bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of a single interprofessional simulation session on medical and nursing students’ attitudes toward interprofessional learning and professional identity: a questionnaire study
Authors: Burford Bryan , Greig Paul , Kelleher Mike , Merriman Clair , Platt Alan , Richards Elize , Davidson Neil , Vance Gill
Published: March 2020

Background

Participation in simulation-based interprofessional education (sim-IPE) may affect students’ attitudes towards interprofessional learning (through gaining experience with others) and their professional identity (by increasing the ‘fit’ of group membership). We examined this in two questionnaire studies involving students from four universities in two areas of the UK.

Method

Questionnaire data were collected before and after students took part in a sim-IPE session consisting of three acute scenarios. Questionnaires included the Readiness for Interprofessional Learning Scale (RIPLS) and measures of professional identity derived from the social identity theory literature. In Study 1, only identification with Professional Group (doctor or nurse) was measured, while in Study 2 identification with Student Group (medical or nursing student) and the immediate interprofessional Team worked with in the simulation were also measured.

Linear mixed effects regression analysis examined the effect of the simulation session, and differences between medical and nursing students, sites and identity measures.

Results

A total of 194 medical and 266 nursing students completed questionnaires.

A five-item subset of RIPLS (RIPLSCore) was used in analysis. In both studies RIPLSCore increased for all groups following participation in sim-IPE, although this was larger for nursing students in Study 1. Nursing students had consistently higher RIPLSCore scores than medical students at one site.

Effects of the session on identity varied between sites, and dimensions of identity. Notably, while positive emotions associated with group membership (Ingroup Affect) increased for Student Group, Professional Group and Team, the sense of belonging (Ingroup Ties) and importance (Centrality) of the group increased only for Team. Nursing students had consistently higher identification scores than medical students.

Conclusions

Participation in a sim-IPE session can improve attitudes towards interprofessional learning. It can also enhance professional identity, particularly as related to emotional aspects of group membership, with possible benefits for wellbeing. Changes in identification with the immediate Team suggest positive psychological consequences of ad hoc Team formation in the workplace.

Differences between medical and nursing students suggest their differing opportunities to work with other professions during training may change baseline attitudes and identity. However, a single sim-IPE session can still have an additive effect.
Collaboration with community connectors to improve primary care access for hardly reached people: a case comparison of rural Ireland and Australia
Authors: Wallace Carolyn , Farmer Jane , White Carolynne , McCosker Anthony
Published: March 2020

Background

This study presents a way for health services to improve service access for hardly reached people through an exploration of how staff can find and collaborate with citizens (referred to as connectors) who span socio-cultural boundaries in their community. The study explored the local socio-cultural contexts of connectors’ boundary spanning activities and if they are health related; boundary spanning occurring between connectors and health professionals at the interface of health systems and community; and the opportunities and barriers to actively seeking out and collaborating with community connectors to access marginalised and hardly reached people.

Methods

We conducted a qualitative case comparison from rural Ireland and Australia. Following purposive snow-ball sampling techniques to recruit participants, semi-structured interviews were conducted with 34 community informants, 21 healthcare staff and 32 connectors. Transcripts were coded and analysed using an inductive approach to ascertain categories and overall themes.

Results

We found a diverse sample of connectors relating to heterogenous, small and locally distinct groups of hardly reached people. Overall 26 connectors were active at the interface between health services and the community, with variation in how this occurred between cases. The majority (21) described one or more health related activities with hardly reached people. All connectors expressed a willingness to develop a relationship with local health services on issues they identified as relevant. Barriers to collaborations between connectors and health services related to bureaucracy, workload, and burnout.

Conclusions

Collaborating with connectors has potential as one strategy to improve access to health services for hardly reached people. To enact this, health staff need to identify local socio-cultural boundaries and associated connectors, facilitate two-way connections at the boundary between health services and community and enable collaboration by attending to activities in the community, at the interface between health services and community, and within the health system.
Development of the Inner City attitudinal assessment tool (ICAAT) for learners across Health care professions
Authors: McKinney Mark , Smith Katherine E. , Dong Kathryn A. , Babenko Oksana , Ross Shelley , Kelly Martina A. , Salvalaggio Ginetta
Published: March 2020

Background

Many health professions learners report feeling uncomfortable and underprepared for professional interactions with inner city populations. These learners may hold preconceptions which affect therapeutic relationships and provision of care. Few tools exist to measure learner attitudes towards these populations. This article describes the development and validity evidence behind a new tool measuring health professions learner attitudes toward inner city populations.

Methods

Tool development consisted of four phases: 1) Item identification and generation informed by a scoping review of the literature; 2) Item refinement involving a two stage modified Delphi process with a national multidisciplinary team (n = 8), followed by evaluation of readability and response process validity with a focus group of medical and nursing students (n = 13); 3) Pilot testing with a cohort of medical and nursing students; and 4) Analysis of psychometric properties through factor analysis and reliability.

Results

A 36-item online version of the Inner City Attitudinal Assessment Tool (ICAAT) was completed by 214 of 1452 undergraduate students (67.7% from medicine; 32.3% from nursing; response rate 15%). The resulting tool consists of 24 items within a three-factor model – affective, behavioural, and cognitive. Reliability (internal consistency) values using Cronbach alpha were 0.87, 0.82, and 0.82 respectively. The reliability of the whole 24-item ICAAT was 0.90.

