bluuebunny/crossref_metadata_2025 huggingface dataset:
Bibliometric Analysis of Early COVID-19 Research: The Top 50 Cited Papers
Authors: ElHawary Hassan , Salimi Ali , Diab Nermin , Smith Lee
Published: October 2020

Introduction:

The COVID-19 pandemic is rapidly evolving with the number of cases exponentially rising. The research scientific community has reacted promptly as evidenced by an outstanding number of COVID-19 related publications. As the number of scientific publications rapidly rises, there is a need to dissect the factors that lead to highly impactful publications. To that end, the present paper summarizes the characteristics of the top 50 cited COVID-19-related publications that emerged early during the pandemic.

Methods:

A systematic search of the Web of Science, Scopus, and Google Scholar was performed, using keywords related to COVID-19 and SARS-CoV-19. Two independent authors reviewed all the search results, screening for the top 50 cited COVID-19-related articles. Inclusion criteria comprised any publication on COVID-19 or the SARS-CoV-2 virus. Data extracted included the type of study, journal, number of citations, number of authors, country of publication, and study content.

Results:

As of May 29th, the top 50 cited articles were cited 63849 times during the last 4 months. On average, 14 authors contributed to each publication. Over half of the identified articles were published in only 3 journals. Furthermore, 42% and 26% of the identified articles were retrospective case series and correspondence/viewpoints, respectively, while only 1 article was a randomized controlled trial. In terms of content, almost half (48%) of the identified publications reported clinical/radiological findings while only 7 out of the 50 articles investigated potential treatments.

Conclusion:

By highlighting the characteristics of the top 50 cited COVID-19-related articles, the authors hope to disseminate information that could assist researchers to identify the important topics, study characteristics, and gaps in the literature.
Focus on neglected features of cognitive rehabilitation in MS: Setting and mode of the treatment
Authors: Podda Jessica , Tacchino Andrea , Pedullà Ludovico , Monti Bragadin Margherita , Battaglia Mario Alberto , Brichetto Giampaolo
Published: October 2020

Cognitive rehabilitation in multiple sclerosis (MS) aims at reducing patients’ cognitive impairments, improving their awareness and ability to take cognitive difficulties into account in their daily living. However, at this moment, more high-quality randomized trials are needed to draw conclusion about the effectiveness of cognitive interventions in MS. Although existing studies provide clear descriptions of intervention key ingredients (e.g. targeted cognitive domain as well as treatment frequency and duration) and the practical details needed to manage these key elements (e.g. restorative approaches, compensatory strategies, or environmental modifications), other crucial aspects received less attention in rehabilitation research. The aim of this topical review is to try to elucidate some critical issues that were only partly addressed and analyzed by the scientific literature: setting (center-based vs home-based) and mode (individual vs group) of the cognitive rehabilitation treatment.
Outdoor transportation of influenza virus under natural wind field
Authors: Liu Wei , Zhang Chen , Li Yaning
Published: October 2020

The transportation of influenza virus in a group of buildings under the condition of natural wind field was studied. The curves of natural wind power spectrum and the velocity field with respect to time were simulated by the improved weighted amplitude wave superposition with fast Fourier transform. According to Davenport spectrum, the approximation function of wind velocity field with respect to time was used to simplify the calculation efforts. The average wind field and natural wind field were adopted to simulate the microbial contamination diffusion in a group of buildings. In the case of natural wind, the virus particles are dispersed faster from buildings, and the contamination concentration is low. However, the large downwind area may face the threat of virus contamination.
Place marketing, evolutionary theories and the management of multifaceted destinations: Cartagena, Colombia, as a study case
Authors: Bassols Narcís , Leicht Thomas
Published: October 2020

Tourist destinations generally offer a variety of attractions that local authorities or destination management organizations (DMOs) may incorporate into their promotional activities. This diversity of available assets has different stakeholder groups having to decide what the destination actually stands for. The present study connects existing frameworks about evolutionary dynamics and place marketing and applies them to multifaceted destinations to provide fresh insights into how these can be managed. It extends the discussion by taking the city of Cartagena de Indias, Colombia, as an in-depth case study to illustrate how multiple assets as well as multiple place identities can impact the management of a given destination. The main data source consisted of semi-structured interviews which were used to explore the (typologies of) attractions that best represent the destination and how these should be promoted according to the local institutional stakeholders. The results show that being a multifaceted destination poses significant challenges to the definition of tourism marketing strategies, even if most stakeholders agree that a shift from the traditional, beach-related elements towards more (intangible) cultural resources is necessary. The paper concludes by drawing some theoretical implications as well as practical recommendations for multiple asset destinations.
Visualization of diesel spray and combustion from lateral side of two-dimensional piston cavity in rapid compression and expansion machine
Authors: Fan Chengyuan , Wang Daoyuan , Nishida Keiya , Ogata Yoichi
Published: October 2020

