bluuebunny/crossref_metadata_2025 huggingface dataset:
The Audit Reform and Non-Audit Services in the Light of the Big-4 Transparency Reports – the EU Perspective
Authors: Indyk Magdalena
Published: November 2020

The aim of this article is to compare and contrast three different approaches towards non-audit services (henceforth “NAS”) based on: 1) researchers’ views, 2) the EU regulation, and 3) the provision of NAS by the Big-4 firms operating in twenty-seven EU member states. Therefore, the article includes: (i) a literature review of various NAS aspects, (ii) an analysis of the EU reform in terms of NAS, and (iii) an empirical analysis of NAS fees which have been disclosed in the Big-4 transparency reports for the period 2017-2019.The literature review shows: a) lack of consensus between researchers about the potential consequences of the NAS provision in general, b) quite limited or little evidence of the consequences of the NAS restrictions as part of the EU audit reform, c) ambiguity in terms of the NAS definition itself which results mainly from insufficient NAS disclosures and lack of a detailed NAS split.The EU regulators addressed these concerns only in very narrow aspects, i.e., through: (1) the NAS black list, (2) the NAS cap, and (3) the strong emphasis on public-interest entities (henceforth “PIEs”). What is more, NAS disclosure requirements in the transparency reports are limited only to two categories.Finally, the results of the empirical study indicate the significant differences at the NAS fee level among the EU member states. The analysis shows a particular importance of NAS fees from other clients as a substantial revenue stream for the Big-4 firms. The results suggest also a significant increase in this category in 2018 when NAS fees from other clients increased by net EUR809 million (13%). However, this strong trend was not confirmed in the following year.All in all, the study underlines deficiency in proper NAS disclosure and reporting which might be observed also in the case of transparency reports. All findings of this study may be another argument for regulators to address the problem of NAS in more detail starting from their advice on a NAS taxonomy which might be used then as a point of reference. It would be also beneficial for researchers exploring the NAS aspect and, thus, may enhance data and results comparability between studies. Additional disclosure requirements like NAS provided to PIEs or a recurring or non-recurring character of NAS would also support the better understanding and evaluation of the consequences of the EU audit reform.
Comprensión individual y diádica de tablas de frecuencias en alumnos de escolaridad primaria
Authors: Castellaro Mariano , Roselli Néstor
Published: November 2020

Objetivo. Analizar la integración entre comprensión individual y diádica de una tabla de frecuencias enestudiantes de primaria, cuyo foco estuvo en la calidad y cualidad del producto cognitivo. Método. Participaron 90 estudiantes de 6º y 7º grado (edad: M = 12.3; DE = 0.5), seleccionados no probabilísticamente. Primero, los sujetos resolvieron de forma individual la tarea de comprensión de una tabla de doble entrada. Luego fueron agrupados en díadas que resolvieron la tarea colaborativamente. Se utilizó un cuestionario para evaluar niveles de complejidad de dicha comprensión y centrar el análisis en: (a) la comparación de desempeños individual y diádico generales, (b) las modalidades de integración entre producción individual y diádica, y (c) las modalidades según complejidad del ítem y composición sociocognitiva diádica. Resultados. Se encontró: (a) superioridad del desempeño diádico sobre el individual, (b) se identificaron diferentes modalidades de integración entre comprensión individual y diádica, y (c) la influencia del nivel de complejidad del ítem y la composición sociocognitiva sobre modalidades específicas de respuesta construidas por la díada. Conclusión. Se corrobora la hipótesis de la superioridad de las actuaciones interindividuales sobre las intraindividuales, aunque con variaciones generadas por las variables mediadoras. Los hallazgos se discutieron según la diferenciación conceptual entre producto y proceso.
Estilos de comunicación como predictores del estrés y el afrontamiento diádico en matrimonios puertorriqueños
Authors: Nina-Estrella Ruth , Marrero-Centeno Jesús J.
Published: November 2020

Objetivo. Evaluar la posible relación de los estilos de comunicación (positivo, negativo y reservado) con elestrés y el afrontamiento diádico en las relaciones de pareja. Método. Se empleó un estudio cuantitativono experimental en el que participaron 121 personas casadas, seleccionadas por disponibilidad. La mayoríade los participantes estaban en su primer matrimonio, y tenían una edad promedio de 42 años. Aceptaroncontestar los siguientes instrumentos: (a) inventario de estilo de comunicación marital (ECOM) y (b) escala de estrés en la relación marital. Resultados. El análisis mediante regresión múltiple evidenció que los estilos de comunicación positivo y reservado son predictores del afrontamiento diádico. Se observó también que el estilo de comunicación negativo es un predictor significativo del estrés en las relaciones de pareja. Conclusión. Se sustenta la importancia de la comunicación en las relaciones de pareja y de desarrollar estilos de comunicación positivos para afrontar las situaciones estresantes.
Rate of Force Development, Muscle Architecture, and Performance in Elite Weightlifters
Authors: Zaras Nikolaos , Stasinaki Angeliki-Nikoletta , Spiliopoulou Polyxeni , Arnaoutis Giannis , Hadjicharalambous Marios , Terzis Gerasimos
Published: November 2020