Conclusions

The Inner City Attitudinal Assessment Tool (ICAAT) is a novel tool with evidence to support its use in assessing health care learners’ attitudes towards caring for inner city populations. This tool has potential to help guide curricula in inner city health.
Antecedents of use of e-health services in Central Eastern Europe: a qualitative comparative analysis
Authors: Ćwiklicki Marek , Schiavone Francesco , Klich Jacek , Pilch Kamila
Published: March 2020

Background

The objective of this paper is to identify the key conditions that positively affect the use of e-health services in Central Eastern Europe (CEE) countries. CEE countries after the political and economic transformation in 1989/90 implemented slightly different national health care models. The research question of the study is: how do the various institutional conditions at the national level affect the use of e-health services in CEE countries?

Methods

The e-health description was derived from papers indexed in Web of Science and Scopus. The data for computation were collected from the 2015 global survey by the WHO Global Observatory for eHealth. We used a narrative literature review in order to identify key terms associated to e-health and conditions for the implementation of e-health services. The search terms were “e-health” and “*” where * was particular thematic section of e-health according to WHO GOeH. The inclusion criterion was relevance of the paper to e-health and searched phase. Eligibility criteria for countries for being described as CEE countries: Estonia, Lithuania, Latvia, Poland, Hungary, Romania, Bulgaria, Czech Republic, Slovenia, and Croatia (we omitted Slovakia from the analysis because this country was not covered by the WHO Survey). We applied qualitative comparative analysis (QCA) to analyse the necessary order of conditions. The dependent variable of the study is the national rate of use of e-health services.

Results

QCA shows that legal medical jurisdiction, teleprogramme and electronic health records supplemented by adequate training constitute critical conditions to achieve success in e-health implementation.

Conclusions

We conclude that the more formalised a framework for e-health service delivery is, the more likely it will be used. Therefore formalisation fosters the diffusion, dissemination and implementation of e-health solutions in this area. Formalisation must be accompanied by tailored training for health care professionals and patients. Our analyses are related only to the paths of e-health implementation in CEE countries thus consequently the findings and conclusions cannot be directly applied to other countries. The limitations of this study are related the absence of a broader context of e-health development, including the development of ICT infrastructure and ICT literacy.
Results-based financing as a strategic purchasing intervention: some progress but much further to go in Zimbabwe?
Authors: Witter Sophie , Chirwa Yotamu , Chandiwana Pamela , Munyati Shungu , Pepukai Mildred , Bertone Maria Paola , Banda Steve
Published: March 2020

Background

Results-Based Financing (RBF) has proliferated in the health sectors of low and middle income countries, especially those which are fragile or conflict-affected, and has been presented by some as a way of reforming and strengthening strategic purchasing. However, few if any studies have empirically and systematically examined how RBF impacts on health care purchasing. This article examines this question in the context of Zimbabwe’s national RBF programme.

Methods

The article is based on a documentary review, including 60 documents from 2008 to 2018, and 40 key informant (KI) interviews conducted with international, national and district level stakeholders in early 2018 in Zimbabwe. Interviews and analysis of both datasets followed an existing framework for strategic purchasing, adapted to reflect changes over.

Results

We find that some functions, such as assessing service infrastructure gaps, are unaffected by RBF, while others, such as mobilising resources, are partially affected, as RBF has focused on one package of care (maternal and child health services) within the wider essential health care, and has contributed important but marginal costs. Overall purchasing arrangements remain fragmented. Limited improvements have been made to community engagement. The clearest changes to purchasing arrangements relate to providers, at least in relation to the RBF services. Its achievements included enabling flexible resources to reach primary providers, funding supervision and emphasising the importance of reporting.

Conclusions

Our analysis suggests that RBF in Zimbabwe, at least at this early stage, is mainly functioning as an additional source of funding and as a provider payment mechanism, focussed on the primary care level for MCH services. RBF in this case brought focus to specific outputs but remained one provider payment mechanism amongst many, with limited traction over the main service delivery inputs and programmes. Zimbabwe’s economic and political crisis provided an important entry point for RBF, but Zimbabwe did not present a ‘blank slate’ for RBF to reform: it was a functional health system pre-crisis, which enabled relatively swift scale-up of RBF but also meant that the potential for restructuring of institutional purchasing relationships was limited. This highlights the need for realistic and contextually tailored expectations of RBF.
A clinical decision support system improves antibiotic therapy for upper urinary tract infection in a randomized single-blinded study
Authors: Neugebauer M. , Ebert M. , Vogelmann R.
Published: March 2020

Background

Due to increasing bacterial resistance rates choosing a correct empiric antibiotic therapy is getting more and more complex. Often medical doctors use information tools to make the right treatment choice.

Methods

One hundred sixty six participants (77 medical doctors and 89 medical students) were asked to provide a diagnosis and antibiotic therapy in a simple fictive paper case of upper urinary tract infection (UTI) in a randomized single-blinded study. Participants were randomized to one of four information tools they were allowed to use in the study or control: 1. free internet access, 2. pharmaceutical pocket guide, 3. pocket guide antibiotic therapy, 4. clinical decision support system (CDSS), and control (no information tool). The CDSS was designed for the study. The adherence to the national German UTI guideline was evaluated.