Effect of spray/wall interaction in a rapid compression and expansion machine on mixture formation, ignition location, and soot generation was investigated. A two-dimensional piston cavity designed as the cross section of a reentrant piston was utilized to observe the spray and combustion process from the lateral side. The experiment was conducted at 120 MPa injection pressure under single and split injection strategies with an ambient gas of 15% O2 concentration. A shadow methodology was applied to investigate the interaction between the fuel spray and the piston cavity. Combined with the natural flame luminosity captured by a high-speed color video camera, the behaviors of the impinging spray and the combustion process were studied. The combustion characteristics of the in-cylinder pressure, heat release and combustion phase were recorded and analyzed simultaneously. The results showed that the split injection strategies effectively softened the heat release trace and promoted the onset of the main combustion. The cool-flame phenomenon was captured by using the high-speed color video camera, and the intense ignition was observed when the pilot spray was controlled to impinge on the lower lip of the piston rim. Moreover, results also showed that further extending the mixing process of the pilot spray is inclined to form a homogeneous mixture which was beneficial for the promotion of low-temperature combustion and the reduction of soot generation. This research provides a detailed investigation on the spray and combustion process and it highlights the significant effect of spray/wall interaction on the subsequent combustion process.
Review of road surface photometry methods and devices – Proposal for new measurement geometries
Authors: Muzet V , Bernasconi J , Iacomussi P , Liandrat S , Greffier F , Blattner P , Reber J , Lindgren M
Published: October 2020

Specifications concerning road lighting and photometry of road surfaces were established more than 50 years ago. Road lighting design and road marking visibility were developed for vehicle driving. The observation distance defined by standards corresponds to interurban applications; however, within Europe these areas do not tend to be lit. The objective of the SURFACE project is to propose new geometries for the photometric characterisation of pavements, both adapted to different urban travel modes and new lighting technologies. This article reviews the available guidelines, standards, measuring devices and literature regarding geometries and road lighting applications, and presents the project SURFACE analysis and proposal. The SURFACE consortium recommends adding several new angles for different driving conditions and road users; 2.29° for urban environments and consistency with road marking standard, and 1° for extra-urban environment and consistency with previous geometries. A 5° angle, corresponding to 17-m viewing distance, could be an interesting compromise, suitable for urban driving at low speed, cycling and for scooters. The angles of 10° and 20° are under consideration for describing the boundary between diffuse and specular behaviour.
Stand-Alone Thoracoscopic Left Atrial Appendage Closure in Nonvalvular Atrial Fibrillation Patients at High Bleeding Risk
Authors: Franciulli Marco , De Martino Giuseppe , Librera Mariateresa , Desoky Ahmed , Mariniello Antonio , Iavazzo Annarita , Scigliano Fabio , Esposito Giampiero , Chiariello Luigi
Published: October 2020

Objective

In nonvalvular atrial fibrillation (AF) patients at high bleeding risk, oral anticoagulants (OAC) may be contraindicated, and percutaneous left atrial appendage (LAA) closure has been advocated. However, following percutaneous procedure, either OAC or dual antiplatelet treatment is required. In this study, we present our experience in treating nonvalvular AF patients at high bleeding risk with thoracoscopic LAA closure with no subsequent antithrombotic therapy.

Methods

From April 2019 to January 2020, 20 consecutive AF patients, mean age 75.1 years, 16 (80%) males, underwent thoracoscopic LAA closure as a stand-alone procedure, using an epicardial clip device. OAC and antiplatelet therapy were contraindicated. Mean CHA2DS2-VASc score was 3.61, and the mean HAS-BLED score was 4.42. Successful LAA closure was assessed by transesophageal echocardiography. Primary endpoints were complete LAA closure (no residual LAA flow), operative complications, and all-cause mortality; secondary endpoints were 30-day and 6-month complications (death, ischemic stroke, hemorrhagic stroke, transient ischemic attack, any bleeding). Mean follow-up was 6 ± 4 months.

Results

Complete LAA closure was achieved in all patients. No operative clip-related complications or deaths occurred. At follow-up, freedom from postoperative complications was 95% and from any cerebrovascular events was 100%. Overall survival rate was 100%.

Conclusions

In nonvalvular AF patients at high bleeding risk (HAS-BLED score >3), thoracoscopic LAA closure appears to be a valid alternative to percutaneous techniques not requiring dual antiplatelet or OAC treatment. Apparently, external LAA clipping minimizes the risk of thromboembolic events as compared with percutaneous procedures.
Aortic wall elasticity and left ventricular function in hypertensive patients with nonsignificant coronary artery disease
Authors: Nabati Maryam , Namazi Shojaoddin , Yazdani Jamshid
Published: October 2020

Purpose

Hypertension is an important cause of nonischemic heart failure. It is important to identify subclinical left ventricular dysfunction in patients with hypertension in an early stage to lower the risk of progression to more severe illness. The aim of our study was to assess the correlation between indices of left ventricular function and aortic stiffness in patients with hypertension.

Methods

Our study was a case control study of 42 hypertensive and 40 normotensive patients with nonsignificant coronary artery disease. All the patients underwent echocardiography and left ventricular ejection fraction, global longitudinal strain, post systolic index, pulsed Doppler early transmitral peak flow velocity, early diastolic mitral annular velocity (e′), and aortic elasticity measurements were calculated.