Purpose: The purpose of the present study was to investigate the relationship between weightlifting performance and the rate of force development (RFD), muscle architecture, and body composition in elite Olympic weightlifters. Methods: Six male Olympic weightlifters (age 23.3 [3.4] y, body mass 88.7 [10.2] kg, body height 1.76 [0.07] m, snatch 146.7 [15.4] kg, clean and jerk 179.4 [22.1] kg), all members of the national team, participated in the study. Athletes completed a 16-week periodized training program aiming to maximize their performance at the national competition event. Measurements, including maximal strength (1-repetition maximum) in snatch, clean and jerk, back and front squat, isometric leg press RFD and peak force, countermovement jump, vastus lateralis muscle architecture, and body composition, were performed before and after the training period. Results: Weightlifting performance increased significantly after training (P < .05). Leg press RFD increased only in time windows of 0 to 200 and 0 to 250 milliseconds after training (8.9% [8.5%] and 9.4% [7.7%], respectively, P < .05) while peak force remained unaltered (P < .05). Front squat strength increased significantly (P < .05), while countermovement jump power increased 2.3% (2.1%) (P < .05). No changes were observed for muscle architecture and lean body mass (P > .05). Significant correlations were observed between performance in snatch and clean and jerk with isometric leg press RFD, at all time windows, as well as with lean body mass and squat 1-repetition maximum. Conclusions: These results suggest that regular examination of RFD, lean body mass, and lower extremities’ 1-repetition maximum may be useful performance predictors in elite Olympic weightlifters.
Divergent impacts of warming weather on wildlife disease risk across climates
Authors: Cohen Jeremy M. , Sauer Erin L. , Santiago Olivia , Spencer Samuel , Rohr Jason R.
Published: November 2020

Climate change alters disease risks

Climate change appears to be provoking changes in the patterns and intensity of infectious diseases. For example, when conditions are cool, amphibians from warm climates experience greater burdens of infection by chytrid fungus than hosts from cool regions. Cohen
et al.
undertook a global metanalysis of 383 studies to test whether this “thermal mismatch” hypothesis holds true over the gamut of host-pathogen relationships. The authors combined date and location data with a selection of host and parasite traits and weather data. In the resulting model, fungal disease risk increased sharply under cold abnormalities in warm climates, whereas bacterial disease prevalence increased sharply under warm abnormalities in cool climates. Warming is projected to benefit helminths more than other parasites, and viral infections showed less obvious relationships with climate change.

Science
, this issue p.
eabb1702
Architecture of the photosynthetic complex from a green sulfur bacterium
Authors: Chen Jing-Hua , Wu Hangjun , Xu Caihuang , Liu Xiao-Chi , Huang Zihui , Chang Shenghai , Wang Wenda , Han Guangye , Kuang Tingyun , Shen Jian-Ren , Zhang Xing
Published: November 2020

Green to the core

Light from the Sun powers most life on today's Earth in some way. The core of the photosynthetic apparatus where charge separation occurs, the reaction center (RC), is thought to have originated a single time and diverged, yielding new kinds of complexes adapted to different tasks and environments. Chen
et al.
now present an important missing puzzle piece in our understanding of the evolution of RCs: a cryo–electron microscopy structure of the homodimeric type I RC from a green sulfur bacterium bound to a light-harvesting protein. The observed cofactor and pigment arrangement explain biochemical features of this RC and will aid in our understanding of how a single ancestral RC gave rise to the range of structures and functions seen in RCs today.

Science
, this issue p.
eabb6350
Nanomesh pressure sensor for monitoring finger manipulation without sensory interference
Authors: Lee Sunghoon , Franklin Sae , Hassani Faezeh Arab , Yokota Tomoyuki , Nayeem Md Osman Goni , Wang Yan , Leib Raz , Cheng Gordon , Franklin David W. , Someya Takao
Published: November 2020

A soft touch

Measuring the force it takes for a hand to grasp an object requires sensors to be placed on the fingertips, but these sensors will interfere with or affect how much force ends up being applied. Lee
et al.
developed a nanomesh sensor built from a series of electrospun materials (see the Perspective by Liu). Using a robotic tester, they show that this device can repeatably detect the pressure involved in gripping an object. They also show that the sensors can be attached to human fingers and that this does not affect the force used to grasp an object.

