bluuebunny/crossref_metadata_2025 huggingface dataset:
Structured benefit–risk evaluation for medicinal products: review of quantitative benefit–risk assessment findings in the literature
Authors: Kürzinger Marie-Laure , Douarin Ludivine , Uzun Ievgeniia , El-Haddad Chantal , Hurst William , Juhaeri Juhaeri , Tcherny-Lessenot Stéphanie
Published: December 2020

A favorable benefit–risk profile remains an essential requirement for marketing authorization of medicinal drugs and devices. Furthermore, prior subjective, implicit and inconsistent ad hoc benefit–risk assessment methods have rightly evolved towards more systematic, explicit or “structured” approaches. Contemporary structured benefit–risk evaluation aims at providing an objective assessment of the benefit–risk profile of medicinal products and a higher transparency for decision making purposes. The use of a descriptive framework should be the preferred starting point for a structured benefit–risk assessment. In support of more precise assessments, quantitative and semi-quantitative methodologies have been developed and utilized to complement descriptive or qualitative frameworks in order to facilitate the structured evaluation of the benefit–risk profile of medicinal products. In addition, quantitative structured benefit–risk analysis allows integration of patient preference data. Collecting patient perspectives throughout the medical product development process has become increasingly important and key to the regulatory decision-making process. Both industry and regulatory authorities increasingly rely on descriptive structured benefit–risk evaluation and frameworks in drug, vaccine and device evaluation and comparison. Although varied qualitative methods are more commonplace, quantitative approaches have recently been emphasized. However, it is unclear how frequently these quantitative frameworks have been used by pharmaceutical companies to support submission dossiers for drug approvals or to respond to the health authorities’ requests. The objective of this study has been to identify and review, for the first time, currently available, published, structured, quantitative benefit–risk evaluations which may have informed health care professionals and/or payor as well as contributed to decision making purposes in the regulatory setting for drug, vaccine and/or device approval.

Plain language summary

Quantitative evaluation of the benefit–risk balance for medicinal products The review of the benefits and the risks associated with a medicinal product is called benefit–risk assessment. One of the conditions for a medicinal product to receive marketing authorization is to demonstrate a positive benefit–risk balance in which the benefits outweigh the risks. In order to enhance the transparency and consistency in the assessment of benefit–risk balance, frameworks and quantitative methods have been developed for decision making purposes and regulatory approvals of medicinal products. This article considers published quantitative benefit–risk evaluations which may have informed health care professionals and/or payor as well as contributed to decision making purposes in the regulatory setting for drug, vaccine and/or device approval.
Ending the pain of children with severe epilepsy? An audit of the impact of medical cannabis in 10 patients
Authors: Zafar RR , Schlag AK , Nutt DJ
Published: December 2020

Background

Scientific and anecdotal evidence suggest that whole plant cannabis extracts are effective in reducing seizure frequency in individuals with a range of epileptic etiologies. We report a case series of 10 individuals using CBMPs in the UK to treat their conditions.

Methods

In this retrospective study, we report on patients (aged 2-48) with severe, intractable, childhood onset epilepsies using combined cannabinoid therapy. Carers of patients provided details through the charity ‘End our Pain’ and these data were subsequently analysed. Our primary objective was to assess changes in monthly seizure frequency pre and post initiation of CBMPs. We also report on previous and current AED, CBD:THC daily dose, quality of life and financial costs associated with CBMP private prescription. Change in monthly seizure frequency were assessed using a Wilcoxon Signed-ranks test.

Results

Of the 10 patients enrolled in the study there was an 97% mean reduction in monthly seizure frequency post initiation of CBMPs which was statistically significant (Z = 0, p < 0·01). We showed a reduction in AED use following initiation of CBMPs from a mean of 8 (±5·98) to 1 (±1·05). All patients were using either Bedrolite or Bedica (Bedrocan International) as their CBMP. Individual daily doses of THC ranged from 6·6mg – 26·5mg and for CBD, 200 mg – 550 mg. Average monthly cost of CBMP was £1816·20.

Interpretation

Our findings suggest a combination of CBD and THC based products are effective in reducing seizure frequency in a range of epileptic conditions. We highlight the inefficacy of the healthcare system in supporting these patients who bare great personal and financial burdens. We encourage specialist physicians and relevant bodies to permit greater ease of access of these medications to those patients where efficacy has been shown.
Urology boot camp for medical students: improving knowledge and confidence in preparation for clinical practice
Authors: Ellis Ricky , Ellerington Clare , Henry Mei-Ling
Published: December 2020

Objectives:

Undergraduate exposure to urology is limited and junior doctors often feel underprepared for managing urological problems. We therefore established a one-day urology teaching course which covered the entire British Association of Urological Surgeons curriculum.

Methods:

Graduates of a teaching hospital undertook a survey regarding their practical skills and knowledge in urology ( n=20), with responses compared to a sample of students who attended the boot camp ( n=24).

Results:

Forty per cent of graduates thought they knew most of the curriculum and 0% knew the entire curriculum, increasing to 79.4% and 8.3%, respectively, in the post-boot camp cohort. Forty per cent felt ‘mostly prepared’ for final examinations, increasing to 70.8%; 35% rated their knowledge as ‘good’, increasing to 50%, with a further 12.5% feeling it was ‘excellent’; 0% were ‘very confident’ in examination skills, increasing to 20.8%. One hundred per cent of students thought the boot camp helped in preparation for medical finals, 70.8% felt it better prepared them for foundation training. All course candidates thought the course increased their knowledge and skills in urology.