Results

Only 27.1% (n = 45/166) provided a correct diagnosis of upper UTI and 19.4% (n = 32/166) an antibiotic treatment recommended by national German treatment guidelines indicating their need for information tools. This result was not significantly different between medical doctors and medical students, residents and medical specialists or level of working experience. Using CDSS improved results significantly compared to conventional tools (diagnosis 57.1%; treatment recommendation 40.5%; p < 0,01). Processing time was not different between the use of CDSS and conventional information tools. CDSS users based their decision making on their assigned information tool more than users of conventional tools (73.8% vs. 48.0%; p < 0.01). Using CDSS improved the confidence of participants in their recommendation significantly compared to conventional tools (p < 0.01).

Conclusions

Our study suggests that medical professionals require information tools in diagnosing and treating a simple case of upper UTI correctly. CDSS appears to be superior to conventional tools as an information source.
Quantifying the economic cost of antibiotic resistance and the impact of related interventions: rapid methodological review, conceptual framework and recommendations for future studies
Authors: Jit Mark , Ng Dorothy Hui Lin , Luangasanatip Nantasit , Sandmann Frank , Atkins Katherine E. , Robotham Julie V. , Pouwels Koen B.
Published: March 2020

Background

Antibiotic resistance (ABR) poses a major threat to health and economic wellbeing worldwide. Reducing ABR will require government interventions to incentivise antibiotic development, prudent antibiotic use, infection control and deployment of partial substitutes such as rapid diagnostics and vaccines. The scale of such interventions needs to be calibrated to accurate and comprehensive estimates of the economic cost of ABR.

Methods

A conceptual framework for estimating costs attributable to ABR was developed based on previous literature highlighting methodological shortcomings in the field and additional deductive epidemiological and economic reasoning. The framework was supplemented by a rapid methodological review.

Results

The review identified 110 articles quantifying ABR costs. Most were based in high-income countries only (91/110), set in hospitals (95/110), used a healthcare provider or payer perspective (97/110), and used matched cohort approaches to compare costs of patients with antibiotic-resistant infections and antibiotic-susceptible infections (or no infection) (87/110). Better use of methods to correct biases and confounding when making this comparison is needed. Findings also need to be extended beyond their limitations in (1) time (projecting present costs into the future), (2) perspective (from the healthcare sector to entire societies and economies), (3) scope (from individuals to communities and ecosystems), and (4) space (from single sites to countries and the world). Analyses of the impact of interventions need to be extended to examine the impact of the intervention on ABR, rather than considering ABR as an exogeneous factor.

Conclusions

Quantifying the economic cost of resistance will require greater rigour and innovation in the use of existing methods to design studies that accurately collect relevant outcomes and further research into new techniques for capturing broader economic outcomes.
Specific chromatin landscapes and transcription factors couple breast cancer subtype with metastatic relapse to lung or brain
Authors: Cai Wesley L. , Greer Celeste B. , Chen Jocelyn F. , Arnal-Estapé Anna , Cao Jian , Yan Qin , Nguyen Don X.
Published: March 2020

Background

Few somatic mutations have been linked to breast cancer metastasis, whereas transcriptomic differences among primary tumors correlate with incidence of metastasis, especially to the lungs and brain. However, the epigenomic alterations and transcription factors (TFs) which underlie these alterations remain unclear.

Methods

To identify these, we performed RNA-seq, Chromatin Immunoprecipitation and sequencing (ChIP-seq) and Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) of the MDA-MB-231 cell line and its brain (BrM2) and lung (LM2) metastatic sub-populations. We incorporated ATAC-seq data from TCGA to assess metastatic open chromatin signatures, and gene expression data from human metastatic datasets to nominate transcription factor biomarkers.

Results

Our integrated epigenomic analyses found that lung and brain metastatic cells exhibit both shared and distinctive signatures of active chromatin. Notably, metastatic sub-populations exhibit increased activation of both promoters and enhancers. We also integrated these data with chromosome conformation capture coupled with ChIP-seq (HiChIP) derived enhancer-promoter interactions to predict enhancer-controlled pathway alterations. We found that enhancer changes are associated with endothelial cell migration in LM2, and negative regulation of epithelial cell proliferation in BrM2. Promoter changes are associated with vasculature development in LM2 and homophilic cell adhesion in BrM2. Using ATAC-seq, we identified a metastasis open-chromatin signature that is elevated in basal-like and HER2-enriched breast cancer subtypes and associates with worse prognosis in human samples. We further uncovered TFs associated with the open chromatin landscapes of metastatic cells and whose expression correlates with risk for metastasis. While some of these TFs are associated with primary breast tumor subtypes, others more specifically correlate with lung or brain metastasis.