Science
, this issue p.
966
; see also p.
910
Response to Comment on “Ancient origins of allosteric activation in a Ser-Thr kinase”
Authors: Wilson Christopher , Kern Dorothee
Published: November 2020

Park
et al
. question one out of seven findings from Hadzipasic
et al
.: whether TPX2 allosterically regulates the oldest Aurora. We had already addressed the two concerns raised—sparse sequence sampling and not forcing the gene to the species tree—before publication. Moreover, we believe their ancestral sequence reconstruction would be consistent with a nonallosteric common ancestor, and we show large sequence differences caused by species tree–enforced gene trees.
Enhanced Zika virus susceptibility of globally invasive
Aedes aegypti
populations
Authors: Aubry Fabien , Dabo Stéphanie , Manet Caroline , Filipović Igor , Rose Noah H. , Miot Elliott F. , Martynow Daria , Baidaliuk Artem , Merkling Sarah H. , Dickson Laura B. , Crist Anna B. , Anyango Victor O. , Romero-Vivas Claudia M. , Vega-Rúa Anubis , Dusfour Isabelle , Jiolle Davy , Paupy Christophe , Mayanja Martin N. , Lutwama Julius J. , Kohl Alain , Duong Veasna , Ponlawat Alongkot , Sylla Massamba , Akorli Jewelna , Otoo Sampson , Lutomiah Joel , Sang Rosemary , Mutebi John-Paul , Cao-Lormeau Van-Mai , Jarman Richard G. , Diagne Cheikh T. , Faye Oumar , Faye Ousmane , Sall Amadou A. , McBride Carolyn S. , Montagutelli Xavier , Rašić Gordana , Lambrechts Louis
Published: November 2020

Domesticating Zika virus

Why hasn't Zika virus (ZIKV) disease caused as much devastation in Africa, its continent of origin, as it has in the Americas? Outside of Africa, this flavivirus is transmitted by a ubiquitous mosquito subspecies,
Aedes aegypti aegypti
, which emerged from the African forerunner subspecies
A. aegypti formosus
and acquired a preference for human blood and a peridomestic lifestyle. Now, this subspecies colonizes many intertropical cities, aided by climate change and human trash. Aubry
et al.
tested 14 laboratory mosquito colonies for their relative susceptibility to ZIKV. Quantitative trait locus mapping showed differences on chromosome 2 between mosquitoes from Gabon and Guadeloupe. Mouse infection experiments revealed that African mosquitoes transmitted a smaller virus inoculum than the South American insects. Increased susceptibility coupled with the ability of
A. aegypti aegypti
to breed in any discarded object containing water has amplified the problematic nature of this virus as it has circumnavigated the world.

Science
, this issue p.
991
A marine microbiome antifungal targets urgent-threat drug-resistant fungi
Authors: Zhang Fan , Zhao Miao , Braun Doug R. , Ericksen Spencer S. , Piotrowski Jeff S. , Nelson Justin , Peng Jian , Ananiev Gene E. , Chanana Shaurya , Barns Kenneth , Fossen Jen , Sanchez Hiram , Chevrette Marc G. , Guzei Ilia A. , Zhao Changgui , Guo Le , Tang Weiping , Currie Cameron R. , Rajski Scott R. , Audhya Anjon , Andes David R. , Bugni Tim S.
Published: November 2020

Prospecting for antifungal molecules

Marine bacteria produce a plethora of natural products that often have unusual chemical structures and corresponding reactivity, which sometimes translate into a valuable biological function. Zhang
et al.
used a metabolomic screen to zero in on microbial strains from the microbiome of a sea squirt that produces a high diversity of chemical structures. They then screened these molecules for inhibition of fungi (see the Perspective by Cowen). A polycyclic molecule dubbed turbinmicin possessed potent antifungal activity against the multidrug-resistant fungal pathogens
Candida auris
and
Aspergillus fumigatus
. Preliminary mechanism-of-action and mouse toxicity studies suggest that this molecule works though a fungus-specific pathway and is well tolerated at therapeutic doses.

Science
, this issue p.
974
; see also p.
906
Scaffolding Activities Increase Performance and Lower Frustration with Genotype-to-Evolution Models in Molecular Genetics
Authors: Wilson Kristy
Published: November 2020

Conceptual modeling was introduced in molecular genetics so students could integrate topics and apply molecular reasoning and mechanisms to phenotype, inheritance, and population dynamics. Structure Mechanism Relationship Function (SMRF) models were introduced. SMRF models focus on the function of a specified system using structures/nouns in boxes and processes/relationships/verbs on arrows. This SMRF model formatting enables discussion, feedback, and assessment.  Scaffolding activities were introduced to provide students with support for modeling and were intended to decrease or prevent students’ frustration, intimidation, and discouragement during the learning process.  Comparing a semester without scaffolding activities to semesters with scaffolding results indicate the following benefits: 1) better performance on modeling on first exam, 2) less student resistance towards modeling, and 3) better use of class time.  This article has the training activity for SMRF modeling, scaffolding activities, a grading rubric, and selection of adaptable question prompts to make conceptual modeling more accessible to instructors.
Students Who Analyze Their Own Data in a Course-Based Undergraduate Research Experience (CURE) Show Gains in Scientific Identity and Emotional Ownership of Research
Authors: Cooper Katelyn M. , Knope Matthew L. , Munstermann Maya J. , Brownell Sara E.
Published: November 2020

