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A colorimetric polydiacetylene (PDA) paper strip sensor that can specifically recognize Bacillus thuringiensis (BT) HD-73 spores is described in this work. The target-specific aptamer was combined with PDA, and the aptamer-conjugated PDA vesicles were then coated on polyvinylidene fluoride (PVDF) paper strips by a simple solvent evaporation method. The PDA-aptamer paper strips can be used to detect the target without any pre-treatment. Using the paper strip, the presence of BT spores is directly observable by the naked eye based on the unique blue-to-red color transition of the PDA. Quantitative studies using the paper strip were also carried out by analyzing the color transitions of the PDA. The specificity of this PDA sensor was verified with a high concentration of Escherichia coli, and no discernable change was observed. The observable color change in the paper strip occurs in less than 1 h, and the limit of detection is 3 &times, 107 CFU/mL, much below the level harmful to humans. The PDA-based paper sensor, developed in this work, does not require a separate power or detection device, making the sensor strip highly transportable and suitable for spore analysis anytime and anywhere. Moreover, this paper sensor platform is easily fabricated, can be adapted to other targets, is highly portable, and is highly specific for the detection of BT spores.

Vaccination rates of children in the United States remain below the target coverage levels identified in the Healthy People 2020 objectives. Given the success of pharmacists in providing adult vaccinations and the accessibility of pharmacists to the public, expanding pharmacists' authority to vaccinate children may improve vaccination rates of children, particularly in key disease states. This article serves as a Position Statement of the Pediatric Pharmacy Advocacy Group (PPAG), who supports the expansion of pharmacists' authority to vaccinate children. PPAG also believes that increased use of state vaccination registries by pharmacists will help improve communication and documentation of vaccines between providers. PPAG also recommends that continued education and maintaining current knowledge of vaccines and vaccine schedules are vital for pharmacist immunizers. Finally, PPAG believes that pharmacists should be advocates for childhood vaccinations.

Purpose An important goal of medical education is to teach students to use an electronic health record (EHR) safely and effectively. The purpose of this study is to examine medical student accounts of EHR use during their core inpatient clinical clerkships using a national sample. Paper health records (PHRs) are similarly examined. Method An online survey about health record use within the inpatient component of six core clerkships was administered to medical students after they completed Step 2 Clinical Knowledge of the United States Medical Licensing Examination. The sample included 17,202 U.S. medical students graduating between 2012 and 2016. Mean percentages of clerkships in which students engaged in various health record activities were computed, and analysis of variance was used to examine differences. Results The mean percentages of clerkships in which a student accessed or entered information into an EHR increased from 78% to 93% and 59% to 72%, respectively. For students who used an EHR, the mean percentage of clerkships in which they entered information remained constant at 76%. Students entered notes during the majority of their clerkships, with increases over time. However, students entered orders in less than a quarter of their clerkships, with decreases over time. The percentage of clerkships in which students used PHRs was lower and declining. Conclusions Although students used an EHR in the majority of their inpatient core clerkships, they received limited educational experiences related to order and note writing, which could translate into a lack of preparedness for future training and practice.

IntroductionPractice-based research networks (PBRNs) are sustained collaborations between healthcare professionals, researchers and members of the community that develop, conduct and report on research relevant to local needs. While PBRNs have traditionally been focused towards primary care practices and their patients, there has been increasing interest in how they may help facilitate healthcare integration. Yet, little is known on the ways in which PBRNs can best integrate with the broader healthcare system, in particular Advanced Health Research and Translation Centres. The overall project aim is to build a sustainable collaboration between a PBRN and an Advanced Health Research and Translation Centre to generate a research platform suitable for planning, undertaking and translating research to improve care across the healthcare continuum.Methods and analysisWe will use a developmental evaluation design. Our iterative approach will be informed by a programme logic model and consists of: preparation work (pre-implementation assessment, literature review, community and stakeholder engagement), adaptation and building for a sustainable collaboration (strategy for recruitment and sustainment of members) and planning for network action (designing and implementing priority initiatives, monitoring and follow-up).Ethics and disseminationThis project was approved by the Monash Health ethics committee (ERM Reference Number: 76281; Monash Health Ref: RES-21-0000-392L) and the Monash University Human Research ethics committee (Reference Number: 29786). Dissemination will take place via various channels, including relevant national and international committees and conferences, peer-reviewed journals and social media. Continuous dissemination to and communication with all participants in this project as well as other relevant stakeholders will help strengthen and sustain the network.

SummaryWith the adoption of Computerized Patient Order Entry (CPOE), many physicians – particularly consultants and those who are affiliated with multiple hospital systems – are faced with the challenge of learning to navigate and commit to memory the details of multiple EHRs and CPOE software modules. These physicians may resist CPOE adoption, and their refusal to use CPOE presents a risk to patient safety when paper and electronic orders co-exist, as paper orders generated in an electronic ordering environment can be missed or acted upon after delay, are frequently illegible, and bypass the Clinical Decision Support (CDS) that is part of the evidence-based value of CPOE.We defined a category of CPOE Low Frequency Users (LFUs) – physicians issuing a total of less than 10 orders per month – and found that 50.4% of all physicians issuing orders in 3 urban/suburban hospitals were LFUs and actively issuing orders across all shifts and days of the week. Data are presented for 2013 on the number of LFUs by month, day of week, shift and facility, over 2.3 million orders issued.A menu of 6 options to assist LFUs in the use of CPOE, from which hospital leaders could select, was instituted so that paper orders could be increasingly eliminated. The options, along with their cost implications, are described, as is the initial option selected by hospital leaders. In practice, however, a mixed pattern involving several LFU support options emerged. We review data on how the option mix selected may have impacted CPOE adoption and physician use rates at the facilities. The challenge of engaging LFU physicians in CPOE adoption may be common in moderately sized hospitals, and these options can be deployed by other systems in advancing CPOE pervasiveness of use and the eventual elimination of paper orders.