Conclusions

We identify distinctive epigenomic properties of breast cancer cells that metastasize to the lung and brain. We also demonstrate that signatures of active chromatin sites are partially linked to human breast cancer subtypes with poor prognosis, and that specific TFs can independently distinguish lung and brain relapse.
Metatranscriptomic analysis to define the Secrebiome, and 16S rRNA profiling of the gut microbiome in obesity and metabolic syndrome of Mexican children
Authors: Gallardo-Becerra Luigui , Cornejo-Granados Fernanda , García-López Rodrigo , Valdez-Lara Alejandra , Bikel Shirley , Canizales-Quinteros Samuel , López-Contreras Blanca E. , Mendoza-Vargas Alfredo , Nielsen Henrik , Ochoa-Leyva Adrián
Published: March 2020

Background

In the last decade, increasing evidence has shown that changes in human gut microbiota are associated with diseases, such as obesity. The excreted/secreted proteins (secretome) of the gut microbiota affect the microbial composition, altering its colonization and persistence. Furthermore, it influences microbiota-host interactions by triggering inflammatory reactions and modulating the host's immune response. The metatranscriptome is essential to elucidate which genes are expressed under diseases. In this regard, little is known about the expressed secretome in the microbiome. Here, we use a metatranscriptomic approach to delineate the secretome of the gut microbiome of Mexican children with normal weight (NW) obesity (O) and obesity with metabolic syndrome (OMS). Additionally, we performed the 16S rRNA profiling of the gut microbiota.

Results

Out of the 115,712 metatranscriptome genes that codified for proteins, 30,024 (26%) were predicted to be secreted, constituting the Secrebiome of the gut microbiome. The 16S profiling confirmed an increased abundance in Firmicutes and decreased in Bacteroidetes in the obesity groups, and a significantly higher richness and diversity than the normal weight group. We found novel biomarkers for obesity with metabolic syndrome such as increased Coriobacteraceae, Collinsela, and Collinsella aerofaciens; Erysipelotrichaceae, Catenibacterium and Catenibacterium sp., and decreased Parabacteroides distasonis, which correlated with clinical and anthropometric parameters associated to obesity and metabolic syndrome. Related to the Secrebiome, 16 genes, homologous to F. prausniitzi, were overexpressed for the obese and 15 genes homologous to Bacteroides, were overexpressed in the obesity with metabolic syndrome. Furthermore, a significant enrichment of CAZy enzymes was found in the Secrebiome. Additionally, significant differences in the antigenic density of the Secrebiome were found between normal weight and obesity groups.

Conclusions

These findings show, for the first time, the role of the Secrebiome in the functional human-microbiota interaction. Our results highlight the importance of metatranscriptomics to provide novel information about the gut microbiome’s functions that could help us understand the impact of the Secrebiome on the homeostasis of its human host. Furthermore, the metatranscriptome and 16S profiling confirmed the importance of treating obesity and obesity with metabolic syndrome as separate conditions to better understand the interplay between microbiome and disease.
Quality of life, level of functioning, and its relationship with mental and physical disorders in the elderly: results from the MentDis_ICF65+ study
Authors: Grassi Luigi , Caruso Rosangela , Da Ronch Chiara , Härter Martin , Schulz Holger , Volkert Jana , Dehoust Maria , Sehner Susanne , Suling Anna , Wegscheider Karl , Ausín Berta , Canuto Alessandra , Muñoz Manuel , Crawford Mike J. , Hershkovitz Yael , Quirk Alan , Rotenstein Ora , Santos-Olmo Ana Belén , Shalev Arieh , Strehle Jens , Weber Kerstin , Wittchen Hans-Ulrich , Andreas Sylke , Belvederi Murri Martino , Zerbinati Luigi , Nanni Maria Giulia
Published: March 2020

Background

An ageing population worldwide needs to investigate quality of life (QoL) and level of functioning (LoF) in the elderly and its associated variables. We aimed to study the relationship between Quality of Life (QoL) and Level of Functioning (LoF) in an elderly population in Europe.

Method

As part of the Ment_Dis65+ European Project, 3142 community-dwelling adults aged 65–84 years in six countries were assessed by using the adaptation for the elderly of the Composite International Diagnostic Interview (CIDI65+) to provide psychiatric diagnosis according to the International Classification of Diseases (10th edition) (ICD-10 Classification of Mental and Behavioural Disorders). Socio-demographic and clinical interviews, and two self-report tools, the World Health Organization QoL assessment (WHO QoL BREF), to assess QoL, and the WHO Disability Assessment Schedule -II (WHODAS-II), to assess LoF, were also administered.

Results

Most subjects reported good levels of QoL (56.6%) and self-rated health (62%), with no or mild disability (58.8%). There was a linear decrease of the QoL and the LoF by increase of age. Elderly with ICD-10 mental disorder (e.g. somatoform, affective and anxiety disorders) had poorer QoL and lower LoF. There were a number of predictors of lower levels of QoL and disability, including both socio-demographic variables (e.g. male gender, increase in age, poor financial situation, retirement, reduced number of close significant others), ICD-10 psychiatric diagnosis (mainly anxiety, somatoform disorders) and presence of medical disorders (mainly heart and respiratory diseases).