While it has been established that course-based undergraduate research experiences (CUREs) lead to student benefits, it is less clear what aspects of CUREs lead to such gains. In this study, we aimed to understand the effect of students analyzing their own data, compared with students analyzing data that had been collected by professional scientists. We compared the experiences of students in a CURE investigating whether the extinction risk status of terrestrial mammals and birds is associated with their ecological traits. Students in the CURE were randomly assigned to analyze either data that they had collected or data previously collected by professional scientists. All other aspects of the student experience were designed to be identical. We found that students who analyzed their own data showed significantly greater gains in scientific identity and emotional ownership than students who analyzed data collected by professional scientists.
Immediate versus delayed sequential bilateral cataract surgery in children: a cost-effectiveness analysis
Authors: Cernat Alexandra , Jamieson Margaret , Kavelaars RuthAnne , Khalili Sina , Bhambhwani Vishaal , Mireskandari Kamiar , Moretti Myla E
Published: November 2020

Background/aims

Children with bilateral cataracts may undergo immediate sequential bilateral cataract surgery (ISBCS), which involves surgery on both eyes during the same general anaesthesia, or delayed sequential bilateral cataract surgery (DSBCS), which involves operating on each eye on separate days and requires a second anaesthesia. ISBCS is viewed with caution because of the risk of bilateral endophthalmitis. Proponents of ISBCS emphasise that the incidence of serious complications is low and is outweighed by benefits such as avoidance of multiple anaesthesia, faster visual rehabilitation and potential for decreased costs. However, there is a paucity of literature regarding the cost-effectiveness of ISBCS in children. We conducted a cost-effectiveness analysis to determine whether ISBCS is more cost-effective than DSBCS from the societal and health system perspectives in Ontario, Canada, which has a universal, single-payer system.

Methods

A retrospective analysis of children who underwent ISBCS or DSBCS at a tertiary referral paediatric hospital was conducted. A decision tree was constructed using TreeAge Pro 2018 software. Clear visual axis was the measure of effectiveness. A time horizon of 8 weeks postoperatively was adopted. Both direct and indirect costs were included.

Results

Fifty-three children were included, 37 in the ISBCS group and 16 in the DSBCS group. ISBCS and DSBCS were equally effective. ISBCS resulted in cost-savings of $3,776 (95% CI:−$4,641 to $12,578) CAD, per patient, from the societal perspective and $2,200 (95% CI:−$5,615 to $10,373) CAD per patient from the health system perspective.

Conclusion

ISBCS was less costly than DSBCS from both societal and health system perspectives while being equally effective.
Efficacy, safety and cost-effectiveness comparison between U-100 human regular insulin and rapid acting insulin when delivered by V-Go wearable insulin delivery device in type 2 diabetes
Authors: Mora Pablo F , Sutton David R , Gore Ashwini , Baliga Bantwal , Goldfaden Rebecca F , Nikkel Carla , Sink II John , Adams-Huet Beverley
Published: November 2020

Introduction

We compared the efficacy and safety of human regular insulin (HRI) versus rapid-acting insulin (RAI) in a type 2 diabetes population already using the V-Go insulin delivery device.

Research design and methods

This was a 14-week, multicenter, randomized, open-label, parallel-group, phase IV, non-inferiority study. Patients ≥21years of age, with inadequately controlled type 2 diabetes who were currently using the V-Go insulin delivery system with RAI, with glycated hemoglobin (HbA1c) ≥6.5% (≥48 mmol/L) to ≤12.5% (≤108 mmol/L) were randomized 1:1 to RAI continuation or switch to HRI. The primary outcome was estimated treatment difference (ETD) in HbA1c least-squares mean change from baseline at 14 weeks (prespecified non-inferiority hypothesis with 95% CI upper limit <0.4%). Primary analysis was by per protocol (PP); safety analysis was by intention to treat.

Results

We randomized 136 patients to continued RAI treatment (n=67) or HRI (n=69); 113 patients were included in the PP analysis (RAI, n=54; HRI, n=59). Mean change in HbA1c from baseline to study end was −0.60±1.1% (95% CI −0.90 to –0.29); −6.6±12.0 mmol/mol (95% CI −9.8 to −3.2) with HRI treatment and −0.38±1.3% (95% CI −0.70 to –0.05); −4.2±14.2 mmol/mol (95% CI −7.7 to −0.5) with RAI treatment, with ETD of −0.22% (95% CI −0.67 to 0.22); −2.4 mmol/mol (95% CI −7.3 to 2.4), p=0.007, confirming non-inferiority of HRI to RAI. No between-group differences in changes in total daily insulin doses, number of hypoglycemic values (≤70 mg/dL (≤39 mmol/L) or body weight were observed. No severe hypoglycemic events were reported. Direct pharmacy cost savings (−US$265.85; 95% CI −US$288.60 to −US$243.11; p<0.0001) were observed with HRI treatment.

Conclusions

Individuals with type 2 diabetes requiring insulin can be treated with V-Go wearable insulin delivery device using HRI, safely and effectively, and potentially at a much lower cost compared with RAI, which can lead to improved access to insulin therapy for these individuals.