The internal audit activity must be independent, and internal auditors must be objective in performing their work. The chief audit executive must report to a level within the organization that allows the internal audit activity to fulfill its responsibilities. The chief audit executive must confirm to the board, at least annually, the organizational independence of the internal audit activity. The chief audit executive must communicate and interact directly with the board. The chief audit executive must report periodically to senior management and the board on the internal audit activity’s purpose, authority, responsibility, and performance relative to its plan and on its conformance with the Code of Ethics and the Standards. Reporting must also include International Standards for the Professional Practice of Internal Auditing (Standards). Significant risk and control issues, including fraud risks, governance issues, and other matters that require the attention of senior management and/or the board.

Vaccination rates of children in the United States remain below the target coverage levels identified in the Healthy People 2020 objectives. Given the success of pharmacists in providing adult vaccinations and the accessibility of pharmacists to the public, expanding pharmacists' authority to vaccinate children may improve vaccination rates of children, particularly in key disease states. This article serves as a Position Statement of the Pediatric Pharmacy Advocacy Group (PPAG), who supports the expansion of pharmacists' authority to vaccinate children. PPAG also believes that increased use of state vaccination registries by pharmacists will help improve communication and documentation of vaccines between providers. PPAG also recommends that continued education and maintaining current knowledge of vaccines and vaccine schedules are vital for pharmacist immunizers. Finally, PPAG believes that pharmacists should be advocates for childhood vaccinations.

This is the first in a series of papers reporting Sustainability in Health care by Allocating Resources Effectively (SHARE). The SHARE Program is an investigation of concepts, opportunities, methods and implications for evidence-based investment and disinvestment in health technologies and clinical practices in a local healthcare setting. The papers in this series are targeted at clinicians, managers, policy makers, health service researchers and implementation scientists working in this context. This paper presents an overview of the organisation-wide, systematic, integrated, evidence-based approach taken by one Australian healthcare network and provides an introduction and guide to the suite of papers reporting the experiences and outcomes.

As I am writing this editorial, the United States is preparing for the presidential election. I have no appetite to talk about this particular election, but I would like to share some of my thought...

Purpose Over 20 years ago the term non-specific low back pain became popular to convey the limitations of our knowledge of the pathological source of most people's low back pain. Knowledge of underlying pathology has advanced little since then, despite limited improvements in outcomes for patients with low back pain. Methods This paper discusses potential misunderstandings related to diagnostic studies in the field of low back pain and argues that future diagnostic studies should include and investigate pathological sources of low back pain. Results Six potential misunderstandings are discussed. (1) Until diagnosis is shown to improve outcomes it is not worth investigating; (2) without a gold standard it is not possible to investigate diagnosis of low back pain; (3) the presence of pathology in some people without low back pain means it is not important; (4) dismissal of the ability to diagnose low back pain in clinical guidelines is supported by the same level of evidence as recommendations for therapy; (5) suggesting use of a diagnostic test in research is misinterpreted as endorsing its use in current clinical practice; (6) we seem to have forgotten the 'bio' in biopsychosocial low back pain. Conclusions We believe the misunderstandings presented in this paper partly explain the lack of investigation into pathology as an important component of the low back pain experience. A better understanding of the biological component of low back pain in relation, and in addition, to psychosocial factors is important for a more rational approach to management of low back pain.

With the United States national goal and incentive program to transition from paper to electronic health records (EHRs), healthcare organizations are increasingly implementing EHRs and other related health information technology (IT). However, in institutions which have long adopted these computerized systems, such as the Veterans Health Administration, healthcare workers continue to rely on paper to complete their work. Furthermore, insufficient EHR design also results in computer-based workarounds. Using direct observation with opportunistic interviewing, we investigated the use of paper- and computerbased workarounds to the EHR with a multi-site study of 54 healthcare workers, including primary care providers, nurses, and other healthcare staff. Our analysis revealed several paper- and computer-based workarounds to the VA’s EHR. These workarounds, including clinician-designed information tools, provide evidence for how to enhance the design of the EHR to better support the needs of clinicians.

Aim: Electronic health record (EHR) data have great potential for reuse in research and patient care quality improvement initiatives. However, in dual systems, where both electronic and paper health records are used, inconsistencies and errors may occur. The objective of this study was to determine the degree of agreement between EHR clinical data and paper records for reuse in clinical oral health research and quality improvement initiatives. Methods: A random sample of 200 EHRs for adolescents from eight Area Health Services was obtained from the Information System for Oral Health New South Wales database of 29 599 records, and compared with 200 paper records for adolescents that were stored at clinics. The records were analysed for data reliability. The electronic records were percentage weighted to reflect the number of adolescents treated in each of the Area Health Services. Results: The results showed an overall 95.0% agreement between the 200 individual EHRs and the 200 clinic-stored paper records. In 1.5% of cases, information contained in the paper record was not uploaded into the EHR, and in 3.5% of cases, information contained in the EHR was missing from the paper record. Conclusions: It is possible to conclude that more deficiencies occurred in paper records compared with EHRs. These deficiencies should be taken into account if EHRs are to be reused for clinical oral health research or quality improvement initiatives. Considering the missing data and the great strides in information system technology, it would be logical to adopt one system, with a focus on electronic records to replace the paper records.

There is a need to develop an accreditation process for South African physicians who practise perioperative echocardiography. International level accreditation will bring legitimacy to the process of training practitioners in perioperative echocardiography and ensure standards of practice. Accreditation will be developed as a two-year process during which candidates with a College Fellowship or MMed degree may register with a supervisor and submit a portfolio of 120 comprehensive echo reports and five complete digital studies for assessment. If these are judged to be of an adequate standard, the candidate will be eligible to sit an exam consisting of a multiple-choice question theory and echo video paper and an oral exam.