Conclusions

The study indicates that QoL and LoF were quite acceptable in European elderly people. A series of variables, including psychiatric and somatic disorders, as well as socio-demographic factor influenced in a negative way both QoL and LoF. More specific links between mental health, social and health services dedicated to this segment of the population, should be implemented in order to provide better care for elderly people with conditions impacting their QoL and functioning.
Small molecule-induced simultaneous destabilization of β-catenin and RAS is an effective molecular strategy to suppress stemness of colorectal cancer cells
Authors: Cho Yong-Hee , Ro Eun Ji , Yoon Jeong-Su , Kwak Dong-Kyu , Cho Jaebeom , Kang Dong Woo , Lee Ho-Young , Choi Kang-Yell
Published: March 2020

Background

Cancer stem cells (CSCs), the major driver of tumorigenesis, is a sub-population of tumor cells responsible for poor clinical outcomes. However, molecular mechanism to identify targets for controlling CSCs is poorly understood.

Methods

Gene Set Enrichment Analyses (GSEA) of Wnt/β-catenin and RAS signaling pathways in stem-like subtype of colorectal cancer (CRC) patients were performed using two gene expression data set. The therapeutic effects of destabilization of β-catenin and RAS were tested by treatment of small molecule KYA1797K using CRC patient derived cells.

Results

Treatment with KYA1797K, a small molecule that destabilizes both β-catenin and RAS via Axin binding, effectively suppresses the stemness of CSCs as shown in CRC spheroids and small intestinal tumors of ApcMin/+/K-RasG12DLA2 mice. Moreover, KYA1797K also suppresses the stemness of cells in CRC patient avatar model systems, such as patient-derived tumor organoids (PDTOs) and patient-derived tumor xenograft (PDTX).

Conclusion

Our results suggest that destabilization of both β-catenin and RAS is a potential therapeutic strategy for controlling stemness of CRC cells.
Patient factors associated with waiting time to pediatric rheumatologist consultation for patients with juvenile idiopathic arthritis
Authors: Barber Claire E. H. , Barnabe Cheryl , Benseler Susanne , Chin Ricky , Johnson Nicole , Luca Nadia , Miettunen Paivi , Twilt Marinka , Veeramreddy Dwaraka , Shiff Natalie J. , Schmeling Heinrike
Published: March 2020

Background

Early diagnosis and treatment of Juvenile Idiopathic Arthritis (JIA) is essential to optimize outcomes. Wait times (WTs) to consultation with a pediatric rheumatologist consultation is a Canadian quality measure, with benchmarks set at 7 days for systemic JIA (sJIA) and 4 weeks for other JIA categories. In this study we assess WTs for JIA at a single academic center and describe factors associated with longer WTs.

Methods

This was a retrospective cohort study of 164 patients enrolled in a pharmacogenetic study in Alberta between 2002 and 2018. Limited chart reviews were conducted to evaluate dates of referral and first rheumatology visit to calculate WTs for receipt of pediatric rheumatology care. Cox proportional hazard models identified factors associated with WTs considering variables at the first pediatric rheumatology visit including: JIA category, age, sex, distance to the pediatric rheumatology clinic, number of active joints, pain and C-reactive protein.

Results

The median age at diagnosis was 8.0 years (interquartile range, IQR 3.5, 12.0) and 46% of patients had oligoarticular JIA. Only 18 patients (11%) were from rural locations. The median WT for all patients met the national benchmark (22 days, IQR, 9, 44) with no statistically significant difference between WTs among JIA categories (p = 0.055). Importantly, the majority of sJIA cases met the 7-day benchmark (67%) with a median WT of 1.5 days. Older age was associated with longer WT (HR 0.94, 95% CI 0.89, 0.98, p = 0.005).

Conclusion

Median benchmarks were met, however delays in older patients highlight the need for monitoring WTs.
Perturbation of gut microbiota decreases susceptibility but does not modulate ongoing autoimmune neurological disease
Authors: Gödel Clemens , Kunkel Birgit , Kashani Alireza , Lassmann Hans , Arumugam Manimozhiyan , Krishnamoorthy Gurumoorthy
Published: March 2020

The gut microbiota regulates the host immune and nervous systems and plays an important role in the pathogenesis of autoimmune neurological disease multiple sclerosis (MS). There are considerable efforts currently being undertaken to develop therapies for MS based on the modulation of microbiota. Evidence from experimental models suggests that the manipulation of microbiota through diet or antibiotics prior to the disease development limits disease susceptibility. However, it is currently unclear if microbiota manipulation therapies would also have an impact on ongoing neurological disease. Here, we examined the effect of antibiotic-based microbiota modulation in spontaneous experimental autoimmune encephalomyelitis (EAE) mouse models of MS before and after the onset of autoimmune disease. Prophylactic antibiotic treatment led to a significant reduction of susceptibility to spontaneous EAE. In contrast, antibiotic treatment after the onset of spontaneous EAE did not show a significant amelioration. These results reveal that the perturbation of gut bacteria alters disease susceptibility but has minimal impact on the ongoing neurological disease.
A double-blind, randomized controlled trial to explore oral tranexamic acid as adjunct for the treatment for postpartum hemorrhage
Authors: Diop Ayisha , Abbas Dina , Ngoc Nguyen thi Nhu , Martin Roxanne , Razafi Ange , Tuyet Hoang Thi Diem , Winikoff Beverly
Published: March 2020

Background

Oral tranexamic acid (TXA), if effective in reducing blood loss after delivery for women experiencing primary PPH, could be administered where parenteral administration is not feasible. This trial assessed the efficacy, safety, and acceptability of oral TXA when used as an adjunct to sublingual misoprostol to treat postpartum hemorrhage (PPH) following vaginal delivery.