Trial registration number

NCT03495908.
Establishment of a high-dependency unit in Malawi
Authors: Morton Ben , Banda Ndaziona Peter , Nsomba Edna , Ngoliwa Clara , Antoine Sandra , Gondwe Joel , Limbani Felix , Henrion Marc Yves Romain , Chirombo James , Baker Tim , Kamalo Patrick , Phiri Chimota , Masamba Leo , Phiri Tamara , Mallewa Jane , Mwandumba Henry Charles , Mndolo Kwazizira Samson , Gordon Stephen , Rylance Jamie
Published: November 2020

Adults admitted to hospital with critical illness are vulnerable and at high risk of morbidity and mortality, especially in sub-Saharan African settings where resources are severely limited. As life expectancy increases, patient demographics and healthcare needs are increasingly complex and require integrated approaches. Patient outcomes could be improved by increased critical care provision that standardises healthcare delivery, provides specialist staff and enhanced patient monitoring and facilitates some treatment modalities for organ support. In Malawi, we established a new high-dependency unit within Queen Elizabeth Central Hospital, a tertiary referral centre serving the country’s Southern region. This unit was designed in partnership with managers, clinicians, nurses and patients to address their needs. In this practice piece, we describe a participatory approach to design and implement a sustainable high-dependency unit for a low-income sub-Saharan African setting. This included: prospective agreement on remit, alignment with existing services, refurbishment of a dedicated physical space, recruitment and training of specialist nurses, development of context-sensitive clinical standard operating procedures, purchase of appropriate and durable equipment and creation of digital clinical information systems. As the global COVID-19 pandemic unfolded, we accelerated unit opening in anticipation of increased clinical requirement and describe how the high-dependency unit responded to this demand.
Indirect comparison between immunotherapy alone and immunotherapy plus chemotherapy as first-line treatment for advanced non-small cell lung cancer: a systematic review
Authors: Li Lingling , Xu Fei , Chen Yu , Ren Xiaoli , Liu Yu , Chen Yuan , Xia Shu
Published: November 2020

Objectives

Use of immune checkpoint inhibitors as first-line treatment for advanced (stage IIIB/IV) non-small cell lung cancer (NSCLC) remains controversial. Clinical trials comparing single-drug immunotherapy (IO) with immunotherapy plus chemotherapy (IC) are lacking. We aimed to compare the efficacy of IO alone with that of IC as first-line treatment for advanced NSCLC.

Design

Systematic review.

Data sources

PubMed, the Cochrane Library and Embase for related studies on NSCLC; ClinicalTrials.gov, American Society of Clinical Oncology Meeting Library and World Conference on Lung Cancer for relevant conference abstracts (to July 2019).

Eligibility criteria

Articles meeting the following criteria were selected: (1) randomised controlled trials on NSCLC treatment, (2) all individuals in the studies had not received treatment previously and (3) research on IO monotherapy using programmed death-1/programmed death ligand-1 (PD-L1) inhibitors or IC.

Data extraction and synthesis

After reading the original literature, two reviewers independently extracted the relevant information. The primary outcomes were progression-free survival (PFS), overall survival (OS) and objective response rate (ORR). We also extracted data on treatment-related adverse events and immune-related adverse events (irAEs).

Results

Overall, 10 randomised controlled clinical trials (n=5765) were included. As first-line treatment for advanced NSCLC, IC tended to yield better PFS, OS and ORR than did IO. Furthermore, IC yielded significantly better PFS than IO when tumour PD-L1 expression was at least 50% (HR: 1.81, 95% CI: 1.18 to 2.78) and yielded a better OS and PFS when tumour PD-L1 expression was at least 1%; IO resulted in fewer adverse events than did IC. However, the incidence of irAEs was higher for IO than for IC.

Conclusions

The findings of the indirect comparison indicate that IC as first-line treatment for advanced NSCLC is significantly more effective than IO in patients with PD-L1 expression in at least 50% of tumour cells.

Trial registration number

CRD 42018116589.
Optimum duration of adjuvant trastuzumab in treatment of human epidermal growth factor receptor-2 positive early breast cancer: protocol for a network meta-analysis of randomised controlled trials
Authors: Hu Qiancheng , Wang Xin , Chen Ye , Li Xiaofen , Luo Ting , Cao Dan
Published: November 2020

Introduction

Controversy regarding optimum duration of trastuzumab treatment remains in patients with human epidermal growth factor receptor-2 (HER2) positive early breast cancer. The objective of applying network meta-analysis (NMA) is to integrate existing evidence based on direct and indirect comparisons of efficacy and safety, and then to determine the duration of trastuzumab treatments with the greatest impact on therapeutic outcomes in HER2-positive early breast cancers.