Results

The hypertensive patients were older (58.47 ± 9.57 vs. 52.94 ± 10.38 years, p = 0.018) and had a higher body mass index (30.09 ± 5.08 vs. 27.48 ± 4.17 kg/m2, p = 0.013) and E/e′ ratio (8.16 ± 1.81 vs. 6.56 ± 1.71, p < 0.001) and a lower e′ velocity (8.25 ± 2.28 vs. 9.52 ± 2.34 cm/s, p = 0.015) than normotensives. They also had a lower aortic distensibility ( p = 0.008) and a higher aortic stiffness index ( p = 0.039) compared with the normotensive group. The hypertensive patients did not show any association between aortic elasticity and stiffness with age or e′ velocity despite significant association in normotensives.

Conclusion

Hypertension is associated with a high prevalence of diastolic dysfunction, elevated left ventricular filling pressure, and increased arterial stiffness, all of which have significant association with adverse outcomes. The measurements found in the hypertensive patients compared with the normotensive group may be due to several age-independent mechanisms.
Spontaneous Ocular Scanning of Visual Symmetry Is Similar During Classification and Evaluation Tasks
Authors: Makin Alexis D. J. , Poliakoff Ellen , Rampone Giulia , Bertamini Marco
Published: October 2020

Visual symmetry perception and symmetry preference have been studied extensively. However, less is known about how people spontaneously scan symmetrical stimuli with their eyes. We thus examined spontaneous saccadic eye movements when participants ( N = 20) observed patterns with horizontal or vertical mirror reflection. We found that participants tend to make saccades along the axis of reflection and that this oculomotor behaviour was similar during objective classification and subjective evaluation tasks. The axis-scanning behaviour generates a dynamic sequence of novel symmetrical images from a single static stimulus. This could aid symmetry perception and evaluation by enhancing the neural response to symmetry.
The Use of Intranasal Midazolam in a Special Care Dentistry Department: Technique and Cases
Authors: Drysdale David
Published: October 2020

Intranasal (IN) administered midazolam has allowed patients who require conscious sedation but struggle to tolerate cannulation another option by which they can receive dental treatment. Studies have demonstrated that a mean bioavailability ( F) of more than 73% can be achieved with IN-administered midazolam. This is due to the high vascularity within the nose. These studies have also demonstrated that peak plasma concentrations can be reached within 10 minutes. This signifies a fast onset of action. The standard bolus dose of IN midazolam is 10mg; this bolus can be reduced or increased depending on the patient's age and susceptibility to benzodiazepines. The bolus can also be repeated if adequate sedation is not reached. A protocol for administering IN midazolam is outlined and two cases are discussed.
Giving a Voice to the Person in My Dental Chair: Communication with People with Learning Disabilities
Authors: Hollingsworth Lorna , Kalambouka Afroditi
Published: October 2020

This article aims to increase the dental teams’ awareness of communicating with people with learning disabilities who have additional communication impairments. The paper presents a brief account of the factors behind why some people with learning disabilities may find it difficult to verbally communicate, and highlights the importance of ensuring high levels of care for all patients. It provides an overview of the principles of communication development and some of the most commonly used augmentative and alternative communication approaches. The paper concludes with suggestions of simple communication techniques as well as practical ideas, which can be easily incorporated into daily general dental practice in order to increase opportunities for successful interactions and minimise communication breakdown. By becoming more aware of the range of communication methods used to support those who have learning disabilities, the dental team will be more able to provide a better experience to their patients and ensure that their needs are met.
Medical Emergencies: Risk Assessment and Management
Authors: Greenwood Mark , Greenwood Mark
Published: October 2020

Dental practitioners need to have knowledge of the risk assessment, diagnosis and management of medical emergencies. This paper deals with risk assessment and basic management principles, applicable to all emergencies. More specific aspects of medical emergency management are also discussed.
Perioperative Surgical Pain Management
Authors: Khawaja Nadine
Published: October 2020

Acute dental pain continues to be under-managed, despite availability of several effective over-the-counter analgesics. This article discusses the mechanisms underlying the pain experience, the impact of post-operative pain and how to overcome barriers to optimal pain management. Prescribing using principles of multi-modal analgesia will be covered as well as discussion of associated side effects.
Optimal Local Anaesthesia for Dentistry
Authors: Renton Tara
Published: October 2020

Dentistry is unique in that high-volume surgery is undertaken efficiently on conscious patients, an anathema to most other surgical specialties, who predominantly operate on unconscious patients. Local anaesthesia (LA) provides an efficient block to nociceptive pain (the first stage of the pain pathway) but only addresses one small part of the pain experience. Currently the inferior dental block is the “go to” standard for dental LA for mandibular dentistry, despite its significant short comings. Unfortunately, habit means that we continue to practise what is taught to us at dental school, thus, not developing safer modern LA practice.

The dental syringe and deep injections are also the main triggers for fear and anticipated pain by patients expecting their dental appointment. The uptake of infiltration dentistry has been swift in implant dentistry, despite lack of an evidence base, and now other branches of specialty dentistry, general practice is awakening to the advantages of infiltration or “smart” local anaesthetic practices.

