bluuebunny/crossref_metadata_2025 huggingface dataset:
Three‐dimensional Printing in Anatomy Education: Assessing Potential Ethical Dimensions
Authors: Jones David Gareth
Published: December 2018

New technological developments have frequently had major consequences for anatomy education, and have raised ethical queries for anatomy educators. The advent of three‐dimensional (3D) printing of human material is showing considerable promise as an educational tool that fits alongside cadaveric dissection, plastination, computer simulation, and anatomical models and images. At first glance its ethical implications appear minimal, and yet the more extensive ethical implications around clinical bioprinting suggest that a cautious approach to 3D printing in the dissecting room is in order. Following an overview of early groundbreaking studies into 3D printing of prosections, organs, and archived fetal material, it has become clear that their origin, using donated bodies or 3D files available on the Internet, has ethical overtones. The dynamic presented by digital technology raises questions about the nature of the consent provided by the body donor, reasons for 3D printing, the extent to which it will be commercialized, and its comparative advantages over other available teaching resources. In exploring questions like these, the place of 3D printing within a hierarchical sequence of value is outlined. Discussion centers on the significance of local usage of prints, the challenges created by regarding 3D prints as disposable property, the importance of retaining the human side to anatomy, and the unacceptability of obtaining 3D‐printed material from unclaimed bodies. It is concluded that the scientific tenor of 3D processes represents a move away from the human person, so that efforts are required to prevent them accentuating depersonalization and commodification.
From Endogenous Compounds as Biomarkers to Plasma‐Derived Nanovesicles as Liquid Biopsy; Has the Golden Age of Translational Pharmacokinetics‐Absorption, Distribution, Metabolism, Excretion‐Drug–Drug Interaction Science Finally Arrived?
Authors: Rodrigues David , Rowland Andrew
Published: December 2018

It is now established that a drug's pharmacokinetics (PK) absorption, distribution, metabolism, excretion (ADME) and drug–drug interaction (DDI) profile can be modulated by age, disease, and genotype. In order to facilitate subject phenotyping and clinical DDI assessment, therefore, various endogenous compounds (in plasma and urine) have been pursued as drug‐metabolizing enzyme and transporter biomarkers. Compared with biomarkers, however, the topic of circulating extracellular vesicles as “liquid biopsy” has received little attention within the ADME community; most organs secrete nanovesicles (e.g., exosomes) into the blood that contain luminal “cargo” derived from the originating organ (proteins, messenger RNA, and microRNA). As such, ADME profiling of plasma exosomes could be leveraged to better define genotype‐phenotype relationships and the study of ontogeny, disease, and complex DDIs. If methods to support the isolation of tissue‐derived plasma exosomes are successfully developed and validated, it is envisioned that they will be used jointly with genotyping, biomarkers, and modeling tools to greatly progress translational PK‐ADME‐DDI science.
Estimating range expansion of wildlife in heterogeneous landscapes: A spatially explicit state‐space matrix model coupled with an improved numerical integration technique
Authors: Osada Yutaka , Kuriyama Takeo , Asada Masahiko , Yokomizo Hiroyuki , Miyashita Tadashi
Published: December 2018

Dispersal as well as population growth is a key demographic process that determines population dynamics. However, determining the effects of environmental covariates on dispersal from spatial‐temporal abundance proxy data is challenging owing to the complexity of model specification for directional dispersal permeability and the extremely high computational loads for numerical integration. In this paper, we present a case study estimating how environmental covariates affect the dispersal of Japanese sika deer by developing a spatially explicit state‐space matrix model coupled with an improved numerical integration technique (Markov chain Monte Carlo with particle filters). In particular, we explored the environmental drivers of inhomogeneous range expansion, characteristic of animals with short dispersal. Our model framework successfully reproduced the complex population dynamics of sika deer, including rapid changes in densely populated areas and distribution fronts within a decade. Furthermore, our results revealed that the inhomogeneous range expansion of sika deer seemed to be primarily caused by the dispersal process (i.e., movement barriers in fragmented forests) rather than population growth. Our state‐space matrix model enables the inference of population dynamics for a broad range of organisms, even those with low dispersal ability, in heterogeneous landscapes, and could address many pressing issues in conservation biology and ecosystem management.
In vitro protein tyrosine phosphatase 1B inhibition and antioxidant property of different onion peel cultivars: A comparative study
Authors: Yang Su Jin , Paudel Pradeep , Shrestha Srijan , Seong Su Hui , Jung Hyun Ah , Choi Jae Sue
Published: December 2018