Methods and analysis

Electronic searching of trastuzumab treatments for early breast cancer by titles and abstracts will be conducted for the period from inception to 16 June 2019 in PubMed, Cochrane Library, Embase and ClinicalTrils.gov, as well as the annual meetings of San Antonio Breast Cancer Symposium (SABCS), European Society of Medical Oncology (ESMO) and American Society of Clinical Oncology (ASCO) online archives. The outcomes of interest are overall survival, disease-free survival, acceptability, cardiotoxicities and grade 3 to 4 non-haematological toxicities. Two independent reviewers will screen and extract eligible data based on the inclusion and exclusion criteria, and then assess the risk of bias and evidence quality of individual studies using Cochrane Collaboration’s tool and Grades of Recommendation, Assessment, Development and Evaluation (GRADE). The heterogeneity, transitivity and inconsistency of NMA will be evaluated. In addition, we will perform subgroup and sensitivity analyses to assess the robustness and reliability of findings in our NMA.

Ethics and dissemination

Ethics approval is not required for our NMA. Findings from our NMA will be submitted as peer-reviewed journal manuscripts and international conference reports.

Trial registration number

CRD42019139109.
Is night-time light intensity associated with cardiovascular disease risk factors among adults in early-stage urbanisation in South India? A cross-sectional study of the Andhra Pradesh Children and Parents Study
Authors: Sorensen Tina Bonde , Wilson Robin , Gregson John , Shankar Bhavani , Dangour Alan D , Kinra Sanjay
Published: November 2020

Objectives

To explore associations of night-time light intensity (NTLI), a novel proxy for continuous urbanisation levels, with mean systolic blood pressure (SBP), body mass index (BMI), fasting serum low-density lipoprotein (LDL) and fasting plasma glucose (FPG), among adults in early-stage urbanisation in Telangana, South India.

Design

Cross-sectional analysis of the third wave of the Andhra Pradesh Children and Parents Study cohort.

Setting

28 villages representing a continuum of urbanisation levels, ranging from rural settlement to medium-sized town in Telangana, South India.

Participants

Data were available from 6944 participants, 6236 of whom were eligible after excluding pregnant women, participants younger than 18 years of age and participants missing data for age. Participants were excluded if they did not provide fasting blood samples, had implausible or missing outcome values, were medicated for hypertension or diabetes or had triglyceride levels invalidating derived LDL. The analysis included 5924 participants for BMI, 5752 participants for SBP, 5287 participants for LDL and 5328 participants for FPG.

Results

Increasing NTLI was positively associated with mean BMI, SBP and LDL but not FPG. Adjusted mean differences across the range of village-level NTLI were 1.0 kg/m2 (95% CI 0.01 to 1.9) for BMI; 4.2 mm Hg (95% CI 1.0 to 7.4) for SBP; 0.3 mmol/L (95% CI −0.01 to 0.7) for LDL; and −0.01 mmol/L (95% CI −0.4 to 0.4) for FPG. Associations of NTLI with BMI and SBP were stronger in older age groups.

Conclusion

The association of NTLI with cardiovascular disease (CVD) risk factors identify NTLI as a potentially important tool for exploring urbanisation-related health. Consistent associations of moderate increases in urbanisation levels with important CVD risk factors warrant prevention strategies to curb expected large public health impacts from continued and rapid urbanisation in India.
Diagnostic accuracy of an app-guided, self-administered test for influenza among individuals presenting to general practice with influenza-like illness: study protocol
Authors: Lyon Victoria , Zigman Suchsland Monica , Chilver Monique , Stocks Nigel , Lutz Barry , Su Philip , Cooper Shawna , Park Chunjong , Lavitt Libby Rose , Mariakakis Alex , Patel Shwetak , Graham Chelsey , Rieder Mark , LeRouge Cynthia , Thompson Matthew
Published: November 2020

Introduction

Diagnostic tests for influenza in Australia are currently only authorised for use in clinical settings. At-home diagnostic testing for influenza could reduce the need for patient contact with healthcare services, which potentially could contribute to symptomatic improvement and reduced spread of influenza. We aim to determine the accuracy of an app-guided nasal self-swab combined with a lateral flow immunoassay for influenza conducted by individuals with influenza-like illness (ILI).

Methods and analysis

Adults (≥18 years) presenting with ILI will be recruited by general practitioners (GP) participating in Australian Sentinel Practices Research Network. Eligible participants will have a nasal swab obtained by their GP for verification of influenza A/B status using reverse transcription polymerase chain reaction (RT-PCR) test at an accredited laboratory. Participants will receive an influenza test kit and will download an app that collects self-reported symptoms and influenza risk factors, then instructs them in obtaining a low-nasal self-swab, running a QuickVue influenza A+B lateral flow immunoassay (Quidel Corporation) and interpreting the results. Participants will also interpret an enhanced image of the test strip in the app. The primary outcome will be the accuracy of participants’ test interpretation compared with the laboratory RT-PCR reference standard. Secondary analyses will include accuracy of the enhanced test strip image, accuracy of an automatic test strip reader algorithm and validation of prediction rules for influenza based on self-reported symptoms. A post-test survey will be used to obtain participant feedback on self-test procedures.