Conclusion:

This urology boot camp improves medical students’ skills and knowledge. This course would benefit medical students nationally, providing comprehensive, standardised training in urology and preparing students for final examinations and foundation years.

Level of evidence:

Not applicable.
A Single-Center Retrospective Study on the Initiation of Peritoneal Dialysis in Patients With Cardiorenal Syndrome and Subsequent Hospitalizations
Authors: Auguste Bourne L. , Agarwal Arnav , Ibrahim Ali Z. , Girsberger Michael Y. , Abreu Zita , McQuillan Rory F. , Bargman Joanne M.
Published: December 2020

Background:

Inotropic dependence and diuretic resistance in patients with cardiorenal syndrome (CRS) lead to frequent hospitalizations and are associated with high mortality. Starting peritoneal dialysis (PD) acutely (within 2 weeks of a heart failure hospitalization) offers effective volume removal without hemodynamic compromise in this population. There is little data on this approach in the North American literature.

Objective:

To determine whether volume-overloaded patients with CRS on maximal doses of diuretic therapy had reduced hospitalization for heart failure following PD initiation.

Design:

Retrospective cohort study.

Setting:

Academic hospital network (University Health Network, Toronto, Ontario).

Patients:

Patients with CRS receiving a bedside catheter and starting PD within 2 weeks of insertion at the University Health Network from January 1, 2013, to December 31, 2018.

Methods and measurements:

Data for heart failure–related hospitalizations and length of stay 6 months before and after PD initiation were collected. Patients who died, switched to hemodialysis, or were transferred to another facility within 6 months of starting PD were excluded from the analysis.

Results:

We identified 31 patients with CRS who had a bedside PD catheter inserted. The average age of patients was 66.0 ± 13.0 years. There were 7 (22.6%) deaths and 4 (12.9%) transfers to other programs or hemodialysis within 6 months of catheter insertion. After exclusion, we analyzed hospitalization and length of stay data for 20 patients. The hospitalization rate 6 months before PD initiation was 6.9 admissions per 1000 patient-days. This decreased to 2.5 admissions per 1000 patient-days after PD initiation. In addition, there was also a significant reduction in the average length of stay per hospitalization (24.1-3.9 days; P = .001).

Limitations:

Our study did not assess the severity of heart failure symptoms using a standardized functional classification system. We did not assess quality of life and illness intrusiveness scores before and after starting dialysis, nor did we capture non–heart-failure-related hospitalizations or external admissions at other hospital sites. We limited eligibility to clinically stable patients with no prior major abdominal surgical history in a single Canadian PD program using bedside ultrasound approach for catheter insertions by experienced nephrologists and included a small number of patients.

Conclusions:

Volume-overloaded patients with CRS receiving maximal diuretic therapy have lower hospitalization rates and shorter stays after initiation of PD. The development of a bedside PD catheter insertion program and close collaboration between nephrology and cardiology services may facilitate acute start dialysis in this population.
SEMPRE Autumn 2020 Conference: The Role of Music Psychology Research in a Complex World
Authors: Kirby Melissa L.
Published: December 2020

Each year, the Society for Education, Music and Psychology Research (SEMPRE) hosts two conferences, covering a range of themes within music education and psychology research. The Autumn 2020 conference took place on September 9–11. The theme of the conference was ‘The role of music psychology research in a complex world: Implications, applications, and debates’; a particularly appropriate theme given the complex and challenging nature of 2020. Owing to the COVID-19 pandemic, this conference was hosted virtually by the University of Leeds. This report provides an overview of the conference, reflects on its key themes, and discusses the opportunities and challenges of online conferencing.
Willingness of Patients With Knee Osteoarthritis to Use Telemedicine Amid Sars-CoV-2 Outbreak
Authors: Takahashi Tsuneari , Ae Ryusuke , Minami Kensuke , Shibata Meiwa , Kubo Tatsuya , Kosami Koki , Takeshita Katsushi
Published: December 2020

Background:

There is no report yet on the application of telemedicine in orthopedic practice in Japan. With a focus on patients with KOA, we investigated the willingness of patients to use telemedicine by assessing factors such as the patient’s age, smartphone possession, hospital visiting time, and severity of KOA.

Methods:

Data of patients who regularly consulted orthopedic surgeons at our institutions from April 2020 to June 2020 were retrospectively analyzed using an electronic medical database. The patients were diagnosed with KOA according to clinical and radiological findings, according to the Kellgren-Lawrence (KL) classification. included were patients with KOA with KL classification above grade 2. All patients were asked: 1) whether they were willing to use telemedicine (Yes or No), 2) the reason why they answered Yes, 3) the reason why they answered No, 4) if they possessed a smartphone, 5) their numeric rating scale for pain at their last outpatient visit after the Sars-CoV-2 epidemic emerged, and 6) the time required for visiting hospital from their house. Patients were stratified into 2 groups depending on whether they answered Yes (Group Y) or No (group N). Comparisons between the groups concerning smartphone possession, NRS pain, hospital visiting times, and distribution of KL grade were made.