The aim of the present study was a comparative investigation of water and 70% ethanol extracts derived from yellow and red onion (Allium cepa L.) peels against diabetes and diabetic complications. The total phenolic contents (TPCs) and total flavonoid contents (TFCs) of each cultivar, measured to assess phytochemical characteristics, showed a direct correlation with the in vitro antioxidant effects. Among the two captives, the yellow onion peel extract showed higher antioxidant activity than red one. However, all extracts exhibited significant protein tyrosine phosphatase 1B (PTP1B) inhibitory activity (IC50; 0.30–0.86 μg/ml), showing water extracts more potent (IC50; approximately 0.3 μg/mL), than the 70% ethanol extracts (IC50; approximately 0.8 μg/ml). Similarly, in insulin‐resistant HepG2 cells, all extracts enhanced the glucose uptake and reduced the expression of PTP1B in a concentration‐dependent manner, water extract displaying better activity. Our results overall suggest that in vitro antioxidant and antidiabetic potentials vary among red and yellow cultivars and extracting solvents, which could therefore be a promising strategy to prevent diabetes and associated complications.
Agrarian landscapes in the Iberian Iron Age: Mountain communities and land use in southeastern Iberia
Authors: González Reyero Susana , Sánchez‐Palencia Francisco Javier , López‐Sáez José Antonio , Pérez‐Díaz Sebastián , Ruiz‐Alonso Mónica , Romero Perona Damián , Vallés Iriso Javier , Álvarez‐Ayuso Esther
Published: December 2018

Agrarian landscapes are among the least understood features of first millennium B.C. societies in the western Mediterranean. Studies of such landscapes in the context of the Iberian Iron Age have been based essentially on the archeological record in places used for purposes other than farming, particularly settlements and areas reserved for burials and rituals, or on the identification of the possible use of fertilizers. Here we present a multiproxy analysis of an agrarian landscape based on geoarchaeological and paleoenvironmental studies in a mountainous region in southeastern Iberia. The findings confirmed the existence of farmland cultivated as early as the first millennium B.C. in the high Jutia Valley in the Spanish province of Albacete. These results suggest that coordinated analyses can be highly useful for identifying enduring agricultural practices, while contributing to a fuller understanding of western Mediterranean agrarian landscapes and their millenarian resilience, attributable to the coevolution of human communities and the environment.
A multianalytical approach for identifying a manganese source for the black pigment of the Chinchorro mortuary palette
Authors: Van Hoesen John , Arriaza Bernardo , Ryan Peter , Grady C.
Published: December 2018

The primary goal of this study was to characterize and evaluate the potential origins of manganese‐based paint used to decorate the Chinchorro mummies of northern Chile. We sampled small painted fragments from the trunk of two black mummies and nine samples from the cranium/face of the red mummies. In addition, we sampled manganese‐bearing rocks from the Lauca and Huaylas Formations exposed in the Altiplano, approximately 80–90 km northeast of Arica, Chile. Using scanning electron microscopy, energy‐dispersive spectroscopy, X‐ray diffraction, inductively coupled plasma mass spectrometry, and oxygen isotopic data, we propose these two formations are the likely source of manganese used by the Chinchorro culture to create their distinctive mortuary paint. However, the processes by which they collected and transported the raw material are still unclear. It is possible that Chinchorro traveled to the Altiplano, but a more likely cost‐benefit scenario is that manganese‐rich clasts were transported to lower elevations via rivers fed by seasonal rain and snowmelt.
Erosion of archaeological sites: Quantifying the threat using optically stimulated luminescence and fallout isotopes
Authors: Huisman Hans , de Kort Jan‐Willem , Ketterer Michael E. , Reimann Tony , Schoorl Jeroen M. , van der Heiden Menno , van Soest Maud , van Egmond Fenny
Published: December 2018