Inferior dental blocks are inefficient in providing swift pulpal anaesthesia. Stanley Malamed stated: “The rate of inadequate anaesthesia ranged from 31% to 81%, which when expressed as success rates, indicates a range of 19% to 69%. These numbers are so wide ranging as to make selection of a standard for rate of success for inferior alveolar nerve block (IANB) seemingly impossible”.

Any block injection is also associated with an increase in the risk of systemic and local complications (including nerve injury), possible heightened medical complications and patient discomfort and fear. Fear of deep dental injections is a key factor in dental anxiety and phobia.
A direct comparison of women’s perceptions and acceptability of micronised progesterone and medroxyprogesterone acetate in combination with transdermal oestradiol in the management of young postmenopausal women, under 45 years of age
Authors: Mittal M , Panay N , Supramaniam PR , Savvas M , Cardozo L , Hamoda H
Published: October 2020

Objective

To assess the acceptability and perception of postmenopausal women, to two different hormone replacement therapy regimens, in relation to the control of their symptoms and development of adverse effects.

Study design

Prospectively recruited postmenopausal women, <45 years, were randomised to one of two treatment arms for 12-months: cyclical micronised progesterone or medroxyprogesterone acetate in combination with transdermal oestradiol. A self-reported questionnaire with matrix rating scales was completed and repeated after 3, 6 and 12-months.

Main outcome measures

Symptom control and development of adverse effects.

Results

Seventy-one individuals were screened, with baseline data available for 67 subjects. A total of 190 questionnaires were returned. The most commonly reported symptoms were low energy levels, vasomotor symptoms and sexual dysfunction. The prevalence of adverse effects ranged between 57.89 and 87.50%, with a reduction seen in the transdermal oestradiol + micronised progesterone arm (73.91% at 3-months, decreasing to 57.89% at 12-months; p = 0.33), compared to the transdermal oestradiol + medroxyprogesterone acetate arm (76.92% at 3-months, increasing to 87.50% at 12-months; p = 0.69). The main reported adverse effects were bloating, weight change and psychological symptoms. A significant difference was documented between the groups after set intervals, with a greater proportion reporting breast tenderness after 3-months (p = 0.01), lower numbers reporting mood swings at 6-months (p = 0.01) and irritability at 12-months (p = 0.03) in the transdermal oestradiol + micronised progesterone arm compared to the transdermal oestradiol + medroxyprogesterone acetate arm.

Conclusions

The acceptability of both regimens was high despite adverse effects, but tolerability of transdermal oestradiol combined with micronised progesterone appeared to be better with fewer women reporting psychological concerns.
Text message reminders as an adjunct to a substance use intervention for adolescents and young adults: Pilot feasibility and acceptability findings
Authors: Schwebel Frank J , Larimer Mary E
Published: October 2020

Objective

Text messaging has been proposed as a method for increasing the reach of interventions for harmful alcohol and other drug use. This paper describes the design of an automated text messaging adjunct to a substance use intervention intended to support adolescents and young adults attempting to change their alcohol and other drug use behavior. Feasibility and acceptability testing was conducted as part of this pilot study.

Method

Five focus groups were conducted to refine text message content and finalize pilot intervention design. Automated, daily, substance use-related reminder text messages were sent to pilot intervention participants ( n = 39), who were recruited from outpatient treatment.

Results

Of those who were invited, 63% enrolled in the study and 89.7% remained enrolled in the study as measured by completing at least one assessment after baseline. Participants reported a positive experience with the messages, particularly supportive/empowering messages and commitment reminder messages.

Conclusions

These findings suggest that text messaging is a feasible and acceptable method for delivery of substance use-related reminder content as an adjunct to substance use intervention.
Long-term worsening of different body functions in persons with progressive multiple sclerosis
Authors: Kaufmann Marco , Vaney Claude , Barin Laura , Liu Xinglu , von Wyl Viktor
Published: October 2020

Background

It is unclear whether EDSS is responsive to disability worsening in advanced MS.

Objective

To explore the dynamics of disability worsening in persons with advanced-stage MS (EDSS ≥5.5) using three disability worsening definitions (EDSS, Rivermead Mobility Index (RMI), 9-Hole Peg Test (9-HPT)).

Methods

EDSS-, RMI- and 9-HPT-based disability worsening were assessed over a minimum of two years in a cohort of 286 persons with advanced MS attending inpatient rehabilitation using Kaplan-Meier Curves and multivariable Cox regression. Furthermore, the correspondence between EDSS-, RMI- and 9-HPT-based disability worsening was analyzed.

Results

Disability progression was observed in 49% (9-HPT), 52% (EDSS) and 53% (RMI), with 9-HPT-based worsening slightly lagging behind. The Multiple Sclerosis Severity Score (MSSS) was the only consistent factor predicting disability worsening based on all three definitions (EDSS: hazard ratio 1.48 [1.30;1.68]; RMI: 1.12 [0.99;1.27]; 9-HPT: 1.36 [1.18;1.57]). Correspondence between EDSS and the other definitions (9-HPT and RMI) was 44.3% and 55.7% at time of EDSS progression and 65.1% and 72.5% overall, respectively.