Results:

Only 36.7% of the patients with KOA said they were willing to use telemedicine. The average age of group Y was significantly younger than that of group N (67.9 ± 9.1 vs 73.1 ± 8.0, P = 0.0026) and the cutoff age was 70.0 years. In addition, the rate of smartphone possession was significantly higher in group Y than in group N (82.5% vs 34.5%, P < 0.001). Hospital visit times and the severity of KOA did not differ between the groups.

Conclusion:

Age is a barrier to the adoption of telemedicine.
COX-2 Overexpression in Schneiderian Papillomas
Authors: Suh Jeffrey D. , Hur Kevin , Ference Elisabeth H. , Lam David D. , Fong Andrew , Correa Adrian J. , Wrobel Bozena
Published: December 2020

Background

Schneiderian papillomas (SP) are aggressive sinonasal tumors that occasionally extend into areas that are surgically unresectable.

Objective

evaluate the signifcance of cyclo-oxygenase-2 (COX-2) expression in SP.

Methods

Immunohistochemistry for COX-2 was performed on SP samples and middle turbinates from chronic rhinosinusitis without nasal polyps controls obtained during surgical resection between 2009–2017. A positive stain was defined as having 10% or more cells exhibiting diffuse immunoreactivity. Comparisons were performed using Fisher Exact tests, t-tests, and ANOVA.

Results

The study included 67 tumor samples and 9 controls from two academic institutions. The mean age of the SP group was 55.4 years and 53.2 years in the control group (p = 0.71). Thirty-nine (58.2%) SP patients had previous surgery compared to 1 (11.1%) in the control group (p = 0.01). The most common tumor attachment sites were the maxillary (47.8%) and ethmoid (25.4%) sinuses. Fifteen (22.4%) SP samples stained strongly positive for COX-2 and 24 (35.8%) stained weakly positive compared to no positive stains in the control group (p < 0.01). When stratified by COX-2 intensity, there were no statistically significant differences in gender, smoking history, history of previous sinus surgery, site of attachment, papilloma subtype, or future recurrence between SP samples.

Conclusion

COX-2 was overexpressed in 58.2% of SP cases, and strongly positive in 22.4% of cases, compared to no positive staining among controls. No significant differences in COX-2 expression were observed between SP subtypes or recurrent tumors. Further studies are warranted to evaluate COX-2 as a possible therapeutic target in tumors that overexpress the enzyme.
Historical Burden or Lacking Effort? Caste Perceptions of Dalit Socio-economic Conditions
Authors: Swaminathan Siddharth
Published: December 2020

Why do some upper caste respondents view Dalit socio-economic conditions as a consequence of a lack of effort by Dalits, while others see it as a consequence of systematic discrimination and exclusion of Dalits from opportunities across generations? What explains this variation? This forms the central question I explore in this article. Two commonly held explanations for much of the observed upper caste behaviours towards Dalits also explain the divergent opinions held by upper caste respondents on the reasons for current Dalit socio-economic conditions. Using individual level data from the Politics and Society between Elections survey, I find that a negative bias toward Dalits that arises when upper caste respondents perceive themselves as more hardworking than Dalits and a perception of the relatively favourable treatment of Dalits by government officials significantly explain differences in upper caste opinions. Persistent inequalities reinforced by denying the historical burden borne by Dalits over centuries ultimately renders social change meaningless and democratic deepening a pipe dream.
Does Everyday Conversation Contribute to Cognitive Functioning? A Comparison of Brain Activity During Task-Oriented and Life-Worldly Communication Using Near-Infrared Spectroscopy
Authors: Fukaya Yasuko , Kawaguchi Minato , Kitamura Takanori
Published: December 2020

This study aimed to explore differences in frontal lobe brain activity associated with two types of communication: task-oriented and life-worldly, the latter of which largely overlaps with everyday conversation. Using near-infrared spectroscopy, we explored differences by comparing oxygenated hemoglobin concentrations associated with periods of rest and conversation in two experimental groups comprising older and younger adults. Artifacts were removed from the signals using discrete wavelet transforms. Paired t-tests were used to compare the resulting data for the two types. The results showed that oxygenated hemoglobin levels during life-worldly communication were significantly higher than at baseline or during task-oriented communication, particularly for the older adult group. In addition, during life-worldly communication, relatively high levels of brain activity were found in the upper part of the Broca area and in the premotor cortex. These results, which suggest that life-worldly communication generates more activity in the frontal lobe, could potentially contribute to improving how caregivers communicate with older patients/residents in hospitals and nursing homes.
Screening for Depression in Old Age With Very Short Instruments: The DIA-S4 Compared to the GDS5 and GDS4
Authors: Heidenblut Sonja , Zank Susanne
Published: December 2020