Ethics and dissemination

The study was approved by the Human Research and Ethic Committee (HREC) at the University of Adelaide (H-2019-116). Protocol details and any amendments will be reported to https://www.tga.gov.au/. Results will be published in the peer-reviewed literature, and shared with stakeholders in the primary care and diagnostics communities.

Trial registration number

Australia New Zealand Clinical Trial Registry (U1111-1237-0688).
Characteristics and trends of clinical studies primarily sponsored by China in WHO primary registries between 2009 and 2018: a cross-sectional survey
Authors: Xu Yang , Dong Min , Liu Xuemei
Published: November 2020

Objectives

To analyse characteristics and developmental trends of clinical study registration primarily sponsored by China’s institutions during 2009–2018.

Setting

Registration information registered prior to 31 December 2018 was obtained from the International Clinical Trials Registry Platform (ICTRP) source registries, including Chinese Clinical Trial Registry, ClinicalTrials.gov, Australian New Zealand Clinical Trials Registry and International Standard Randomised Controlled Trial Number. Registration information on other ICTRP source registries was collected from the ICTRP.

Design

A cross-sectional analysis was performed. The studies sponsored by mainland China’s institutions (not including institutions in Hong Kong SAR, Macau SAR or Taiwan of China) as of 31 December 2018 were filtered. For duplicate registrations, only the records with the earliest registration date were included. Global registrations were summarised for comparison.

Results

A total of 32 557 China-sponsored studies and 478 261 global studies were included. The registered China-sponsored studies, increased from a cumulative number of 1333 in 2009 to 32 557 in 2018, were less likely to have industry involvement (14% vs 30%) and more likely to be registered prospectively (63% vs 45%) than the global registrations during 2009–2018. The top three most studied health conditions were lung cancer (4.2%), diabetes (3.8%) and ischaemic heart disease (3.2%). Depression and depressive disorders and chronic obstructive pulmonary disease (COPD) each represented 1.1% of registered China-sponsored studies. Phase 2 and phase 3 trials together accounted for 30%, notably lower than the global level (53%). The registered studies responding to an individual participant data (IPD) sharing plan had increased since 2016, but the proportions of studies indicating ‘yes’ were still at a low level and accounted for 5% of the registered China-sponsored studies and global registrations.

Conclusions

Clinical study registration activity in China has been substantial during 2009–2018. Some diseases with a high disease burden in China (depression and depressive disorders and COPD) were underrepresented by the proportion of registered studies. The accessibility of IPD merits improvement.
Using nudges to promote physical activity and to reduce sedentary behaviour in the workplace: a scoping review protocol
Authors: Forberger Sarah , Wichmann Frauke , Comito Chiara Nicoletta Nicoletta
Published: November 2020

Introduction

Physical inactivity and sedentary behaviour are associated with numerous health problems and increasing risks of premature morbidity and mortality. Workplace health promotion with a focus on increasing physical activity (PA) and reducing sedentary behaviour is of growing interest. The concept of choice architecture with the use of nudges is a promising approach to influence decision making regarding health behaviours. It can help to understand why people often fail to act in their best interest, to follow well-informed preferences or to achieve their set goals. Nudges, the way the choice is presented, can help to overcome these challenges by using the same habits, biases or boundaries to alter our decision-making in favour of the more preferred behaviour. Aims of the scoping review will be to analyse (a) to what extent the concept of choice architecture is used in workplace health promotion to promote PA and/or to reduce sedentary behaviour and (b) which instruments (nudges) are used to archive that.

Methods and analyses

Medline, PsychInfo, Web of Science and CINHAL will be searched from 2009 until June 2020. Applying a two-level screening process, title and abstracts will be screened according to a set of predetermined inclusion and exclusion criteria. Included articles will be screened a second time to determine the extent to which choice architecture has been used. Analyses for publication year, location, setting and target group will be provided. Interventions will be analysed presenting the instruments used, number of studies per instrument, combinations of instruments and alteration of the environment. Outcome measures and results will be reported as they occur.

Ethics and dissemination

Due to the nature of the scoping review, ethical concerns are minimal. No patient data will be included. Results are published in peer-review journals.
Repeat screening for syphilis in pregnancy as an alternative screening strategy in the UK: a cost-effectiveness analysis
Authors: Huntington Susie , Weston Georgie , Seedat Farah , Marshall John , Bailey Heather , Tebruegge Marc , Ahmed Imtyaz , Turner Katy , Adams Elisabeth
Published: November 2020

Objectives

To assess the cost-effectiveness of universal repeat screening for syphilis in late pregnancy, compared with the current strategy of single screening in early pregnancy with repeat screening offered only to high-risk women.

Design

A decision tree model was developed to assess the incremental costs and health benefits of the two screening strategies. The base case analysis considered short-term costs during the pregnancy and the initial weeks after delivery. Deterministic and probabilistic sensitivity analyses and scenario analyses were conducted to assess the robustness of the results.

Setting

UK antenatal screening programme.