The CONSORT statement for the full reporting of clinical trials should be consistently applied Although current European League Against Rheumatism (EULAR)1 and American College of Rheumatology (ACR)2 guidelines both support paracetamol (acetaminophen) as the first line oral analgesic for patients with knee osteoarthritis (OA), until now there has been a paucity of clinical trial data to confirm the efficacy of paracetamol in large joint OA. This issue of the Annals is unique in containing one meta-analysis and two large placebo controlled studies that examine evidence for the efficacy of paracetamol in OA. Never in the 127 years of paracetamol’s existence have so much trial data on OA been reported. Because of the marked placebo effect in pain trials3 comparison with a placebo is clearly important to determine the true efficacy of any analgesic. Therefore it is surprising that despite the widespread use and support of paracetamol in OA until now there have been only four placebo controlled trials of this drug in OA. The first two studies reported in 19834 and in 19955 both demonstrated the superiority of paracetamol over placebo for pain relief in large joint OA using parallel group designs. However, the first study contained only 25 patients with knee OA followed up for just 6 weeks.4 The second study was larger (60 patients) but was of just 1 week’s duration and contained a mixed population with knee or hip OA.5 A third parallel group study was reported in 2003.6 This compared paracetamol, diclofenac, and placebo over a 12 week period in 82 patients with knee OA but was the first negative study for paracetamol, showing no difference between paracetamol and placebo using Western Ontario McMaster Osteoarthritis Index (WOMAC) assessments. Most recently, Pincus et al carried out a crossover study …

Background It has been shown that implementation of electronic medical records (EMR) and withdrawal of the paper-based medical record is feasible, but represents a drastic change in the information environment of hospital physicians. Previous investigations have revealed considerable inter-hospital variations in EMR system use and user satisfaction. The aim of this study was to further explore changes of clinicians' work after the EMR system implementation process and how they experienced working in a paper-deprived information environment. Methods Qualitative study based on 18 semi-structured interviews with physicians in two Norwegian hospitals. Results Ten different but related characteristics of work within the EMR-based practice were identified; (1) there was closer clinical and administrative cooperation during the implementation processes; (2) there were greater benefits when everybody used the system; (3) systems supported freshmen better than experienced physicians; (4) the EMR was useful in regard to professional learning; (5) new users were given an introduction to the system by experienced; (6) younger clinicians reported different attitudes than senior clinicians, but this might be related to more than age and previous experience with computers; (7) the EMR made it easier to generate free-text notes, but this also created a potential for information overflow; (8) there is little or no support for mobile work; (9) instances of downtime are still experienced, and this influenced the attitude towards the system and (10) clinicians preferred EMR-only compared to combined paper and electronic systems. Conclusion Despite the removal of paper-based records from clinical workflow (a change that hospital clinicians perceived as highly useful), many of the old routines remained unchanged, limiting the potential of the EMR system. Thus, there is a need to not only remove paper in the physical sense, but also to established routines to fully achieve the benefits of an EMR system.

Objective: This study aims to investigate the mechanism of long non-coding RNA NNT-AS1 in the proliferation of estrogen-mediated endometrial carcinoma (EC). Materials and methods: NNT-AS1, miR-30c, and Nucleophosmin 1 (NPM1) expressions were measured by quantitative real-time PCR and Western blotting. Cell Counting Kit-8 assay and 5-Ethynyl-2'-deoxyuridine (EdU) assay were used to detect the viability and proliferation of Ishikawa and HEC-1-A cells, respectively. RNA immunoprecipitation assay was used to confirm the interaction between NNT-AS1 and miR-30c. Luciferase reporter assay was performed to confirm the interaction between miR-30c and NPM1. Results: NNT-AS1 and NPM1 expressions in EC tissues and cell lines were higher than in benign endometrium and normal endometrial epithelial cells (EECs). miR-30c expression in EC tissues and cell lines was lower than in benign endometrium and normal EECs. NNT-AS1 interacted with miR-30c, and miR-30c negatively regulated NPM1 expression. Overexpression of NNT-AS1 increased NPM1 expression in EC cells, while overexpression of miR-30c reversed the effect. NNT-AS1 interference inhibited the mRNA level of NPM1, while the miR-30c inhibitor reversed the result. Estradiol (E2) promoted the proliferation of EC cells, small interfering RNA (siRNA) against NNT-AS1 inhibited EC cell proliferation, miR-30c inhibitor promoted cell proliferation, and NPM1 siRNA inhibited cell proliferation. E2 increased tumor volume, and NNT-AS1 interference reduced tumor volume in vivo. Conclusion: NNT-AS1 promoted the proliferation of estrogen-mediated EC by regulating miR-30c/NPM1.