Although visible evidence shows that erosion has damaged many archaeological sites, especially when tilled, there has hitherto been scant attention to its quantitative assessment. Accordingly, the archaeology communities lack insight into whether long‐term threats to the stability and integrity of soils at these sites allow these cultural repositories to be preserved for future human generations. Of the techniques that are available to measure erosion rates, few have been tested on the timescales needed. We selected three archaeological sites with high expected erosion rates. We combined optically stimulated luminescence (OSL) dating with analyses of radioactive fallout isotope distributions to assess erosion patterns and rates. An age–depth representation of OSL single‐aliquot results was developed to determine past erosion, and to identify stable land surfaces on centennial to millennia timescales. Fall‐out isotopes of cesium (Cs) and plutonium (Pu) were suitable for shorter timescales: The 240Pu/239Pu ratios and a correlation between activities of 239+240Pu and 137Cs demonstrated the weapons testing fallout origin of these isotopes in the ~1952–1966 timeframe. Erosion rates in recent decades ranged from 2 to 6 mm/year on the studied sites. Our results indicate that erosion is not only tied to the past, but keeps on threatening archaeological sites.
Blind test evaluation of consistency in macroscopic lithic raw material sorting
Authors: Agam Aviad , Wilson Lucy
Published: December 2018

Most archaeological lithic raw material studies depend upon a macroscopic classification. However, since the human eye is a limited tool, some inconsistencies in classification may arise. Thus, a process for evaluating and increasing the reliability of macroscopic classification is needed. We present the results of a blind test designed to evaluate consistency in macroscopic lithic materials analysis, based on archaeological material taken from the Acheulo‐Yabrudian site Qesem Cave (Israel), focusing on interobserver error, aimed at identifying consistencies and weaknesses within our own study scheme. Twelve students, with various degrees of experience and familiarity with the Qesem material, sorted 100 randomly selected flint pieces into flint types, based on a previously established database, after a brief tutorial process. In addition, the authors, LW and AA, performed the same test. We then compared the results, using LW's results as an anchor. Our results show that experience affects the consistency in classification, demonstrating that it is an acquired skill. Furthermore, the blind test allowed us to identify weaknesses within the classification scheme. We suggest that blind tests should be regularly used to check accuracy and reproducibility of results and to assess the definitions set by the analyst, allowing fine‐tuning and calibration of the classification process.
Origin site‐based staging system of sinonasal inverted papilloma for application to endoscopic sinus surgery
Authors: Meng Yifan , Fang Gaoli , Wang Xiangdong , Song Xiaohong , Wang Kuiji , Lou Hongfei , She Wenyu , Qin Long , Lv Mei , Zhang Tao , Yuan Tiejun , Tao Yanli , Meng Xun , Zhang Luo , Wang Chengshuo
Published: December 2018

Background

We aimed to assess the recurrence risk of sinonasal inverted papillomas (SNIPs), based on a staging system developed according to the originating site of SNIP.

Methods

A total of 200 patients with SNIP were enrolled, and a staging system was developed based on the originating sites and corresponding recurrence rates of tumor in the patients. In the verification phase, 675 patients with SNIPs were enrolled as above, and the originating sites of the SNIPs were confirmed by an endoscopic sinus surgery. Cluster analysis was performed to determine the stage for each SNIP.

Results

Overall, 608 patients completed the study. SNIP recurrence rates for stages 1‐4 were 0 (n = 43), 4.0% (n = 420), 13.4% (n = 134), 36.4% (n = 11), respectively (total = 6.4%).

Conclusions

The origin site‐based classification of SNIP may aid surgeons in selecting appropriate endoscopic surgical approaches to minimize the risk of recurrence.
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

Background

Gnathodiaphyseal dysplasia (GDD) is a rare skeletal disorder that has not been well studied.

Methods

Sanger sequencing, whole‐genome sequencing (WGS), and bioinformatics and structural modeling analyses were performed.

Results

A 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.

Conclusions

The 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

Background

Epithelial–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).

Methods

Using 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.