Methods

From October 2016 to January 2018, women presenting at four hospitals in Senegal and Vietnam for vaginal delivery were screened for enrollment in the trial. Women diagnosed with postpartum hemorrhage (defined as blood loss ≥700 ml) were randomized to receive either oral TXA (1950 mg) or placebo in addition to 800 mcg sublingual misoprostol. Postpartum blood loss was measured using a calibrated drape. Blood loss for all PPH cases was recorded for 2 h after administration of the drugs. The primary outcome measure was the proportion of women with bleeding controlled with the trial regimen without recourse to further treatment. Secondary outcomes including the rate of severe PPH, mean/median blood loss, use of additional uterotonics and/or interventions side effects, and acceptability were also recorded.

Results

Of the 258 women who received treatment for PPH, 128 received placebo and misoprostol and 130 received TXA and misoprostol. The proportion of women who had active bleeding controlled with trial drugs alone and no additional interventions was similar in both groups: 77(60.2%) placebo; 74 (56.9%) TXA, p = 0.59). Use of other interventions to control bleeding, including uterotonics, did not differ significantly between groups. Median blood loss at PPH diagnosis was 700 ml in both groups. Uterine atony alone or in addition to another cause contributed to over 90% of PPH cases reported (92.2% placebo vs. 91.5% TXA), other causes included perineal and cervical lacerations and retained placenta. Reports of side effects and acceptability were similar in the two groups.

Conclusion

Adjunct use of oral TXA with misoprostol to treat PPH resulted in similar clinical and acceptability outcomes when compared to treatment with misoprostol alone.

Trial registration

This trial was registered with ClinicalTrials.gov, number NCT02805426. Registered on 3 September 2016.
Differential expression of human papillomavirus 16-, 18-, 52-, and 58-derived transcripts in cervical intraepithelial neoplasia
Authors: Baba Satoshi , Taguchi Ayumi , Kawata Akira , Hara Konan , Eguchi Satoko , Mori Mayuyo , Adachi Katsuyuki , Mori Seiichiro , Iwata Takashi , Mitsuhashi Akira , Maeda Daichi , Komatsu Atsushi , Nagamatsu Takeshi , Oda Katsutoshi , Kukimoto Iwao , Osuga Yutaka , Fujii Tomoyuki , Kawana Kei
Published: March 2020

Background

Human papillomavirus (HPV) infection is a primary cause of cervical cancer. Although epidemiologic study revealed that carcinogenic risk differs according to HPV genotypes, the expression patterns of HPV-derived transcripts and their dependence on HPV genotypes have not yet been fully elucidated.

Methods

In this study, 382 patients with abnormal cervical cytology were enrolled to assess the associations between HPV-derived transcripts and cervical intraepithelial neoplasia (CIN) grades and/or HPV genotypes. Specifically, four HPV-derived transcripts, namely, oncogenes E6 and E6*, E1^E4, and viral capsid protein L1 in four major HPV genotypes—HPV 16, 18, 52, and 58—were investigated.

Results

The detection rate of E6/E6* increased with CIN progression, whereas there was no significant change in the detection rate of E1^E4 or L1 among CIN grades. In addition, we found that L1 gene expression was HPV type-dependent. Almost all HPV 52-positive specimens, approximately 50% of HPV 58-positive specimens, around 33% of HPV 16-positive specimens, and only one HPV18-positive specimen expressed L1.

Conclusions

We demonstrated that HPV-derived transcripts are HPV genotype-dependent. Especially, expression patterns of L1 gene expression might reflect HPV genotype-dependent patterns of carcinogenesis.
Molecular karyotypes of loquat (Eriobotrya japonica) aneuploids can be detected by using SSR markers combined with quantitative PCR irrespective of heterozygosity
Authors: Wen Guo , Dang Jiangbo , Xie Zhongyi , Wang Jinying , Jiang Pengfei , Guo Qigao , Liang Guolu
Published: March 2020

Background

Aneuploidy, a condition caused by an imbalance between the relative dosages of chromosomes, generally produces a novel phenotype specific to the molecular karyotype. Few techniques are currently available for detecting the molecular karyotypes of aneuploids in plants.

Results

Based on this imbalance in chromosome dosage, a new approach (referred to as ‘SSR-qPCR’) combining simple sequence repeat (SSR) markers and quantitative real-time PCR (qPCR) has been developed and utilized to detect some common aneuploids irrespective of heterozygosity. We screened 17 specific SSR markers covering all loquat linkage groups and redesigned 6 pairs of primers for SSR markers that can detect loquat chromosome aneuploidies. The SSR-qPCR detection results obtained for hybrid progeny and open-pollination progeny of triploid loquat showed diagnostic accuracies of 88.9% and 62.5%, respectively, compared with the chromosome preparation results.