Suomi tavoittelee digitalisaation edelläkävijyyttä uudistamalla julkisten palvelujen prosesseja ja sähköistämällä palveluja. Terveydenhuollossa sähköisten asiointipalvelujen käyttöönotolla tavoitellaan yhä parempia terveydenhuollon palveluita ja kustannushyötyjä. Sähköisten asiointipalveluiden käyttö on viime vuosina lisääntynyt, mutta käyttömäärä on edelleen alhainen digitalisaation toteutumiseksi. Sähköisten asiointipalveluiden käytön lisääntymisen yhdeksi haasteeksi on havainnoitu hoitoprosessien uudistamattomuus. Etelä-Pohjanmaan sähköisten asiointipalveluiden parantamiseksi, tämän tutkimuksen tavoitteena oli selvittää, miten terveydenhuollon hoitoprosessit huomioidaan sähköisten asiointipalveluiden kehittämistyössä Etelä-Pohjanmaalla. Tavoitteen saavuttamiseksi tutkittiin, millaisia sähköisiä asiointipalveluja terveydenhuollossa on käytössä ja kehitteillä, millaiseksi sähköisten asiointipalveluiden käytön yleisyys arvioidaan, millainen sähköisten asiointipalveluiden ja terveydenhuollon hoitoprosessien yhteenliittymä on, millä tavoin sähköisten asiointipalveluiden kehittämistyötä toteutetaan ja mitkä ovat Covid-19-pandemian vaikutukset sähköisiin asiointipalveluihin terveydenhuollossa. Tutkimuksen lähtökohta kuvattiin kirjallisuuskatsauksella, jossa haettiin tietoa terveydenhuollon sähköisistä palveluista Pohjoismaista. Tiedot terveydenhuollon hoitoprosessien huomioimisesta sähköisten asiointipalveluiden kehittämistyössä kerättiin terveydenhuollon ja tietohallinnon ammattilaisten haastatteluista. Terveydenhuollossa on käytössä erilaisia sähköisiä asiointipalveluja, joita on tarpeen kehittää sujuvamman asiointikokemuksen mahdollistamiseksi. Sähköisten asiointipalveluiden käyttöönottojen yhteydessä tehdään muutoksia hoitoprosesseihin, mutta prosesseja ei uudisteta suunnittelemalla, miten sähköisten palvelujen hyödyt saavutetaan. Sähköisten asiointipalveluiden kehittämistyötä toivottiin edistettävän ja sisällyttämään työhön prosessisuunnittelu entistä vahvemmin. Sähköisten palveluiden ja prosessien muotoilulle yhtenäiseksi kokonaisuudeksi on olemassa hyvät edellytykset. Tulevaisuudessa on tärkeää määritellä sähköisten asiointipalveluiden hyötytavoitteet ja tehdä strategia niiden saavuttamiseksi. Sähköisten asiointipalveluiden hyödyt konkretisoituvat, kun määritellyt prosessivaiheet digitalisoidaan siten, että ne ovat osa työkäytänteitä ja kansalaisten asiointia., Finland aims to be a pioneer in digitalization by reforming the processes of public services and digitalizing services. In healthcare, the introduction of digital transaction services is aimed at bettering health care services and cost benefits. The use of digital transaction services in recent years has increased, but the realization of digitalization is still low. One of the challenges in increasing the use of digital transaction services is the non-renewable state of the care processes. In order to improve digital services in Southern Ostrobothnia, this study aimed to find out how healthcare processes are taken into account in the development of digital services in Southern Ostrobothnia. In order to achieve this goal, studies were performed to find out what kind of digital services are being used and developed in healthcare, the prevalence of these digital services, how the consortium of e-services and health care processes is being developed, how the development of e-services is being carried out, and what the effects of the Covid-19 pandemic are on e-services in healthcare. The basis of the study is described in a literature review, in which information was sought on digital health services in the Nordic countries. Information on the consideration of health care processes in the development of digital transaction services was collected from interviews with health care and information management professionals. There are several different electronic transaction services in healthcare, which need to be developed for the possibility of a smoother transaction experience. In deploying digital services, care processes will be modified, but these processes are not being redesigned to ensure that the benefits of the digital services can be achieved. It was desired that the development of digital transaction services would be advanced and to include process planning more firmly in the development process. There are good preconditions for formulating electronic transaction services and processes into a unified whole. In the future, it will be important to define the benefit of goals for digital services and to craft a strategy to achieve them. The benefits of digital transaction services materialize when defined processes are digitalized in such a way that they are part of working practices and citizens' transactions.

Background Gout treatment is not optimized globally, often due to therapeutic inertia by physicians or poor adherence to urate-lowering medications by patients. A patient decision aid (PDA) to facilitate shared decision making (SDM) in gout treatment may overcome these physician-patient barriers. Objective The study explored the views of physicians and patients on a novel locally designed gout treatment PDA prototype. Design Qualitative descriptive design was used to gather data from in-depth-interviews (IDI) and focus group discussions (FGD). Data analysis was via thematic analysis. Emergent themes shaped a revised version of the PDA. Setting and participants Adult Asian patients with recent acute gout exacerbations and local Primary Care Physicians (PCP) in Singapore were purposefully chosen. 15 patients with gout and 11 PCPs participated across three IDIs and six FGDs, with the investigators exploring their views of a prototype gout treatment PDA. Results Patients and physicians generally concurred with the content and design of the PDA prototype. However, while patients preferred fewer treatment details, the PCPs desired more information. Patients preferred the display of statistics, while PCPs felt that numbers were not relevant to patients. The latter were hesitant to include treatment options that were unavailable in primary care. Both stakeholders indicated that they would use the PDA during a consultation. PCPs would need further training in SDM, given a lack of understanding of it. Conclusion and patient contribution Patients will be the prime users of the PDA. While their views differed partially from the physicians, both have jointly developed the novel gout treatment PDA.

Recent studies have reported that CGI-58 played an important role in carcinogenesis and tumoral progression in several cancers. In this study, we investigated the expression and prognostic value of CGI-58 in patients with endometrail cancer. Initially, the expression of CGI-58 was analyzed in 552 cases of endometrial carcinoma from The Cancer Genome Atlas (TCGA). Then, the mRNA level of CGI-58 from 32 normal endometrium and 40 endometrial cancer tissues was determined using real-time PCR. In addition, immunohistochemical staining of CGI-58 was performed in 140 endometrial specimens including 35 normal endometrial tissues, 25 atypical endometrial hyperplasia and 80 endometrial cancers. The expression of CGI-58 was significantly up-regulated in endometrial cancer tissues compared with normal endometrial tissue both in TCGA database and clinical cohorts. Over-expression of CGI-58 was significantly correlated with poor histological differentiation. Furthermore, high levels of CGI-58 expression were significantly associated with shorter overall survival for all analyzed cases. Our findings demonstrate that CGI-58 is up-regulated in endometrial cancer and high CGI-58 expression is a poor prognostic marker for endometrial cancer. CGI-58 may be a potential contributor to endometrial cancer oncogenesis and progression.