Conclusion

In persons with advanced-stage MS, half still developed disability worsening in different functional systems over a median of 6 years. MSSS seems a valid predictor for disability worsening in all three outcome measures in advanced MS.
Is There Clinical Improvement Associated With Intradiscal Therapies? A Comparison Across Randomized Controlled Studies
Authors: Ju Derek G. , Kanim Linda E. , Bae Hyun W.
Published: October 2020

Study Design:

Post hoc comparison using single-site data from 4 multicenter randomized controlled trials.

Objectives:

Discogenic back pain is associated with significant morbidity and medical cost. Several terminated, unreported randomized controlled trials have studied the effect of intradiscal biologic injections. Here we report single-center outcomes from these trials to determine if there is clinical improvement associated with these intradiscal injections.

Methods:

Post hoc comparison was performed using single-site data from 4 similar multi-center randomized controlled trials. All trials evaluated an injectable therapy (growth factor, fibrin sealant, or stem cells) for symptomatic lumbar disc disease with near-identical inclusion and exclusion criteria. Demographics and patient reported outcomes were analyzed across treatment arms postinjection.

Results:

A total of 38 patients were treated with biologic agents and 12 were treated with control saline injections. There was a significant decrease in visual analogue score (VAS) pain for both the investigational and saline groups up to 12 months postinjection ( P < .01). There was no significant difference in VAS scores between the saline and investigational groups at 12 months. Similarly, there was significant improvement in patient-reported disability scores in both the investigational and saline groups at all time points. There were no significant differences in disability score improvement between the saline and investigational treatment groups at 12 months postinjection.

Conclusions:

A single-center analysis of 4 randomized controlled studies demonstrated no difference in outcomes between therapeutic intradiscal agents (growth factor, fibrin sealant, or stem cells) and control saline groups. In all groups, patient reported pain and disability scores decreased significantly. Future studies are needed to evaluate the therapeutic benefit of any intradiscal injections.
Strategic Decisions Related to Circular Business Model in a Forerunner Company: Challenges Due to Path Dependency and Lock-In
Authors: Lehtimäki Hanna , Piispanen Ville-Veikko , Henttonen Kaisa
Published: October 2020

Circular economy (CE) entails a radical change in companies because new ways of thinking and doing business are required for value-creation opportunities. There is a lack of empirical studies on how companies themselves see and develop the CE business. Furthermore, the dynamics between the changes required when pursuing a circular business model (CBM) have not been sufficiently studied. This intensive case study examines the strategic business decisions of a forerunner company in CE over 20 years.

Questions: What were the strategic decisions related to CE business model in the case company over 20 years? What internal and external factors impacted the strategic decisions and how?

Theory: The theoretical framework of this study is built based on CBM strategies and capabilities in the CE business.

Basis of the Case: Phenomenon.

Type of the Case: An intensive case study of a forerunner company in CE.

Protagonist: Not needed.

Findings: First, the results of the analysis show that the company engaged in both slowing and closing resource loop business model strategies in the CE market. Second, the results of the analysis imply that the path dependency in the market was too strong, and the company was not able to break the path dependency of the closing loop strategy. Third, the results show that the case company was, however, able to challenge the path dependency and lock-in in the closing resource loop strategy with internal factors that included strategic management capabilities, such as making decisions within the current market conditions, organizational capabilities, such as developing new positions and knowledge, technological capabilities, such as investments on improving and upgrading recycling and waste management, and business model innovation capabilities.

Discussions: This study contributes to a call for further research on how companies themselves see and develop CE business. This study sheds light on the ways by which path dependency and lock-in contribute to CBM innovation and can explain a CE strategy failure. Furthermore, this study provides evidence that by drawing on company-internal and company-external factors, a company can challenge path dependency and lock-in and go forward in developing the CE business despite difficulties. For the case company, it was easier to maintain the closing resource loop strategy and stay with the original core business idea of providing recycling and waste management services to construction businesses and selling waste material for energy and heat production than engaging in slowing resource loop strategy. Finally, the results of this study suggest that path dependency theory is useful in projecting future risks in CBM innovation.
The Operation Rainbow Canada Technique for Unilateral Cleft Lip Revision
Authors: White Colin , Ukani Hanif , Rai Kimit
Published: October 2020

Background:

Purpose of this article is to demonstrate the “Operation Rainbow Canada” cleft lip revision technique. This is a surgical technique used by Operation Rainbow Canada on volunteer surgical missions in developing nations. We show how to convert previous Millard or straight line cleft lip repairs to a Fisher anatomic subunit repair, placing a favourable scar along the philtrum. We show a case series of results and explain how this technique gives satisfying aesthetic results for patients seeking unilateral cleft lip revision.

Methods:

This technique combines the principles of the anatomic subunit repair for primary cleft lip repair as described by Fisher and the correction of the cleft nose deformity as described by McComb. We apply these 2 techniques to unilateral cleft lip revision at the same operation.