Results

CD44 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).

Conclusions

CD44 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

Background

We 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.

Methods

A 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.

Results

In 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.

Conclusions

Post‐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

Background

Recommendations 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.

Methods

Patients 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.

Results

Samples 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.

Conclusion

Circulating 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

Currently, 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

A 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

Background

The 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.

Aim

The 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.

Method

The 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.

Results

Nine 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.

Conclusion

Most 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

Background

Oral anticancer medication (OAM) use is increasing in prevalence. Although OAM offers many advantages to patients, there is also a high risk of medication errors.

Aim

This study aimed to evaluate whether a pharmacist‐led OAM management clinic would improve patient understanding and adherence to OAMs and reduce medication errors.

Methods

Patients 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.

Results

In 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.

Conclusion

Although 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

Background

Therapeutic 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.

Aim

The aim of this study was to evaluate the therapeutic drug monitoring (TDM) of high‐risk drugs, using Bayesian simulation.

Methods

Patients 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.

Results

In 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.

Conclusion

Bayesian 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

Background

Inappropriate 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.

Aim

The aim of this study was to determine the incidence, pattern, predictors and cost implications of inappropriate prescribing of antimalarials among elderly in‐patients.

Methods

A 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.

Results

During 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).

Conclusion

Strict 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

Background

Medication safety officers are the cornerstone of a successful medication safety culture. Their main responsibility is reporting and preventing medication errors (MEs).

Aim

The 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.

Methods

The present study was a prospective evaluation with descriptive analysis performed in three hospitals with different specialities (internal medicine, paediatrics and cardiology) in Saudi Arabia.

Results

From 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.

Conclusions

Medication 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

Developments 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 Objectives

The 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.

Methods

Patients 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.

Results

The 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).

Conclusion

iCRS 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.
Re‐examining the role of adjuvant radiation therapy
Authors: Spillane Andrew , Hong Angela , Fogarty Gerald
Published: December 2018

Previously important roles for adjuvant radiotherapy (RT) in melanoma patients included improved regional control after resection of high‐risk nodal disease, to reduce local recurrence for desmoplastic, and other subtypes of melanoma with neurotropism, reducing in‐brain relapse of brain metastases after surgery and other situations on a case‐by‐case basis. This review evaluates the integration of adjuvant RT into clinical practice at this time of rapidly evolving knowledge and improving outcomes from effective systemic therapy.
Management and outcomes among patients with mixed hepatocholangiocellular carcinoma: A population‐based analysis
Authors: Spolverato Gaya , Bagante Fabio , Tsilimigras Diamantis , Ejaz Aslam , Cloyd Jordan , Pawlik Timothy M.
Published: December 2018

Background

We sought to define the management of mixed hepatocellular carcinoma‐intrahepatic cholangiocarcinoma (HCC‐ICC) as well as characterize short‐ and long‐term outcomes of patients with mixed HCC‐ICC.

Methods

Patients diagnosed with HCC‐ICC, HCC, or ICC between 2004 and 2015 were identified from the National Cancer Data Base using the International Classification of Diseases for Oncology codes. Short‐ and long‐term outcomes were assessed using univariate and multivariate analyses.

Results

Among 174 454 patients, 86.8% had HCC, 12.1% ICC, and 1.1% HCC‐ICC. The incidence of lymphadenectomy was 55.6% among ICC patients vs 15.1% and 34.2% for HCC and HCC‐ICC patients, respectively (P < 0.001). A 90‐day mortality was comparable among patients with HCC (9.1%), ICC (8.8%), and HCC‐ICC (10.5%) (all P > 0.2). While 42.0% of ICC patients received adjuvant chemotherapy, adjuvant chemotherapy among HCC and HCC‐ICC patients was 13.1% and 27.4%, respectively (P < 0.001). A 5‐year survival was 43.5% (95% CI, 42.5‐44.5), 33.3% (95% CI, 31.4‐35.3), 34.4% (95% CI, 29.1‐39.8) for HCC, ICC, and HCC‐ICC patients, respectively.