Cytoplasmic male sterility (CMS) is a maternally inherited trait that causes dysfunctions in pollen and anther development. CMS is caused by the interaction between nuclear and mitochondrial genomes. A product of a CMS-causing gene encoded by the mitochondrial genome affects mitochondrial function and the regulation of nuclear genes, leading to male sterility. In contrast, the RESTORER OF FERTILITY gene (Rf gene) in the nuclear genome suppresses the expression of the CMS-causing gene and restores male fertility. An alloplasmic CMS line is often bred as a result of nuclear substitution, which causes the removal of functional Rf genes and allows the expression of a CMS-causing gene in mitochondria. The CMS/Rf system is an excellent model for understanding the genetic interactions and cooperative functions of mitochondrial and nuclear genomes in plants, and is also an agronomically important trait for hybrid seed production. In this review article, pollen and anther phenotypes of CMS, CMS-associated mitochondrial genes, Rf genes, and the mechanism that causes pollen abortion and its agronomical application for rice are described.

A workflow to expand crystallographic fragment hits to higher affinity compounds using readily available analogs is described and successfully applied., In recent years, crystallographic fragment screening has matured into an almost routine experiment at several modern synchrotron sites. The hits of the screening experiment, i.e. small molecules or fragments binding to the target protein, are revealed along with their 3D structural information. Therefore, they can serve as useful starting points for further structure-based hit-to-lead development. However, the progression of fragment hits to tool compounds or even leads is often hampered by a lack of chemical feasibility. As an attractive alternative, compound analogs that embed the fragment hit structurally may be obtained from commercial catalogs. Here, a workflow is reported based on filtering and assessing such potential follow-up compounds by template docking. This means that the crystallographic binding pose was integrated into the docking calculations as a central starting parameter. Subsequently, the candidates are scored on their interactions within the binding pocket. In an initial proof-of-concept study using five starting fragments known to bind to the aspartic protease endothiapepsin, 28 follow-up compounds were selected using the designed workflow and their binding was assessed by crystallography. Ten of these compounds bound to the active site and five of them showed significantly increased affinity in isothermal titration calorimetry of up to single-digit micromolar affinity. Taken together, this strategy is capable of efficiently evolving the initial fragment hits without major synthesis efforts and with full control by X-ray crystallography.

Introduction Stent insertion is the most frequently used option to treat malignant biliary obstruction (MBO) patients. Hilar cholangiocarcinoma (HCCA) is the most common disease that causes hilar MBO. Aim To assess the clinical efficacy and long-term outcomes of I-125 seed-loaded stent (ISS) insertion for HCCA patients. Material and methods Consecutive patients with HCCA underwent either normal stent (NS) or ISS insertion between January 2017 and December 2019. The baseline and treatment data of these two groups were compared. Results During the period, a total of 93 patients with inoperable HCCA were divided into either NS (n = 48) or ISS (n = 45) insertion groups at our centre. Technical success rates of the NS and ISS insertion were 91.7% and 95.6%, respectively (p = 0.733). Clinical success rates were 93.2% and 100% in the NS and ISS groups, respectively (p = 0.24). Stent dysfunction was observed in 11 and 8 patients in the NS and ISS groups, respectively (p = 0.47). The median stent patency was 143 days and 208 days in the NS and ISS groups, respectively (p < 0.001). All patients died in the follow-up period, with median survival duration of 178 days and 220 days in the NS and ISS groups, respectively (p < 0.001). ISS insertion was the only predictor of longer patency (p = 0.002) and survival (p = 0.01). Conclusions ISS insertion might achieve longer patency and overall survival in patients with inoperable HCCA as compared with NS insertion.

Objective:A high-fibre diet is associated with a lower risk for diseases. However, few adults meet the dietary fibre recommendation. Therefore, the effects and acceptance of an algorithm-generated personalised dietary advice (PDA) compared with general advice (GA) on fibre intake were investigated.Design:A 6-week, single-blind randomised controlled trial with a 3-month follow-up.Setting:PDA was based on habitual intake and provided fibre-rich alternatives using a website; GA contained brochures. Dietary intake was assessed at baseline, week 1, week 6 and 3-month follow-up. Both groups evaluated their advice at week 6. All participants had access to PDA from week 7 until 3-month follow-up.Participants:Two groups of healthy adults: PDA (n 34) and GA (n 47). For 3-month follow-up analysis, participants were re-divided into visitors (n 52) and non-visitors (n 26) of the PDA.Results:At week 6, energy intake remained stable in both groups, but fibre intake per 1000 kcal increased non-significantly in both groups (PDA = Δ0·5 ± 2·8; GA = Δ0·8 ± 3·1, P = 0·128). Importantly, a significantly higher percentage of PDA participants adhered to the recommendation compared with week 1 (PDA = 21 % increase; GA = 4 % increase, P ≤ 0·001). PDA participants evaluated the advice significantly better compared with GA participants. At 3-month follow-up, fibre intake increased compared with baseline (visitors = Δ2·2 ± 2·6, P < 0·001; non-visitors = Δ1·5 ± 1·9, P = 0·001), but was insignificantly different between groups. Visitors had a decrease and non-visitors had an increase in energy intake (visitors =Δ − 132 ± 525; non-visitors = Δ109 ± 507, P = 0·055).Conclusions:The algorithm-generated PDA was well accepted and stimulated adherence to the recommendations more than GA, indicating to be a suitable and cost-efficient method for improving dietary fibre intake in healthy adults.