Purpose of the Study: This article presents a short form of the Depression in old Age Scale with four items (DIA-S4). The diagnostic accuracy of the DIA-S4 was tested and compared to short forms of the Geriatric Depression Scale (GDS5, GDS4). Methods: Using the Montgomery and Asberg Depression Rating Scale (MADRS) as gold standard, the scales were validated with a sample of N = 331 geriatric inpatients. Results: The DIA-S4 had an internal consistency of .70, the GDS5 of .55, and the GDS4 of .58. The test efficiency considering ROC analyses for the DIAS-4 was AUC = .86, for the GDS5 AUC = .78, and for the GDS4 AUC = .74. The best cut-off score for the DIA-S4 was 1.5 with a sensitivity of 87% and a specificity of 68%, for the GDS4 1.5 with a sensitivity of 58% and a specificity of 81%, and for the GDS5 1.5 with a sensitivity of 88% and a specificity of 49%. Conclusion: Based on the data of this study, the DIA-S4 shows better psychometrical qualities than the GDS5 and the GDS4. It can be used as a very short screening scale for depression in old age in research and clinical practice.
Development and Evaluation of Fishbone-Based Advanced Computational Thinking (FACT) Pedagogy: A Teacher-Student Collaborative Learning Environment in Engineering and Science Education
Authors: Gopinath B. , Santhi R.
Published: December 2020

In this article, Fishbone-based advanced computational thinking (FACT) pedagogy is proposed by fusing fishbone pedagogy and computational thinking pedagogy for enhancing teaching-learning process while teaching engineering and science courses, for engineering and science students respectively. The proposed FACT pedagogy has been implemented using the concept of X-ray machine in biomedical instrumentation course and biomolecules, in biochemistry course. Using fishbone approach, various components of X-ray machine in biomedical course and the components of biomolecules in biochemistry course are visually explained as ribs and riblets of a fishbone diagram, without coining the keywords X-ray and biomolecules in an engineering institution and science institution respectively. Finally, the targeted concept is arrived and explained. Similarly, the same concepts of X-ray and biomolecules are coined among students and they are asked to divide or decompose the concepts into sub-concepts separately. To implement and evaluate the proposed pedagogy, an engineering institution and a science institution have been selected and evaluation results have been published in this article. In this pedagogical approach, the same complex concept is taught as a backward thinking by the teacher using fishbone pedagogy and forward thinking by the students using computational thinking pedagogy. This combined approach helps students to understand any complex concept in science courses. Also, it helps the teachers to easily convey and embed the same among the student community while teaching science courses.
Dentists’ Perspectives on Commercial Practices in Private Dentistry
Authors: Holden A.C.L. , Adam L. , Thomson W.M.
Published: December 2020

Background:

Dentistry is predominantly provided in a commercial context in Australia. Despite this, little is known about how dentists navigate potential tensions that may arise between commercial and professional obligations in private dental practice. This analysis uses a qualitative approach to explore dentists’ perceptions and attitudes toward the commercialized nature of private dental practice and how these affect their professional role in providing care.

Methods:

Participants were recruited by advertising on social media, as well as through a professional association and a corporate dental group’s graduate training program. Data were collected from participants through interviews and written reflections. The data were subjected to thematic analysis to reveal deeper meanings and linkages between different emergent themes.

Results:

Twenty dentists who worked in private practice environments were recruited to take part. The analysis revealed the following themes within the data: dentistry devalued, commercial influences on professional behavior, the effect of advertising and competition on dentistry, ethical selling, and the impacts of commercialism on consumers of dentistry.

Conclusions:

Consumers of dentistry may only be superficially empowered by the commercialized context of private dental practice. Empowerment to decide which services to access and from whom does not address the inherent disparities that exist within the dentist-patient clinical relationship. Advertising and the active “selling” of oral health services are all designed to create dental consumers, not to empower them. While advertising might assist patients to understand available treatments, the primary objective of marketing is not health education. Increasing competition and consumer choice within dentistry may help to empower consumers of dental services but only if the dentist-patient relationship remains founded in altruistic intent, with the doctrine of “caveat emptor” (buyer beware) having no place within dentistry.

Knowledge Transfer Statement:

This research provides novel insights into how dentists experience the commercial context of private dental practice and how this is perceived to be both beneficial and detrimental to the consumers of dental services. This work will help to guide policy development to address the commercial determinants of oral health generated by the nature of commercialized dental practice environments.
A History of Anti-VEGF Inhibitors in the Ophthalmic Literature: A Bibliographic Review
Authors: Whitescarver Todd D. , Hobbs Samuel D. , Wade Christian I. , Winegar Jordan W. , Colyer Marcus H. , Reddy Ashvini K. , Drayna Paul M. , Justin Grant A.
Published: December 2020

Purpose:

This work aimed to analyze the 100 most-cited articles on antivascular endothelial growth factor (anti-VEGF) inhibitors.

Methods:

A literature search for anti-VEGF inhibitors using the Web of Science was completed using the bibliographic databases for peer-reviewed literature published in Ophthalmology, the New England Journal of Medicine, Journal of the American Medical Association, and Lancet. Primary outcomes were the most frequently cited articles and journals with the most citations as well as the specific drug and disease process studied.

Results:

There were 42 696 cumulative citations among the top 100 articles. The articles were published between 2004 to 2016, with most articles published in 2006. Ophthalmology published the greatest number of articles among the top 100 at 48, whereas the New England Journal of Medicine has the most citations per publication at 1714. Ranibizumab was the medication researched in most articles at 56, followed by bevacizumab at 48, aflibercept at 10, and pegaptanib at 9. Forty-two articles investigated treatment of age-related macular degeneration, followed by 24 investigating diabetic macular edema, 10 for retinal vein occlusion, 8 for proliferative diabetic retinopathy, 2 for retinopathy of prematurity and polypoidal choroidal vasculopathy, and 1 for corneal neovascularization.