Conclusion

Patients who underwent resection of mixed HCC‐ICC had a prognosis that was comparable to ICC, yet worse than HCC. Utilization of lymphadenectomy and adjuvant therapy were low. HCC‐ICC remains a rare disease with a guarded prognosis that should be treated in a multidisciplinary setting.
Is malnutrition associated with postoperative complications in patients with primary bone sarcomas?
Authors: Park Andrew , Lans Jonathan , Raskin Kevin , Hornicek Francis , Schwab Joseph , Lozano Calderon Santiago
Published: December 2018

Background

Modifiable risk factors that can be optimized to minimize postoperative complications in patients with bone sarcomas are yet to be identified.

Methods

We retrospectively identified 275 patients aged 18 and older who underwent surgery for primary bone sarcomas who also had albumin values recorded within 4 weeks before surgery. Postoperative complications were defined as infection, hematoma, need for additional surgery, or wound complications.

Results

In the multivariate analysis, age (P = 0.049) and neoadjuvant radiotherapy (P = 0.008) were independently associated with postoperative complications. We then performed a subanalysis of patients without a pelvic tumor who also did not receive radiotherapy (n = 178). In this population, albumin less than 2.8 g/dL was found to be independently associated with postoperative complications (odds ratio [OR], 4.69. 95% confidence intervals [CI], 1.03‐21.97; P = 0.046).

Conclusions

This study demonstrates that hypoalbuminemia (albumin < 2.8 g/dL) is associated with postoperative complications in patients with nonpelvic bone sarcomas who do not receive radiation. Future studies are necessary to further elucidate the role of nutrition, and they may show that nutritional status is a modifiable risk factor that can be optimized to improve the outcome of surgery for primary bone sarcomas.
Deficiencies in postoperative surveillance for veterans with gastrointestinal cancer
Authors: Taylor Lauren J. , Xu Kerui , Maloney James D. , Voils Corrine I. , Weber Sharon M. , Funk Luke M. , Abbott Daniel E.
Published: December 2018

Background and Objectives

National guidelines for gastrointestinal (GI) cancers offer surveillance algorithms to facilitate detection of recurrent disease, yet adherence rates are unknown. We sought to characterize postoperative surveillance patterns for veterans with GI cancer at a tertiary care Veterans Affairs Hospital.

Methods

A single‐center retrospective cohort study identified patients who underwent surgical resection for colorectal, gastroesophageal or hepatopancreaticobiliary malignancy from 2010‐2016. We calculated the annual rate of cancer‐directed clinic visits and abdominal imaging and used National Comprehensive Cancer Network guidelines as a benchmark by which to assess adequate surveillance.

Results

Ninety‐seven patients met inclusion criteria. Median surveillance time was 1203 days. Overall, 44% of patients had insufficient surveillance. Specifically, 11% received no postoperative imaging and 7% had no cancer‐directed clinic visits. An additional 30% received less than recommended surveillance imaging and 12% attended fewer than recommended clinic visits. By disease site, insufficient imaging was most common for patients with hepatopancreaticobiliary cancer (63%), while inadequate clinic follow‐up was highest for colorectal cancer (24%).

Conclusion

A significant proportion of veterans with GI cancer received either inadequate postoperative surveillance based on national guidelines. This deficiency represents an opportunity for improvement through targeted efforts, including telemedicine and education of patients and providers.
The role of robotic aortic lymphadenectomy in gynecological cancer: surgical and oncological outcome in a single institution experience
Authors: Gallotta Valerio , Federico Alex , Gaballa Khaled , D’Indinosante Marco , Conte Carmine , Giudice Maria Teresa , Naldini Angelica , Lodoli Claudio , Rotolo Stefano , Gallucci Valeria , Tortorella Lucia , Romanò Bruno , Scambia Giovanni , Ferrandina Gabriella
Published: December 2018

Background and Objective

This study aims to investigate the surgical outcomes observed in robotic transperitoneal aortic lymphadenectomy (AL) in gynecological cancer patients.

Methods

Retrospective data were collected and analyzed on 71 patients undergoing robotic surgical procedures for gynecological cancers, including transperitoneal AL, between December 2014 and February 2018 at the Catholic University of the Sacred Heart, Rome, Italy.