Long noncoding RNAs (lncRNAs) have been implicated in the progression of malignant tumors, including in clear cell renal cell carcinoma (ccRCC). However, the function and the specific mechanism of lncRNA nicotinamide nucleotide transhydrogenase antisense RNA 1 (NNT-AS1) in ccRCC remains unknown. Thus, this study explored the role of NNT-AS1 in ccRCC. We evaluated NNT-AS1 expression in ccRCC specimens. Next, CCK-8 and Transwell assays were used to evaluate cell proliferation and metastatic abilities. The interaction between miR-137 and NNT-AS1 or Y-box binding protein 1 (YBX-1) was confirmed using a dual luciferase reporter assay. The results showed that NNT-AS1 was significantly upregulated in ccRCC specimens compared with normal tissues. Inhibition of NNT-AS1 restrained ccRCC proliferation and metastasis. Mechanistically, NNT-AS1 acted as a competitive endogenous RNA to sponge miR-137, which depressed ccRCC cells proliferation and metastasis. Moreover, with the use of bioinformatics analysis, the famous oncogene YBX-1 was selected as the potential target of miR-137. Luciferase assay also confirmed the interaction between miR-137 and YBX-1. Further functional studies demonstrated that the inhibition effect of NNT-AS1 knockdown on ccRCC carcinogenesis could be partially reversed by overexpression of YBX-1, suggesting that NNT-AS1 promotes ccRCC progression through the miR-137/YBX-1 pathway. In summary, these findings indicate that NNT-AS1 promotes ccRCC progression via the miR-137/YBX-1 pathway, which may provide a promising therapeutic target for renal cell carcinoma.

The Patient Assessment for Low Back Pain–Symptoms is a newly developed patient-reported outcome instrument to assess specific symptoms of chronic low back pain for use in clinical trials and practice., We describe the mixed-methods (qualitative and quantitative) development and preliminary validation of the Patient Assessment for Low Back Pain–Symptoms (PAL-S), a patient-reported outcome measure for use in chronic low back pain (cLBP) clinical trials. Qualitative methods (concept elicitation and cognitive interviews) were used to identify and refine symptom concepts and quantitative methods (classical test theory and Rasch measurement theory) were used to evaluate item- and scale-level performance of the measure using an iterative approach. Patients with cLBP participated in concept elicitation interviews (N = 43), cognitive interviews (N = 38), and interview-based assessment of paper-to-electronic mode equivalence (N = 8). A web-based sample of patients with self-reported cLBP participated in quantitative studies to evaluate preliminary (N = 598) and revised (n = 401) drafts and a physician-diagnosed cohort of patients with cLBP (N = 45) participated in preliminary validation of the measure. The PAL-S contained 14 items describing symptoms (overall pain, sharp, prickling, sensitive, tender, radiating, shocking, shooting, burning, squeezing, muscle spasms, throbbing, aching, and stiffness). Item-level performance, scale structure, and scoring seemed to be appropriate. One-week test–retest reproducibility was acceptable (intraclass correlation coefficient 0.81 [95% confidence interval, 0.61-0.91]). Convergent validity was demonstrated with total score and MOS-36 Bodily Pain (Pearson correlation −0.79), Neuropathic Pain Symptom Inventory (0.73), Roland-Morris Disability Questionnaire (0.67), and MOS-36 Physical Functioning (−0.65). Individual item scores and total score discriminated between numeric rating scale tertile groups and painDETECT categories. Respondent interpretation of paper and electronic administration modes was equivalent. The PAL-S has demonstrated content validity and is potentially useful to assess treatment benefit in cLBP clinical trials.

Supplemental Digital Content is Available in the Text. Using health administrative data to measure Low back pain underestimates low back pain prevalence among adults and can lead to misclassification bias that is likely nondifferential., Low back pain (LBP) is a high-burden condition that lacks routine surveillance data. Health administrative data may be used for surveillance, but their validity for measuring LBP in the general population has not been established. We aimed to (1) determine the validity of health administrative data to measure LBP compared to self-reported LBP in a population-based sample of Ontario adults; and (2) describe the differences in characteristics of LBP cases based on data sources. Adult respondents (≥18 years) of the Canadian Community Health Survey (CCHS) from 2003 to 2012 were included (N = 150,695). Canadian Community Health Survey data were individually linked to health administrative data, including Ontario Health Insurance Plan and hospitalization data. The reference standard was defined as self-reported back problem diagnosed by a health professional in the CCHS. Measurement of LBP from billing records was defined as ≥1 physician billing or procedural code for LBP during the year preceding CCHS interview date. We measured concurrent validity by comparing prevalence, agreement (kappa), and accuracy (sensitivity, specificity, and positive and negative predictive values [PV]) of administrative data to measure LBP. Prevalence of LBP was higher using self-reported (21.2%) than administrative data (10.2%), and agreement was low (kappa = 0.21). Administrative data had sensitivity 23.9% (95% CI 23.1-24.6), specificity 93.4% (95% CI 93.2-93.7), positive PV 50.4% (95% CI 49.1-51.7), and negative PV 82.0% (95% CI 81.7-82.3). Characteristics of LBP cases based on data sources differed in sex, health/behaviour characteristics, and allied health care utilization. Using health administrative data significantly underestimates the prevalence of LBP. This can lead to misclassification bias that is likely nondifferential in epidemiological studies.

Background: The pressure of pursuing an athletic career simultaneously with education may set adolescent student-athletes at risk for sport and school burnout. Although the 2 life domains of student-athletes are strongly intertwined, so far, there has not been an instrument for investigating sport burnout parallel to school burnout. The aim of the present study was to introduce a sport burnout measure for adolescents in a dual career context and investigate its validity and reliability by using confirmatory factor analysis. Methods: The participants were 391 student-athletes (51% females) who filled in a questionnaire of sport burnout and background variables in the beginning of upper secondary school. Results: A 3-factor model or a second-order-factor model described the data better and gave better reliability indices than a 1-factor model. The 3 dimensions of sport burnout were shown to be separate, but closely related constructs. Evidence for convergent and discriminant validity was obtained by correlating the 3 sport burnout dimensions with depressive symptoms, self-esteem, and sport task values. Conclusion: The results suggest that Sport Burnout Inventory-Dual Career Form (SpBI-DC) is a valid and reliable instrument for investigating sport burnout among adolescent student-athletes.