Conclusions:

As evidenced by the considerable number of citations accumulated over the past 20 years, anti-VEGF inhibitors have led to significant research in ophthalmology.
Cost effectiveness of caplacizumab in acquired thrombotic thrombocytopenic purpura
Authors: Goshua George , Sinha Pranay , Hendrickson Jeanne E. , Tormey Christopher , Bendapudi Pavan K. , Lee Alfred Ian
Published: December 2020

Acquired thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease characterized by thrombotic microangiopathy leading to end-organ damage. The standard of care (SOC) treatment is therapeutic plasma exchange (TPE) alongside immunomodulation with steroids, with increasing use of rituximab ± other immunomodulatory agents. The addition of caplacizumab, a nanobody targeting von Willebrand factor, was shown to accelerate platelet count recovery and reduce TPE treatments and hospital length of stay in TTP patients treated in 2 major randomized clinical trials. The addition of caplacizumab to SOC also led to increased bleeding from transient reductions in von Willebrand factor and increased relapse rates. Using data from the 2 clinical trials of caplacizumab, we performed the first-ever cost-effectiveness analysis in TTP. Over a 5-year period, the projected incremental cost-effectiveness ratio (ICER) in our Markov model was $1 482 260, significantly above the accepted 2019 US willingness-to-pay threshold of $195 300. One-way sensitivity analyses showed the utility of the well state and the cost of caplacizumab to have the largest effects on ICER, with a reduction in caplacizumab cost demonstrating the single greatest impact on lowering the ICER. In a probabilistic sensitivity analysis, SOC was favored over caplacizumab in 100% of 10 000 iterations. Our data indicate that the addition of caplacizumab to SOC in treatment of acquired TTP is not cost effective because of the high cost of the medication and its failure to improve relapse rates. The potential impact of caplacizumab on health system cost using longer term follow-up data merits further study.
A 10-year follow-up of key gas exchange exercise parameters in a general population: results of the Study of Health in Pomerania
Authors: Stubbe Beate , Ittermann Till , Kaczmarek Sabine , Obst Anne , Bahls Martin , Bollmann Tom , Gläser Sven , Völzke Henry , Dörr Marcus , Ewert Ralf
Published: December 2020

Background

Cardiopulmonary exercise testing (CPET) is a frequently used method for the evaluation of the cardiorespiratory system. The prognostic relevance of the measured parameters is commonly known. Longitudinal data on cardiorespiratory fitness in a large sample of well-characterised healthy volunteers are rare in the literature.

Methods

CPET data of 615 healthy individuals who voluntarily took part in the Study of Health in Pomerania (SHIP) at three different measurement times were analysed. The median observation time was 10.5 years. The age range was 25–85 years.

Results

Over the observed timeframe and with increasing age, a decline in maximum power, peak oxygen uptake (V′O2peak) and oxygen uptake at anaerobic threshold (V′O2@AT) was detectable. This decline was aggravated with increasing age. For the minute ventilation (V′E)/carbon dioxide production (V′CO2) slope, an increase was measured in individuals aged ≥50 years only.

Conclusion

The present study affirms the decrease in aerobic capacity with increasing age in a selected, well-characterised, healthy study sample, which seems to be less pronounced in females.
Development and validation of an open-source, disposable, 3D-printed
in vitro
environmental exposure system for Transwell culture inserts
Authors: Chandiramohan Abiram , Dabaghi Mohammedhossein , Aguiar Jennifer A. , Tiessen Nicholas , Stewart Mary , Cao Quynh T. , Nguyen Jenny P. , Makhdami Nima , Cox Gerard , Doxey Andrew C. , Hirota Jeremy A.
Published: December 2020

Accessible
in vitro
models recapitulating the human airway that are amenable to study whole cannabis smoke exposure are needed for immunological and toxicological studies that inform public health policy and recreational cannabis use. In the present study, we developed and validated a novel three-dimensional (3D)-printed
in vitro
exposure system (IVES) that can be directly applied to study the effect of cannabis smoke exposure on primary human bronchial epithelial cells.

Using commercially available design software and a 3D printer, we designed a four-chamber Transwell insert holder for exposures to whole smoke. COMSOL Multiphysics software was used to model gas distribution, concentration gradients, velocity profile and shear stress within IVES. Following simulations, primary human bronchial epithelial cells cultured at the air�liquid interface on Transwell inserts were exposed to whole cannabis smoke using a modified version of the Foltin puff procedure. Following 24 h, outcome measurements included cell morphology, epithelial barrier function, lactate dehydrogenase (LDH) levels, cytokine expression and gene expression.

Whole smoke delivered through IVES possesses velocity profiles consistent with uniform gas distribution across the four chambers and complete mixing. Airflow velocity ranged between 1.0 and 1.5 �m�s
-1
and generated low shear stresses (<<1 Pa). Human airway epithelial cells exposed to cannabis smoke using IVES showed changes in cell morphology and disruption of barrier function without significant cytotoxicity. Cannabis smoke elevated interleukin-1 family cytokines and elevated CYP1A1 and CYP1B1 expression relative to control, validating IVES smoke exposure impacts in human airway epithelial cells at a molecular level.