Conclusion

SSR-qPCR can detect loquat aneuploids and be used to construct the entire molecular karyotypes of aneuploid individuals. Therefore, this method offers a novel alternative for the detection of chromosome aneuploidies.
A qualitative study of design stakeholders’ views of developing and implementing a registry-based learning health system
Authors: Dixon-Woods Mary , Campbell Anne , Chang Trillium , Martin Graham , Georgiadis Alexandros , Heney Veronica , Chew Sarah , Van Citters Aricca , Sabadosa Kathryn A. , Nelson Eugene C.
Published: March 2020

Background

New opportunities to record, collate, and analyze routine patient data have prompted optimism about the potential of learning health systems. However, real-life examples of such systems remain rare and few have been exposed to study. We aimed to examine the views of design stakeholders on designing and implementing a US-based registry-enabled care and learning system for cystic fibrosis (RCLS-CF).

Methods

We conducted a two-phase qualitative study with stakeholders involved in designing, implementing, and using the RCLS-CF. First, we conducted semi-structured interviews with 19 program personnels involved in design and delivery of the program. We then undertook 11 follow-up interviews. Analysis of interviews was based on the constant comparative method, supported by NVivo software.

Results

The organizing principle for the RCLS-CF was a shift to more partnership-based relationships between patients and clinicians, founded in values of co-production, and facilitated by technology-enabled data sharing. Participants proposed that, for the system to be successful, the data it collects must be both clinically useful and meaningful to patients and clinicians. They suggested that the prerequisites included a technological infrastructure capable of supporting data entry and joint decision-making in an accessible way, and a set of social conditions, including willingness from patients and clinicians alike to work together in new ways that build on the expertise of both parties. Follow-up interviews highlighted some of the obstacles, including technical challenges and practical constraints on refiguring relationships between clinicians and patients.

Conclusions

The values and vision underlying the RCLS-CF were shared and clearly and consistently articulated by design stakeholders. The challenges to realization were often not at the level of principle, but were both practical and social in character. Lessons from this study may be useful to other systems looking to harness the power of “big data” registries, including patient-reported data, for care, research, and quality improvement.
Sickle cell disease induces resistance to cutaneous carcinogenesis
Authors: Soutou Boutros , Senet Patricia , Lionnet François , Habibi Anoosha , Aractingi Sélim
Published: March 2020

Background

While skin carcinomas are reported in chronic ulcers and in patients treated with hydroxyurea (HU) for myeloproliferative neoplasms, no skin carcinoma has been reported in patients with sickle cell disease (SCD), presenting chronic skin ulcers or treated with HU. The objective was to estimate the risk of cutaneous malignant transformation in SCD patients with prolonged leg ulcers or under HU therapy.

Results

In this cross-sectional study, the cohort consisted of 1543 patients. In the first series, 29 patients presented a total of 53 ulcers lasting more than two years. The median age was 35 ± 8.4 years old. The median duration for a single ulcer was 9.2 ± 7 years. None of the examined ulcers showed any suspicious area of malignant transformation. In the second series, 187 patients treated with HU for more than two years were identified. The median age was 31.3 ± 9.9 years old. The median duration of treatment with HU was 6 ± 3.2 years. No skin carcinoma or actinic keratosis was recorded.

Conclusions

This study showed that skin carcinogenesis did not occur in our series of SCD patients exposed to transforming events such as long term HU treatment or prolonged leg ulcers.
Sinomenine inhibits amyloid beta-induced astrocyte activation and protects neurons against indirect toxicity
Authors: Singh Deepali , Agrawal Apurva , Singal Chitra Mohinder Singh , Pandey Hriday Shanker , Seth Pankaj , Sharma Shiv Kumar
Published: March 2020

Amyloid beta is a major constituent of the plaques found in the brains of patients suffering from Alzheimer’s disease (AD). A growing body of research work suggests that neuroinflammation plays important roles in the development of AD. Thus, considerable efforts are directed towards identification of compounds that can reduce or inhibit neuroinflammation. Here, we show that sinomenine, a compound present in a Chinese medicinal plant, Sinomenium acutum, inhibits oligomeric amyloid beta-induced production of reactive oxygen species (ROS), nitric oxide (NO) and inflammation-related molecules from astrocytic cells. The conditioned medium from oligomeric amyloid beta-treated astrocytic cells induces cell death in the hippocampal neuronal cells. Importantly, sinomenine inhibits this cell death. In addition, this compound has inhibitory effects on the production of ROS, NO and inflammation-related factors from oligomeric amyloid-beta treated human astrocytes. Finally, the conditioned medium from oligomeric amyloid beta-treated human astrocytes induces cell death in the primary culture of human neurons, which is inhibited by sinomenine. Thus, sinomenine inhibits amyloid beta-induced production of toxic factors from astrocytes, and confers protection to hippocampal neuronal cells as well as human neurons against indirect toxicity. The results suggest that this compound could provide beneficial effects in AD and other neurodegenerative conditions by reducing inflammation and neuronal cell death.
Rescue under ongoing CPR from an upper floor: evaluation of three different evacuation routes and mechanical and manual chest compressions: a manikin trial
Authors: Drinhaus Hendrik , Nüsgen Sebastian , Adams Niels , Wetsch Wolfgang A. , Annecke Thorsten
Published: March 2020

Background

If transport under ongoing cardiopulmonary resuscitation (CPR) from an upper floor is indicated, the ideal CPR-method and evacuation route is unknown hitherto. We aimed to elaborate a strategy for evacuation of patients under ongoing CPR from an upper floor, comparing three different evacuation routes and manual and mechanical chest compressions.