Purpose: With the rapid expansion of the field of interventional neuroradiology (INR) and the diverse background of aspiring neuro-interventionists, there is an ever increasing need to establish consensus criteria for training and accreditation in INR.Materials and Methods: We performed a survey to explore the current state of criteria for training and accreditation in INR. The questionnaire consisting of 11 questions was emailed to the members of World Federation of Interventional and Therapeutic Neuroradiology (WFITN) worldwide. It was focused on the training charter, training program, qualifying examination, and education after training program as perceived by practitioners in each country.Results: A total of 52 WFITN members in 19 countries responded to the questionnaire. There was a huge variation internationally and nationally due to the unique situation and challenges in each country and institution. Criteria for training and accreditation in INR were well established in some countries of Europe, North America, and Asia but not specified in other countries.Conclusion: It is critical to establish consensus criteria for training and accreditation in INR in order to ensure safe practice and continued expansion and development of INR as a specialty.

Intervertebral disc degeneration (IDD) is the main cause of lower back pain (LBP), and puzzles massive individuals worldwide. Mesenchymal stem cells (MSCs) transplantation has been demonstrated to potentially ameliorate IDD progression, while the underlying mechanism has not been fully explained. Interleukin-1β (IL-1β) was used to induce nucleus pulposus cells (NPCs) injury. Bone marrow MSCs-derived exosomes were isolated using the super centrifugation method, and characterized using Transmission electron microscopy (TEM) and western blot. Cell viability was determined by MTT, while apoptosis was measured by Annexin-V staining using flow cytometry. miR-142-3fp and gene expressions were measured by real-time PCR. The protein expressions were determined by western blot. Herein, we found exosomes from bone marrow MSCs are circular vesicles, about 80 nm in diameter, and with robust expression of TSG101 and CD63, but without of Calnexin. MSCs exosomes alleviated NPCs apoptosis by reducing IL-1β-induced inflammatory cytokines secretion and MAPK signaling activation. Additionally, MSCs exosomes inhibited NPCs apoptosis and MAPK signaling by delivering miR-142-3p that targets mixed lineage kinase 3 (MLK3). Overexpression of MLK3 abolished the effects of MSCs exosomes on the inflammatory condition, cell apoptosis, and MAPK signaling activation in NPCs. The results confirmed that bone marrow MSCs-derived exosomes-packaged miR-142-3p alleviates NPCs injury through suppressing MAPK signaling by targeting MLK3. The work highlights the therapeutic effect of MSCs on IDD progression, and bone marrow MSCs exosomes might be apromising therapeutic strategy for IDD.

Background Cholangiocarcinoma (CCA) is a serious malignant tumor. Long non-coding RNA NNT-AS1 (NNT-AS1) takes crucial roles in several tumors. So, we planned to research the roles and underlying mechanism of NNT-AS1 in CCA. Results NNT-AS1 overexpression was appeared in CCA tissues and cell lines. Proliferation was promoted by NNT-AS1 overexpression in CCLP1 and TFK1 cells. Besides, NNT-AS1 overexpression reduced E-cadherin level and raised levels of N-cadherin, vimentin, Snail and Slug. However, the opposite trend was occurred by NNT-AS1 knockdown. Further, NNT-AS1 overexpression promoted phosphatidylinositol 3 kinase (PI3K)/AKT and extracellular signal-regulated kinase (ERK)1/2 pathways. MiR-203 was sponged by NNT-AS1 and miR-203 mimic reversed the above promoting effects of NNT-AS1. Additionally, insulin-like growth factor type 1 receptor (IGF1R) and zinc finger E-box binding homeobox 1 (ZEB1) were two potential targets of miR-203. Conclusion NNT-AS1 promoted proliferation, EMT and PI3K/AKT and ERK1/2 pathways in CCLP1 and TFK1 cells through down-regulating miR-203. Methods CCLP1 and TFK1 cells were co-transfected with pcDNA-NNT-AS1 and miR-203 mimic. Bromodeoxyuridine (BrdU), flow cytometry, quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot were employed to detect roles and mechanism of NNT-AS1. Interaction between NNT-AS1 and miR-203 or miR-203 and target genes was examined through luciferase activity experiment.

Highlights • Surgical randomized controlled trials (RCT) have unique design and analytic challenges. • Surgical RCTs often drive clinical and operative decision making. • To date, a comprehensive analysis of surgical RCTs across multiple specialties has not been completed. • We aim to identify issues with surgical RCTs, and offer guidance for future direction., Introduction The complexities and risks inherent to the field of surgery and surgical interventions present unique challenges to the design and analysis of surgical randomized controlled trials (RCT). Prior studies have investigated the practical and methodologic challenges posed by surgical RCTs. To date, however, a comprehensive analysis of the contemporary literature across multiple surgical subspecialties does not exist. In this descriptive analysis, we set out to characterize surgical RCTs over the past 10 years across six major surgical specialties. Methods and analysis A literature search by a medical librarian will be performed to identify all surgical randomized clinical trials published between January 2009 and December 2019 in the two journals with the highest impact factor for six surgical specialties as well as two large general medicine journals. Two reviewers will independently screen the citations retrieved from the literature search and extract data according to a previously described protocol via a pre-defined data collection form. Categorical variables will be reported as counts and percentages. Following assessment of normality, continuous variables will be reported as mean (standard deviation) or median (inter-quartile range). Based on normality of data, independent t-test or the Mann-Whitney U test will be used to compare continuous variables and chi-square and Fisher’s exact tests to compare categorical variables. Comparisons across multiple sets will be performed using ANOVA or Kruskak-Wallis tests. Two-sided significance testing will be used and a p-value