The growing legalisation of cannabis on a global scale must be paired with research related to potential health impacts of lung exposures. IVES represents an accessible, open-source, exposure system that can be used to model varying types of cannabis smoke exposures with human airway epithelial cells grown under air�liquid interface culture conditions.
Pleuroparenchymal fibroelastosis inMycobacterium aviumcomplex pulmonary disease: clinical characteristics and prognostic impact
Authors: Yamamoto Yuji , Tsujino Kazuyuki , Kuge Tomoki , Okabe Fukuko , Kawasaki Takahiro , Matsuki Takanori , Kagawa Hiroyuki , Miki Mari , Miki Keisuke , Mori Masahide , Kida Hiroshi
Published: December 2020

The association betweenMycobacterium aviumcomplex pulmonary disease (MAC-PD) and pleuroparenchymal fibroelastosis (PPFE) has been reported previously, and interstitial pneumonia as a comorbidity is associated with a worse prognosis. However, no study has thoroughly reported on PPFE associated with MAC-PD. The present study investigated the prevalence, clinical characteristics, and prognostic impact of PPFE in patients with MAC-PD.

A total of 224 patients, newly diagnosed with MAC-PD, were retrospectively reviewed. At the time of diagnosis, chest high-resolution computed tomography (HRCT), sputum examination, and clinical characteristics were collected. The extent of PPFE and MAC-PD was evaluated semi-quantitatively using HRCT scores. Risk factor analysis for clinical or radiological deterioration necessitating multidrug antimicrobial treatment within 3 years, and all-cause mortality within 5 years, from the initial diagnosis was performed based on the PPFE score.

PPFE was observed in 59 out of 224 patients (26.3%). A higher PPFE score was a risk factor for dyspnoea, fatigue, and lower body mass index (BMI) (p<0.05). Although PPFE score did not correlate with clinical or radiological deterioration within 3 years (p=0.576), a higher PPFE score (adjusted OR 1.66, 95% CI 1.06–2.60, p=0.028) and lower BMI (adjusted OR 0.61, 95% CI 0.39–0.94, p=0.028) increased the risk of 5-year mortality.

PPFE is a relatively common complication and an independent poor prognostic factor of MAC-PD. This study highlights the need for further studies investigating whether the presence of PPFE can be a clinical indicator for initiating treatment of MAC-PD.
Association between high psychological distress and poor oral health-related quality of life (OHQoL) in Japanese community-dwelling people: the Nagasaki Islands Study
Authors: Sekiguchi Ai , Kawashiri Shin-ya , Hayashida Hideaki , Nagaura Yuki , Nobusue Kenichi , Nonaka Fumiaki , Yamanashi Hirotomo , Kitamura Masayasu , Kawasaki Koji , Fukuda Hideki , Iwasaki Takahiro , Saito Toshiyuki , Maeda Takahiro
Published: December 2020

Background

We investigated the association between psychological distress and oral health status/oral health-related quality of life (OHQoL) in Japanese community-dwelling people.

Methods

We conducted a cross-sectional study using data from the Nagasaki Islands Study. A total of 1183 (455 men and 728 women) has been analyzed in this study. Psychological distress was measured using the Kessler Psychological Distress Scale (K6). Oral health status was measured by dental examination. The OHQoL was measured using the General Oral Health Assessment Index (GOHAI). We defined the total score of ≥5 points on the K6 as high psychological distress (high-K6 group).

Results

The multiple linear regression analysis to identify the GOHAI showed that gender, K6, the total number of teeth, the number of dental caries, and visiting a dental clinic within the past 6 months significantly associated with the GOHAI. Among all of these variables, high-K6 (≥ 5) was a substantial contributing factor of the GOHAI (β = − 0.23, 95% Cl − 2.31 to −1.41, p < 0.0001).

Conclusions

It is likely that the individual with high psychological distress was strongly related to poor OHQoL even in the general population.
PyClone-VI: scalable inference of clonal population structures using whole genome data
Authors: Gillis Sierra , Roth Andrew
Published: December 2020

Background

At diagnosis tumours are typically composed of a mixture of genomically distinct malignant cell populations. Bulk sequencing of tumour samples coupled with computational deconvolution can be used to identify these populations and study cancer evolution. Existing computational methods for populations deconvolution are slow and/or potentially inaccurate when applied to large datasets generated by whole genome sequencing data.

Results

We describe PyClone-VI, a computationally efficient Bayesian statistical method for inferring the clonal population structure of cancers. We demonstrate the utility of the method by analyzing data from 1717 patients from PCAWG study and 100 patients from the TRACERx study.

Conclusions

Our proposed method is 10–100× times faster than existing methods, while providing results which are as accurate. Software implementing our method is freely availablehttps://github.com/Roth-Lab/pyclone-vi.
Predictors of acute cardiovascular events following acute exacerbation period for patients with COPD: a nested case–control study
Authors: Hu Wei-ping , Lhamo Tsokyi , Zhang Feng-ying , Hang Jing-qing , Zuo Yi-hui , Hua Jian-lan , Li Shan-qun , Zhang Jing
Published: December 2020

Background

It has been noted that there is an increase in the incidence of acute cardiovascular events (CVEs) in patients with chronic obstructive pulmonary disease (COPD) during an acute exacerbation (AE), thereby causing increased inpatient mortality. Thus, we have tried to identify predictors of acute CVEs in patients with AECOPD via a nested case–control study.

