectal peritoneal carcinomatosis (CRPC), evaluate survival, recurrence, morbidity and mortality outcomes, and identify prognostic factors for overall survival.MethodsPatients with CRPC that underwent an iCRS, with or without intraperitoneal chemotherapy, from June 1993 to July 2016 at 13 institutions were retrospectively analyzed from prospectively maintained databases.ResultsThe study comprised of 231 patients, including 126 females (54.5%) with a mean age at iCRS of 51.3 years. The iterative high‐grade (3/4) morbidity and mortality rates were 23.4% and 1.7%, respectively. The median recurrence‐free survival was 15.0 and 10.1 months after initial and iCRS, respectively. The median and 5‐year survivals were 49.1 months and 43% and 26.4 months and 26% from the initial and iCRS, respectively. Independent negative predictors of survival from the initial CRS included peritoneal carcinomatosis index (PCI) > 20 (
P = 0.02) and lymph node positivity (
P = 0.04), and from iCRS, PCI > 10 (
P = 0.03 for PCI 11‐20;
P < 0.001 for PCI > 20), high‐grade complications (
P = 0.012), and incomplete cytoreduction (
P < 0.001).ConclusioniCRS can provide long‐term survival benefits to highly selected colorectal peritoneal carcinomatosis patients with comparable mortality and morbidity rates to the initial CRS procedure. Careful patient selection is necessary to improve overall outcomes.