The long noncoding RNA nicotinamide nucleotide transhydrogenase antisense RNA 1 (NNT-AS1) is a key malignancy regulator in a variety of human cancers. In this study, we first measured the expression of NNT-AS1 in bladder cancer and examined its role in cancer progression. The mechanisms behind the oncogenic functions of NNT-AS1 in bladder cancer were explored. We found that NNT-AS1 was upregulated in bladder cancer tissues and cell lines. This increased expression demonstrated a significant correlation with advanced clinical stage, lymph node metastasis, and shorter overall survival. NNT-AS1 knockdown suppressed bladder cancer cell proliferation, migration, and invasion and facilitated apoptosis in vitro and hindered tumor growth in vivo. NNT-AS1 functioned as a competing endogenous RNA for microRNA-496 (miR-496), and the suppressive effects of NNT-AS1 knockdown on malignant characteristics were abrogated by miR-496 silencing. HMGB1 was identified as a direct target gene of miR-496 in bladder cancer, and HMGB1 expression was enhanced by NNT-AS1 via sponging of miR-496. In conclusion, the NNT-AS1–miR-496–HMGB1 pathway plays a significant role in the aggressive behavior of bladder cancer and may lead to new NNT-AS1–based diagnostics and therapeutics.

A total of 391 male employees in a Swedish pulp and paper company were followed up for 22 years. As a part of a health examination in 1961 back pain reported by the subjects and abnormalities of the back as judged by the physicians were investigated with respect to predictive power regarding sick leave, early retirement, unemployment, labour turnover, and mortality during the follow up period. Univariate analysis showed that abnormalities of the back were better than back pain for predicting early retirement. Neither back pain nor back abnormalities had any predictive power with respect to long term sick leave, labour turnover, or mortality. Multivariate analyses of 26 variables were performed. Both self assessment of general health and back abnormalities were predictive for early retirement with a diagnosis of back disorder on the retirement certificate but self assessed health was a stronger predictor. Age, smoking, and neuroticism were predictors regarding early retirement for all diagnoses. Education had a negative association; neuroticism did not predict early retirement with a diagnosis of back disorder.

Objectives Parental burnout is a construct that reflects the exhaustion and emotional distancing of parents from their children due to the growing demands of caring for them. Research has pointed to a heightened risk for parental burnout among parents of children with special needs. Additional research has indicated that parents’ personality traits and relational dynamics serve as resiliency factors regarding parental burnout. Methods In the present study, 91 primary parental caregivers of children receiving ongoing treatment at a pediatric ambulatory care unit were recruited. A theoretical model proposing the specific ways in which self-compassion and concern for others complement each other in predicting parental burnout was examined. In this model, the relationships between self-compassion, concern for others, and burnout respectively are mediated by different basic psychological needs, detailed in self-determination theory. Participants completed various questionnaires measuring these constructs. Regression and mediation analyses were used to examine our hypotheses. Results Results indicated that self-compassion and concern for others predicted levels of parental burnout. The covariance between concern for others and burnout was mediated by the psychological need of relatedness. Conclusions The findings support the extension of a three-layered conceptual model of (a) self-compassion and concern for others, (b) psychological needs, and (c) burnout. The present study highlights self-compassion and concern for others as potential resilience factors regarding the risk of burnout in parental caregiving. These findings point to promising avenues for burnout prevention and preemptive facilitation of parental caregiving. Supplementary Information The online version contains supplementary material available at 10.1007/s12671-021-01752-z.

Background Electronic health records (EHRs) are a significant contributor to physicians’ low satisfaction, reduced engagement and increased burnout. Yet the majority of evidence around EHR and physician harms is based on self-reported screen time, which may both over- and underreport actual exposure. Aims The purpose of this study was to examine how objective EHR use correlates with physician well-being and to develop preliminary recommendations for well-being-based EHR interventions. Method Prior to the onset of COVID-19, psychiatry residents and attending physicians working in an out-patient clinic at an academic medical centre provided consent for access to EHR-usage logs and completed a well-being assessment made up of three scales: the Maslach Burnout Inventory, the Urecht Work Engagement Scale and the Professional Quality of Life Measure. Survey responses and objective EHR data were analysed with descriptive statistics. Results Responses were obtained from 20 psychiatry residents (total eligible residents n = 27; 74% participation) and 16 clinical faculty members (total eligible faculty n = 24; 67% participation) with an overall response rate of 71% (total eligible residents and faculty n = 51 and total residents and faculty who completed survey n = 36). Moderate correlations for multiple well-being domains emerged in analysis for all participants, especially around the time spent per note and patient visits closed the same day. Conclusions EHR-usage logs represent an objective tool in the evaluation and enhancement of physician well-being. Results from our pilot study suggest that metrics for note writing efficiency and closing patient visits the same day are associated with physician well-being. These metrics will be important to study in ongoing efforts involving well-being-based EHR interventions.

Objectives Patients who are no longer eligible for curative treatment often suffer from multiple complaints and require a multidisciplinary treatment approach. We incorporated two pharmacists in the palliative team, one hospital pharmacist and one pharmacist who were trained as a community pharmacist. The objective of our study was to evaluate their contribution to the palliative team. Methods During 13 months, the two pharmacists participated in all regular patient reviews and rounds and were available for individual consultation by all members of the palliative team on a daily basis. Each intervention (consults at request or during the patient rounds) was logged and categorised. Key findings During the study period, 115 patients were under the care of the palliative treatment team. The pharmacists were actively involved in 107 of these (93%). Pharmacists interventions occurred in 76% of patients, with an average of 1.5 interventions per patient. The most common intervention types were giving general therapeutic advice, starting of a drug for an uncontrolled symptom and stopping a drug that was given as prophylaxis. When comparing the contribution of the hospital pharmacist and the outpatient pharmacist, their interventions overlapped with regard to starting drugs, choice of drugs and side-effect management. However, interventions on parenteral drugs or optimising the route of administration mostly came from the hospital pharmacist, whereas the outpatient pharmacist more often intervened in increasing adherence and stopping drugs. Conclusion The palliative pharmacist team adds expertise to the palliative treatment team, with an active contribution in 76% of patients.