Methods

A total of 496 cases hospitalized for AECOPD were included in this study, and followed-up for up to 6 months after discharge. Acute CVEs in the AE period were defined as a new or worsening acute coronary syndrome (ACS), arrhythmia, or left ventricular disfunction (LVD). Predictors of CVEs were selected from several variables, including baseline characteristics and treatments in the stable period as well as symptoms, laboratory tests, complications and treatments in the AE period.

Results

Thirty cases (6.05%) had acute CVEs, namely 2 had ACS, 13 had LVD and 19 experienced some form of arrhythmia. Four deaths were observed in the CVE group, with significantly increased death risk compared with the non-CVE group (P = 0.001, OR = 5.81). Moreover, patients who had CVEs were more prone to have re-exacerbation within 3 months. Multivariate analysis showed that previous LVD history (P = 0.004, OR = 5.06), 20% increase in heart rate (HR) (P = 0.003, OR = 10.19), electrolyte disturbance (P = 0.01, OR = 4.24) and diuretics (P = 0.002, OR = 6.37) were independent predictors of CVEs. In addition, usage of theophylline, fluoroquinolone and inhaled beta agonists in the AE period were not statistically associated with acute CVEs.

Conclusions

Our preliminary study indicates that patients hospitalized for AECOPD with previous LVD history or increased HR need close observation and diuretics should be cautiously used with regular electrolyte monitoring. These findings need to be confirmed in a large cohort.
Short-term use of “ECMELLA” in the context of fulminant eosinophilic myocarditis with cardiogenic shock
Authors: Bohné Mintje , Chung Da-Un , Tigges Eike , van der Schalk Hendrick , Waddell Daniela , Schenker Niklas , Willems Stephan , Klingel Karin , Kivelitz Dietmar , Bahlmann Edda
Published: December 2020

Background

Eosinophilic myocarditis (EM) is a rare form of myocarditis. Clinical presentation is various, includes cardiogenic shock and can often be fatal. Diagnosis is based on myocardial eosinophilic infiltration in endomyocardial biopsy. Mechanical circulatory support (MCS) is often required in patients suffering from severe cardiogenic shock. Among the available MCS options the “ECMELLA” concept, a combination of left ventricular venting by Impella® device and extracorporeal life support (ECLS) is possibly able to provide the necessary time frame for diagnostics and initiation of anti-inflammatory medication in patients with fulminant myocarditis.

Case presentation

We report a case of a 38‐year‐old woman who was presented to us in severe cardiogenic shock, quickly requiring hemodynamic support by an Impella CP® device. Further dramatic hemodynamic deterioration accompanied by multi-organ dysfunction required escalation of MCS via ECLS as veno‐arterial extracorporeal membrane oxygenation (VA-ECMO). After histopathological diagnosis of EM, our patient was put on immunosuppressive therapy with prednisolone. Recovery of both right and left ventricular function allowed explanation of VA-ECMO on day 4 and further hemodynamic improvement allowed removal of the Impella® device on day 9. The patient was discharged after 7 weeks with fully restored cardiac function and in a good neurological state.

Conclusions

In severe cardiac shock due to fulminant EM the ECMELLA concept as bridge-to-recovery seems to be a valid option to provide the required time for diagnostics and specific therapy.
Integrating expert opinions with clinical trial data to analyse low-powered subgroup analyses: a Bayesian analysis of the VeRDiCT trial
Authors: Thirard Russell , Ascione Raimondo , Blazeby Jane M. , Rogers Chris A.
Published: December 2020

Background

Typically, subgroup analyses in clinical trials are conducted by comparing the intervention effect in each subgroup by means of an interaction test. However, trials are rarely, if ever, adequately powered for interaction tests, so clinically important interactions may go undetected. We discuss the application of Bayesian methods by using expert opinions alongside the trial data. We applied this methodology to the VeRDiCT trial investigating the effect of preoperative volume replacement therapy (VRT) versus no VRT (usual care) in diabetic patients undergoing cardiac surgery. Two subgroup effects were of clinical interest, a) preoperative renal failure and b) preoperative type of antidiabetic medication.

Methods

Clinical experts were identified within the VeRDiCT trial centre in the UK. A questionnaire was designed to elicit opinions on the impact of VRT on the primary outcome of time from surgery until medically fit for hospital discharge, in the different subgroups. Prior beliefs of the subgroup effect of VRT were elicited face-to-face using two unconditional and one conditional questions per subgroup analysis. The robustness of results to the ‘community of priors’ was assessed. The community of priors was built using the expert priors for the mean average treatment effect, the interaction effect or both in a Bayesian Cox proportional hazards model implemented in the STAN software in R.

Results

Expert opinions were obtained from 7 clinicians (6 cardiac surgeons and 1 cardiac anaesthetist). Participating experts believed VRT could reduce the length of recovery compared to usual care and the greatest benefit was expected in the subgroups with the more severe comorbidity. The Bayesian posterior estimates were more precise compared to the frequentist maximum likelihood estimate and were shifted toward the overall mean treatment effect.

Conclusions

In the VeRDiCT trial, the Bayesian analysis did not provide evidence of a difference in treatment effect across subgroups. However, this approach increased the precision of the estimated subgroup effects and produced more stable treatment effect point estimates than the frequentist approach. Trial methodologists are encouraged to prospectively consider Bayesian subgroup analyses when low-powered interaction tests are planned.

