bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimising the utility of pleural fluid adenosine deaminase for the diagnosis of tuberculous pleural effusion
Authors: Huan Nai-Chien , Khor Inn Shih , Ramarmuty Hema Yamini , Lim Ming Yao , Ng Kai Choon , Syaripuddin Alfieyanto , Lee Qin Zhi , Teo Wee Jing , Sivaraman Kannan Kunji Kannan 
Published: December 2020

Introduction: Pleural fluid adenosine deaminase (pfADA) is a simple, rapid and inexpensive surrogate marker for tuberculous pleural effusion (TPE). A nationwide cut-off of 40 U/L is currently used based on overseas data. There is a need to optimise the diagnostic utility of pfADA by establishing a local cut-off value. In this study, we aimed to describe the demographics and clinical characteristics of patients with TPE and non-TPE; determine the sensitivity and specificity of current pfADA of 40 U/L; and establish a new local pfADA cut-off for TPE. Methods: We conducted a single-centre, observational, prospective study of patients with exudative pleural effusion and pfADA measured from 1 October 2019 to 30 April 2020 at Queen Elizabeth Hospital, Malaysia. Results: The diagnosis of analysed patients ( n = 93) included TPE ( n = 41), malignancy ( n = 28), parapneumonic effusion ( n = 12) and other causes ( n = 12). The mean pfADA was 51.15 U/L (standard deviation (SD) = 13.77) among TPE group and 18.86 U/L (SD = 12.33) among non-TPE. When analysis was restricted to TPE patients, the local pfADA cut-off is 29.6 U/L, with a sensitivity of 97.6% and specificity of 90.4%. The current pfADA of 40 U/L has a sensitivity of 87.8% and specificity of 92.3%. Conclusion: We established a local pfADA cut-off of 29.6 U/L for TPE. Optimising the utility of pfADA helps to enhance clinicians’ treatment confidence of TPE when initial work-up is inconclusive.
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.
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.
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

Abstract
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

BackgroundCardiopulmonary 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.MethodsCPET 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.ResultsOver 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.ConclusionThe 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.