Results

Median age of the sample population was 50 years (range, 26‐76 years). The median operative time was 210 minutes (range, 75‐480 minutes), the median estimated blood loss was 50 ml (range, 20‐300 ml). The number of para‐aortic nodes removed was 12 (range, 7‐43). In the whole series, 13 patients (18.3%) had at least one metastatic node. Overall, 10 patients (14.1%) experienced any grade early postoperative complications. Three patients experienced more than one complication. Three intraoperative complications occurred with two cases of vascular injury. Conversion to laparotomy was necessary for one patient (1.4%).

Conclusions

The present study shows the safety and adequacy of robotic transperitoneal AL as surgical staging step for gynecological cancers in terms of perioperative and postoperative outcomes.
Completion surgery of residual disease after primary inadequate surgery of retroperitoneal sarcomas can salvage a selected subgroup of patients—A propensity score analysis
Authors: Nizri Eran , Fiore Marco , Colombo Chiara , Radaelli Stefano , Callegaro Dario , Sanfilippo Roberta , Sangalli Claudia , Collini Paola , Morosi Carlo , Stacchiotti Silvia , Casali Paolo G. , Gronchi Alessandro
Published: December 2018

Background

Patients with retroperitoneal sarcoma (RPSs) who undergo primary inadequate surgery before referral to specialized sarcoma centers may be considered for completion surgery (CS). We wanted to compare the outcome of these patients to those who underwent primary adequate surgery (PAS) at a single referral institution.

Methods

We identified 34 patients who were referred for CS after primary inadequate surgery. Using a propensity score based on validated RPS outcome risk factors, we managed to match 28 patients to patients with PAS.

Results

Median time lag between the first and second operation in CS patients was 5 months (2‐15). Surgical extent was similar among groups (median number of organs resected = 3; P = 0.08), and macroscopically complete excision was achieved in all patients. The rate of severe complications did not differ between the groups (1 of 28 vs 3 of 28, respectively; P = 0.35) and no perioperative mortality was documented. Median follow‐up was 43.5 months. Patients in the CS group had similar local recurrence‐free survival (mean, 92.1 ± 9.7 vs 99.8 ± 12.4; P = 0.85) and relapse‐free survival (mean, 88.7 ± 9.8 vs 80.9 ± 12.3; P = 0.3) to those with PAS.

Conclusions

CS has short‐ and long‐term outcomes comparable to PAS. While primary surgery should always be carried out at a referral institution, some of the patients who undergo an initial incomplete resection at a non specialist center can still be offered a salvage procedure at a referral institution with comparable results.
Structural Validity of the World Assumption Scale
Authors: van Bruggen Vincent , ten Klooster Peter M. , van der Aa Niels , Smith Annemarie J.M. , Westerhof Gerben J. , Glas Gerrit
Published: December 2018

The World Assumption Scale (WAS) is a frequently used measure in trauma research. The 32 items of the WAS are intended to represent eight assumptions about the benevolence of the world, the meaningfulness of events, and the worthiness of the self. Debate about the validity of the WAS is ongoing, particularly in terms of its empirical factor structure; some studies have confirmed a model of eight correlated factors whereas several other studies have not. The WAS items were administered to a clinical sample of patients who sought professional help because of posttraumatic complaints (n = 1,791) as well as a sample of healthcare professionals (n = 236). We split the clinical sample into three subsamples, then performed exploratory factor analysis using data from one subsample and tested the factor structure with confirmatory factor analysis using the other two subsamples. A consistent model of eight correlated factors was demonstrated, with almost all factors showing acceptable reliability, Cronbach's αs = .68–.84. We tested this factor model against data from the sample of healthcare professionals with increasingly stringent levels of invariance and found it to be scalar invariant (same structure, loadings, and thresholds). In a regression analysis, five factors showed significant associations with posttraumatic stress disorder (PTSD) symptoms, and two factors had unique associations with PTSD symptoms after we controlled for traumatic events: Self‐Worth, β = −.31; and Luck, β = −.15. Future research should aim to distinguish between different assumptions and their individual influences on posttraumatic complaints.