Trial registration

ISRCTN,ISRCTN02159606. Registered 29th October 2008.
Linkage of primary care prescribing records and pharmacy dispensing Records in the Salford Lung Study: application in asthma
Authors:   The Salford Lung Study Team, Tibble Holly , Lay-Flurrie James , Sheikh Aziz , Horne Rob , Mizani Mehrdad A. , Tsanas Athanasios
Published: December 2020

Background

Records of medication prescriptions can be used in conjunction with pharmacy dispensing records to investigate the incidence of adherence, which is defined as observing the treatment plans agreed between a patient and their clinician. Using prescribing records alone fails to identify primary non-adherence; medications not being collected from the dispensary. Using dispensing records alone means that cases of conditions that resolve and/or treatments that are discontinued will be unaccounted for. While using a linked prescribing and dispensing dataset to measure medication non-adherence is optimal, this linkage is not routinely conducted. Furthermore, without a unique common event identifier, linkage between these two datasets is not straightforward.

Methods

We undertook a secondary analysis of the Salford Lung Study dataset. A novel probabilistic record linkage methodology was developed matching asthma medication pharmacy dispensing records and primary care prescribing records, using semantic (meaning) and syntactic (structure) harmonization, domain knowledge integration, and natural language feature extraction. Cox survival analysis was conducted to assess factors associated with the time to medication dispensing after the prescription was written. Finally, we used a simplified record linkage algorithm in which only identical records were matched, for a naïve benchmarking to compare against the results of our proposed methodology.

Results

We matched 83% of pharmacy dispensing records to primary care prescribing records. Missing data were prevalent in the dispensing records which were not matched – approximately 60% for both medication strength and quantity. A naïve benchmarking approach, requiring perfect matching, identified one-quarter as many matching prescribing records as our methodology. Factors associated with delay (or failure) to collect the prescribed medication from a pharmacy included season, quantity of medication prescribed, previous dispensing history and class of medication. Our findings indicate that over 30% of prescriptions issued were not collected from a dispensary (primary non-adherence).

Conclusions

We have developed a probabilistic record linkage methodology matching a large percentage of pharmacy dispensing records with primary care prescribing records for asthma medications. This will allow researchers to link datasets in order to extract information about asthma medication non-adherence.
Experiences of managerial accountability in Ethiopia’s primary healthcare system: a qualitative study
Authors: Fetene Netsanet , Patel Akshar , Benyam Tibebu , Ayde Assefa , Desai Mayur M. , Curry Leslie , Linnander Erika
Published: December 2020

Background

Despite calls for improved accountability in global health systems, and a set of clear and consistent theoretical accountability frameworks, empirical descriptions of how accountability is experienced and enacted in low- and middle- income country (LMIC) settings is limited. Therefore, we sought to characterize how managers at all levels of Ethiopia’s primary healthcare system experience accountability in their daily practice.

Methods

We conducted in-depth key informant interviews with 41 key stakeholders across 4 regions (Amhara, Oromia, Southern Nations Nationalities and Peoples, and Tigray) in the context of the Primary Healthcare Transformation Initiative (PTI). Consistent with the principles of grounded theory, our team used the constant comparative method to identify emergent themes related to concrete areas that could be targeted to allow an overall culture of accountability to flourish.

Results

Emergent themes were: development of a shared understanding of system-wide accountability, streamlining of managerial reporting lines, strengthening of medico-legal knowledge and systems, and development of mechanisms for bottom-up accountability.

Conclusions

Findings may be valuable to policymakers seeking to create more effective national accountability frameworks; practitioners and development partners seeking to strengthen implementation of evidence-based accountability systems and practices; and researchers aiming to develop meaningful, practical measures of accountability in public health.
Monozygotic dichorionic-diamniotic pregnancies following single frozen-thawed blastocyst transfer: a retrospective case series
Authors: Li He , Shen Tingting , Sun Xiaoxi
Published: December 2020

Background

The primary aim of the study is to report cases of monozygotic dichorionic-diamniotic (DC-DA) pregnancies after single frozen-thawed blastocyst transfer.

Methods

This is a retrospective case series. All single frozen-thawed blastocyst transfer cycles performed between June 2013 and December 2018 at the Shanghai Ji Ai Genetics and IVF Institute, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China, were reviewed retrospectively. We included frozen embryo transfer (FET) cycles which clinical pregnancy was confirmed with multiple gestational sacs showed on ultrasonography at around 6 to 7 weeks of gestation. We then conducted an in-depth analysis to further exclude cases which contained newborns of different genders or natural FET cycles.

Results

Five thousand four hundred fifteen frozen-thawed single blastocyst transfer cycles were preformed between June 2013 and December 2018 at the Shanghai Ji Ai Genetics and IVF Institute, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China. Of these, fourteen women underwent a single blastocyst transfer and then achieved clinical pregnancy with an ultrasound diagnosis of multi-chorionic pregnancy. With one natural cycle FET excluded, we finally included thirteen single blastocyst transfer cycles performed in down-regulated controlled FET or hormone replacement FET, in which the possibility of concurrently spontaneous pregnancy was extremely small. These included 13 cases reveal the phenomenon of monozygotic DC-DA twinning after single blastocyst transfer, which challenges the classical theory that only monochorionic pregnancy could happen after 3 days of fertilization.

Conclusion

This case series suggest that single blastocyst transfer could result DC-DA pregnancies during IVF treatment.