Results:

Patients for revision unilateral lip and nose deformities were treated with this technique over the course of several international surgical missions. There were over 90 cases of revisions performed by our group on previous repaired cleft lips. These procedures were done in India, China, and Cambodia.

Conclusion:

Previously repaired cleft lips can be improved by our revision procedure. We show how incorporating 2 triangular flaps to lengthen the cleft side of the repaired lip can be done in a revision setting. During lip revision, McCombs sutures can be placed to improve the aesthetic of the nose and correct the nasal alar dome.
An Aggressive Presentation of Merkel Cell Carcinoma: A Case Report
Authors: Ines Zemni , Sabrine Haddad , Saadallah Fatma , Mohamed Ali Ayadi , Lamia Charfi , Riadh Chargui , Khaled Rahal
Published: October 2020

Merkel cell carcinoma (MCC) is a rare malignant neuroendocrine tumor more common in immunosuppressed old patients. It is characterized by a high frequency of local recurrence, regional nodal metastasis, distant metastasis, and low survival rate. The diagnosis of MCC is challenging due to its rarity and can be clinically mistaken for other skin cancer. We report a case of locally advanced MCC of the left groin with aggressive behavior that was finally controlled with a combined treatment and we collected data from the literature to discuss the appropriate therapeutic algorithm for the management of this uncommon skin tumor.
Envelope use and reporting in randomised controlled trials: A guide for researchers
Authors: Clark Laura , Dean Alexandra , Mitchell Alex , Torgerson David J
Published: October 2020

Introduction

To produce robust evidence RCTs need to be rigorously conducted as poorly performed studies introduce bias and can mislead clinicians and policy makers. Poor allocation concealment has the largest single impact on bias in RCTs than other methodological aspects. Envelopes are frequently used as a method of allocation concealment and can be associated with increased risk of bias. This paper aims to review envelope use in RCTs published in 2017–2018 and create a guide as a reference for researchers when planning and publishing RCTs when using envelopes as an allocation concealment method.

Methods

RCTs that used envelopes as a form of allocation concealment that were published in BMJ, JAMA, NEJM and The Lancet in 2017 and 2018 were identified and methodological data on their envelope use extracted and authors were contacted to ascertain reasons for using envelopes in their research.

Results

338 RCTs were identified that were published in 2017 and 2018. 8% (n = 29) of the RCTs published used envelopes as an allocation concealment method. 24.1% (n = 7) of studies reported envelope studies robustly with all required methodological information stated to enable an assessment of quality. Budget was the most frequent reason given for envelope use (41.7%).

Discussion

Only 24% of published RCTs, that used envelopes, contained robust methodological information to enable the reader to judge whether the randomisation and allocation concealment method was adequate.

Conclusion

RCTs are not reporting envelope use well. RCTs using envelopes should be designed and reported clearly ensuring all necessary methodological information is included.
Antiepileptic Drugs–Induced Enuresis in Children: An Overview
Authors: Sathyan Arya , Scaria Reshma , Arunachalam Pavithra , Ramasamy Mohanapriya , Thekkekkara Dithu , Sivadasan Shalini
Published: October 2020

Objective: To evaluate enuresis-induced antiepileptic drugs in children. Data Sources: A PubMed search (1917 to July 2020) was performed using the following keywords and associated medical subject headings: antiepileptic drugs, enuresis, pediatric population, drug-induced enuresis, and epilepsy. Study Selection and Data Extraction: The search was conducted to find the role of antiepileptic drugs–induced enuresis in children in studies published in English. Data Synthesis: Enuresis or bedwetting is an underreported adverse drug reaction of antiepileptic drugs. Owing to that fact, it is a condition that is outgrown with age and also could cause embarrassment. As antiepileptic drugs sometimes need to be taken for a long duration until epilepsy relapses, the occurrence of enuresis in this situation can be troublesome for both the child and the caretaker. Even though enuresis is proposed to have a significant effect on the child’s psychology, it is still considered to be a condition that is outgrown with age. This article includes a review of antiepileptic drugs reported to have caused enuresis in children. Conclusions: If a child develops enuresis as an adverse drug reaction, this adds further challenges to their life. A better understanding of this potential adverse effect may help prevent unwanted stress. Though the exact mechanisms are not known, the hypothesis generated is from the occurred cases, most of which relapsed when the drug was withdrawn. Considering the gravity of epilepsy in children, more detailed studies need to be conducted on this adverse effect to ensure a safe and effective treatment in children.
HLA-A alleles influencing NK cell function impact AML relapse following allogeneic hematopoietic cell transplantation
Authors: van der Ploeg Kattria , Le Luduec Jean-Benoît , Stevenson Philip A. , Park Soo , Gooley Ted A. , Petersdorf Effie W. , Shaffer Brian C. , Hsu Katharine C.
Published: October 2020