Methods

A CPR-training manikin recording CPR-quality was placed on the fifth floor and was evacuated to an ambulance via lift, turntable ladder, or staircase. Chest compressions were performed manually or with a mechanical CPR-device. Efficiency endpoints were compression depth and frequency, sufficiency of chest release, compared with European Resuscitation Council (ERC) Guidelines, and duration of the evacuation. Adverse outcomes were disconnection/dislocation of devices and hazards/accidents to the personnel.

Results

For all evacuation routes, compression depth and frequency were significantly more compliant with ERC-guidelines under mechanical CPR. Manual CPR was associated with considerable deviations from correct compression depth and frequency. Chest release only slightly differed between groups. Evacuation via lift under mechanical CPR was fastest and evacuation via turntable ladder under manual CPR was slowest. No device disconnections or accidents occurred, but hazard to personnel was perceived during evacuation via ladder under manual CPR.

Conclusions

In this study, a mechanical CPR-device proved to deliver better CPR-quality during evacuation from an upper floor. If a lift accessible with a stretcher is available, this route should be preferred, regardless of manual or mechanical CPR. Turntable ladders can only be meaningfully used with mechanical CPR, otherwise CPR-quality is poor and hazard to the personnel is increased. Not all evacuation routes may be useable in a specific real-life scenario.

Trial registration

German Clinical Trials Registry, www.drks.de, registration number DRKS00012885, registration date 17.08.2017.
Designs for adding a treatment arm to an ongoing clinical trial
Authors: Bennett Maxine , Mander Adrian P.
Published: March 2020

Background

For many disease areas, there are often treatments in different stages of the development process. We consider the design of a two-arm parallel group trial where it is planned to add a new experimental treatment arm during the trial. This could potentially save money, patients, time and resources; however, the addition of a treatment arm creates a multiple comparison problem. Current practice in trials when a new treatment arm has been added is to compare the new treatment only to controls randomised concurrently, and this is the setting we consider here. Furthermore, for standard multi-arm trials, optimal allocation randomises a larger number of patients to the control arm than to each experimental treatment arm.

Methods

In this paper we propose an adaptive design, the aim of which is to adapt the sample size of the trial when the new treatment arm is added to control the family-wise error rate (FWER) in the strong sense, whilst maintaining the marginal power of each treatment-to-control comparison at the level of the original study. We explore optimal allocation for designs where a treatment arm is added with the aim of increasing the overall power of the study, where we define the overall power to be the probability of detecting all treatments that are better than the control.

Results and conclusions

An increase in sample size is required to maintain the marginal power for each pairwise comparison when adding a treatment arm if control of the FWER is required at the level of the type I error in the original study. When control of the FWER is required in a single trial which adds an additional experimental treatment arm, but control of the FWER is not required in separate trials, depending on the design characteristics, it may be better to run a separate trial for each experimental treatment, in terms of the number of patients required. An increase in overall power can be achieved when optimal allocation is used once a treatment arm has been added to the trial, rather than continuing with equal allocation to all treatment arms.
Patient experience of the informed consent process during acute myocardial infarction: a sub-study of the VALIDATE-SWEDEHEART trial
Authors: Olsson Anneli , Ring Camilla , Josefsson Johan , Eriksson Annika , Rylance Rebecca , Fröbert Ole , James Stefan , Sparv David , Erlinge David
Published: March 2020

Objective

We aimed to assess the patient experience of informed consent (IC) during acute myocardial infarction (AMI) in a sub-study of the VALIDATE-SWEDEHEART trial. The original trial compared two anticoagulant agents in patients undergoing coronary intervention. A witnessed oral IC was required prior to randomization in patients with ST-segment elevation myocardial infarction, which was subsequently complemented with a written IC after percutaneous coronary intervention. Written consent was obtained before angiography in patients with non-ST-segment elevation myocardial infarction.

Background

The IC process in patients with AMI is under debate. Earlier trials in this population have required prospective consent before randomization. A trial published some years ago used deferred consent, but the patient experience of this process is poorly studied.

Methods

A total of 414 patients who participated in the main trial were enrolled and asked the following questions: (1) Do you remember being asked to participate in a study? (2) How was your experience of being asked to participate; do you remember it being positive or negative? (3) Would you have liked more information about the study? (4) Do you think it would have been better if you were included in the study without being informed until a later time?

Results

Of these patients, 94% remembered being included; 85% of them experienced this positively, 12% were neutral and 3% negative. Regarding more information, 88% did not want further information, and 68% expressed that they wanted to be consulted before inclusion. Of the patients, 5% thought it would have been better to have study inclusion without consent, and 27% considered it of no importance.

Conclusion

It is reasonable to ask patients for verbal IC in the acute phase of AMI. Most patients felt positively about being asked to participate and had knowledge of being enrolled in a scientific study. In addition they objected to providing IC after randomization and treatment.

Trial registration

VALIDATE-SWEDEHEART European Union Clinical Trials Register: 2012-005260-10. ClinicalTrials.gov: NCT02311231. Registered on 8 Dec 2014.