HLA-B allotypes exhibiting the Bw4 epitope trigger variable inhibitory signaling of KIR3DL1 receptor types, where strong inhibitory HLA-B and KIR3DL1 allele combinations are associated with increased risk for relapse of acute myelogenous leukemia (AML) following allogeneic hematopoietic cell transplantation (HCT). Several HLA-A allotypes also exhibit the Bw4 epitope. Studies with natural killer (NK) cell clones have demonstrated NK inhibition via KIR3DL1 by HLA-A Bw4+ allotypes, but did not delineate strengths of inhibition or hierarchies of NK education. Using primary NK cells from healthy donors, we demonstrate that HLA-A*23, HLA-A*24, and HLA-A*32 proteins are expressed at different densities and exhibit different capacities to educate and inhibit KIR3DL1-expressing NK cells in vitro. Among the HLA-A Bw4+ allotypes, HLA-A*24 and HLA-A*32 demonstrate the strongest inhibitory capacity. To determine if HLA-A allotypes with strong inhibitory capacity have similar negative impact in allogeneic HCT as HLA-B Bw4+ allotypes, we performed a retrospective analysis of 1729 patients with AML who received an allogeneic HCT from a 9/10 or 10/10 HLA allele-matched unrelated donor. Examination of the donor-recipient pairs whose Bw4 epitope was exclusively contributed from HLA-A*24 and A*32 allotypes revealed that patients with HLA-A*24 who received an allograft from a KIR3DL1+ donor experienced a higher risk of disease relapse (hazard ratio, 1.65; 95% confidence interval, 1.17-2.32; P = .004) when compared with patients without a Bw4 epitope. These findings indicate that despite weak affinity interactions with KIR3DL1, common HLA-A allotypes with the Bw4 epitope can interact with KIR3DL1+ donor NK cells with clinically meaningful impact and provide additional insight to donor NK alloreactivity in HLA-matched HCT.
Observational studies assessing the pharmacological treatment of obstructive lung disease: strengths, challenges and considerations for study design
Authors: Vestbo Jørgen , Janson Christer , Nuevo Javier , Price David
Published: October 2020

Randomised controlled trials (RCTs) are the gold standard for evaluating treatment efficacy in patients with obstructive lung disease. However, due to strict inclusion criteria and the conditions required for ascertaining statistical significance, the patients included typically represent as little as 5% of the general obstructive lung disease population. Thus, studies in broader patient populations are becoming increasingly important. These can be randomised effectiveness trials or observational studies providing data on real-world treatment effectiveness and safety data that complement efficacy RCTs.

In this review we describe the features associated with the diagnosis of asthma and chronic obstructive pulmonary disease (COPD) in the real-world clinical practice setting. We also discuss how RCTs and observational studies have reported opposing outcomes with several treatments and inhaler devices due to differences in study design and the variations in patients recruited by different study types. Whilst observational studies are not without weaknesses, we outline recently developed tools for defining markers of quality of observational studies. We also examine how observational studies are capable of providing valuable insights into disease mechanisms and management and how they are a vital component of research into obstructive lung disease.

As we move into an era of personalised medicine, recent observational studies, such as the NOVEL observational longiTudinal studY (NOVELTY), have the capacity to provide a greater understanding of the value of a personalised healthcare approach in patients in clinical practice by focussing on standardised outcome measures of patient-reported outcomes, physician assessments, airway physiology, and blood and airway biomarkers across both primary and specialist care.
Isolated night cough in children: how does it differ from wheeze?
Authors: Jurca Maja , Goutaki Myrofora , Latzin Philipp , Gaillard Erol A. , Spycher Ben D. , Kuehni Claudia E.
Published: October 2020

It has been postulated that some children with recurrent cough but no wheeze have a mild form of asthma (cough variant asthma), with similar risk factors and an increased risk of future wheeze.

This longitudinal study compared risk factors for isolated night cough and for wheeze in the Leicester Respiratory Cohort in children aged 1, 4, 6 and 9 years and compared prognosis of children with isolated night cough, children with wheeze and asymptomatic children.

We included 4101 children aged 1 year, 2854 aged 4 years, 2369 aged 6 years and 1688 aged 9 years. The prevalence of isolated night cough was 10% at age 1 year and 18% in older children. Prevalence of wheeze decreased from 35% at 1 year to 13% at 9 years. Although several risk factors were similar for cough and wheeze, day care, reflux and family history of bronchitis were more strongly associated with cough, and male sex and family history of asthma with wheeze. Over one-third of preschool children with cough continued to cough at school age, but their risk of developing wheeze was similar to that of children who were asymptomatic at earlier surveys. Wheeze tracked more strongly throughout childhood than cough.

In conclusion, our study showed that only some risk factors for cough and wheeze were shared but many were not, and there was little evidence for an increased risk of future wheeze in children with isolated night cough. This provides little support for the hypothesis that recurrent cough without wheeze may indicate a variant form of asthma.
Multiple breath washout in bronchiectasis clinical trials: is it feasible?
Authors: O'Neill Katherine , Ferguson Kathryn , Cosgrove Denis , Tunney Michael M. , De Soyza Anthony , Carroll Mary , Chalmers James D. , Gatheral Timothy , Hill Adam T. , Hurst John R. , Johnson Christopher , Loebinger Michael R. , Angyalosi Gerhild , Haworth Charles S. , Jensen Renee , Ratjen Felix , Saunders Clare , Short Christopher , Davies Jane C. , Elborn J. Stuart , Bradley Judy M.
Published: October 2020

Background

Evaluation of multiple breath washout (MBW) set-up including staff training, certification and central “over-reading” for data quality control is essential to determine the feasibility of MBW in future bronchiectasis studies.

Aims

To assess the outcomes of a MBW training, certification and central over-reading programme.

Methods

MBW training and certification was conducted in European sites collecting lung clearance index (LCI) data in the BronchUK Clinimetrics and/or i-BEST-1 studies. The blended training programme included the use of an eLearning tool and a 1-day face-to-face session. Sites submitted MBW data to trained central over-readers who determined validity and quality.

Results

Thirteen training days were delivered to 56 participants from 22 sites. Of 22 sites, 18 (82%) were MBW naïve. Participant knowledge and confidence increased significantly (p<0.001). By the end of the study recruitment, 15 of 22 sites (68%) had completed certification with a mean (range) time since training of 6.2 (3–14) months. In the BronchUK Clinimetrics study, 468 of 589 (79%) tests met the quality criteria following central over-reading, compared with 137 of 236 (58%) tests in the i-BEST-1 study.

Conclusions

LCI is feasible in a bronchiectasis multicentre clinical trial setting; however, consideration of site experience in terms of training as well as assessment of skill drift and the need for re-training may be important to reduce time to certification and optimise data quality. Longer times to certification, a higher percentage of naïve sites and patients with worse lung function may have contributed to the lower success rate in the i-BEST-1 study.
Validation of the Moroccan arabic version of the low anterior resection syndrome score
Authors: Essangri Hajar , Majbar Mohammed Anass , Benkabbou Amine , Amrani Laila , Mohsine Raouf , Souadka Amine
Published: October 2020

Background

Sphincter sparing surgery is oftentimes associated with bowel dysfunction complaints, namely the low anterior resection syndrome (LARS). The LARS questionnaire is widely used to assess this syndrome. The aim of this observational study is to translate this tool into arabic and test its psychometric properties in rectal cancer patients, in order to ease its use in clinical practice and future research.

Methods

The LARS questionnaire was translated to arabic and administered to a total of 143 patients. A subgroup of 42 patients took the test twice for test-retest reliability. Internal consistency was examined through cronbach’s alpha. The score results were correlated to the EORTC QLQ-C30 questionnaire for convergent validity assessment, while discriminant validity was established through the ability of the LARS score to differentiate patients with different clinical and pathological criteria.

Results

The Moroccan Arabic version of the LARS score was completed by 143 patients. The internal consistency was demonstrated through a cronbach alpha score of 0.66. The agreement between the test and retest was established by a Bland Altman plot with 95% limits of agreement. 85.6% of patients remained in the same LARS category. The LARS score showed negative correlation with all five of the QLQ-C30 functional scales as well as positive correlation to the diarrhea symptom scale. The questionnaire score differed between patients according to their tumor location, chemoradiotherapy, type of mesorectal excision and anastomosis.

Conclusion

The Moroccan Arabic version of the LARS score shows good psychometric properties and can be used for bowel dysfunction assessment in clinical and research settings.
Impact of concomitant systemic treatments on toxicity and intracerebral response after stereotactic radiotherapy for brain metastases
Authors: Guénolé Morgan , Lucia François , Bourbonne Vincent , Dissaux Gurvan , Reygagne Emmanuelle , Goasduff Gaëlle , Pradier Olivier , Schick Ulrike
Published: October 2020

Background

The aim of this study was to determine the safety and efficacy of fractionated stereotactic radiotherapy (SRT) in combination with systemic therapies (ST) for brain metastases (BM).

Methods

Ninety-nine patients (171 BM) received SRT and concurrent ST (group 1) and 95 patients (131 BM) received SRT alone without concurrent ST (group 2). SRT was planned on a linear accelerator, using volumetric modulated arc therapy. All ST were allowed including chemotherapy (CT), immunotherapy (IT), targeted therapy (TT) and hormonotherapy (HT). Treatment was considered to be concurrent if the timing between the drug administration and SRT did not exceed 1 month. Local control (LC), freedom for distant brain metastases (FFDBM), overall survival (OS) and radionecrosis (RN) were evaluated.

Results

After a median follow-up of 11.9 months (range 0.7–29.7), there was no significant difference between the two groups. However, patients who received concurrent IT (n = 30) had better 1-year LC, OS, FFDBM but a higher RN rate compared to patients who did not: 96% versus 78% (p = 0.02), 89% versus 77% (p = 0.02), 76% versus 53%(p = 0.004) and 80% versus 90% (p = 0.03), respectively. In multivariate analysis, concurrent IT (p = 0.022) and tumor volume < 2.07 cc (p = 0.039) were significantly correlated with improvement of LC. The addition of IT to SRT compared to SRT alone was associated with an increased risk of RN (p = 0.03).

Conclusion

SRT delivered concurrently with IT seems to be associated with improved LC, FFDBM and OS as well as with a higher rate of RN.