Population

Hypothetical cohort of pregnant women who access antenatal care and receive a syphilis screen in 1 year.

Primary and secondary outcome measures

The primary outcome was the cost to avoid one case of congenital syphilis (CS). Secondary outcomes were the cost to avoid one case of intrauterine fetal demise (IUFD) or neonatal death and the number of women needing to be screened/treated to avoid one case of CS, IUFD or neonatal death. The cost per quality-adjusted life year gained was assessed in scenario analyses.

Results

Base case results indicated that for pregnant women in the UK (n=725 891), the repeat screening strategy would result in 5.5 fewer cases of CS (from 8.8 to 3.3), 0.1 fewer cases of neonatal death and 0.3 fewer cases of IUFD annually compared with the single screening strategy. This equates to an additional £1.8 million per case of CS prevented. When lifetime horizon was considered, the incremental cost-effectiveness ratio for the repeat screening strategy was £120 494.

Conclusions

Universal repeat screening for syphilis in pregnancy is unlikely to be cost-effective in the current UK setting where syphilis prevalence is low. Repeat screening may be cost-effective in countries with a higher syphilis incidence in pregnancy, particularly if the cost per screen is low.
Cost-effectiveness analysis and budget impact of rivaroxaban compared with dalteparin in patients with cancer at risk of recurrent venous thromboembolism
Authors: de Jong Lisa A , van der Velden Annette W G , Hulst Marinus van , Postma Maarten J
Published: November 2020

Objectives

In the ‘Comparison of an Oral Factor Xa Inhibitor With Low Molecular Weight Heparin in Patients With Cancer With Venous Thromboembolism’ (SELECT-D) trial, rivaroxaban showed relatively low venous thromboembolism (VTE) recurrence but higher bleeding compared with dalteparin in patients with cancer. We aim to calculate the cost-effectiveness and budget impact of rivaroxaban compared with dalteparin in patients with cancer at risk of recurrent VTE.

Setting

We built a Markov model to calculate the cost-effectiveness from a societal perspective over a 5-year time horizon for the Dutch healthcare setting.

Participants

A hypothetical cohort of 1000 cancer patients with VTE entered the model with baseline characteristics based on the SELECT-D trial.

Intervention

Six months of treatment with rivaroxaban (15 mg two times per day for first 3 weeks followed by 20 mg once daily) was compared with 6 months of treatment with dalteparin (200 IU/kg daily during month 1 followed by 150 IU/kg daily).

Primary and secondary outcome measures

The primary outcome of the cost-effectiveness analysis was the incremental cost-effectiveness ratio (ICER). The robustness of the model was evaluated in probabilistic and univariate sensitivity analyses. A budget impact analysis was performed to calculate the total annual financial consequences for a societal perspective in the Netherlands.

Results

In the base case and all scenarios, rivaroxaban were cost-saving while also slightly improving the patient’s health, resulting in economically dominant ICERs. In the probabilistic sensitivity analysis, 77.8% and 98.7% of the simulations showed rivaroxaban to be cost-saving and more effective for a 5-year and 6-month time horizon, respectively. Rivaroxaban can save up to €11 326 763 (CI €5 164 254 to €17 363 231) in approximately 8000 cancer patients with VTE per year compared with dalteparin based on a 1-year time horizon.

Conclusions

Treatment with rivaroxaban is economically dominant over dalteparin in patients with cancer at risk for recurrent VTE in the Netherlands. The use of rivaroxaban instead of dalteparin can save over €10 million per year, primarily driven by the difference in drug costs.
Impact of reimbursement rates on the length of stay in tertiary public hospitals: a retrospective cohort study in Shenzhen, China
Authors: Ning Jie , Liu Lingrui , Cherlin Emily , Peng Yarui , Yue Jingkai , Xiong Haoling , Tao Hongbing
Published: November 2020

Objective

To examine the association between reimbursement rates and the length of stay (LOS).

Design

A retrospective cohort study.

Setting

The study was conducted in Shenzhen, China by using health administrative database from 1 January 2015 to 31 December 2017.

Participants

6583 patients with acute myocardial infarction (AMI), 12 395 patients with pneumonia and 10 485 patients who received percutaneous coronary intervention (PCI) surgery.

Measures

The reimbursement rate was defined as one minus the ratio of out-of-pocket to the total expenditure, multiplied by 100%. The outcome of interest was the LOS. Multilevel negative binomial regression models were constructed to control for patient-level and hospital-level characteristics, and the marginal effect was reported when non-linear terms were available.

Results

Each additional unit of the reimbursement rate was associated with an average of an additional increase of 0.019 (95% CI, 0.015 to 0.023), 0.011 (95% CI, 0.009 to 0.014) and 0.013 (95% CI, 0.010 to 0.016) in the LOS for inpatients with AMI, pneumonia and PCI surgery, respectively. Adding the interaction term between the reimbursement rate and in-hospital survival, the average marginal effects for the deceased inpatients with AMI and PCI surgery were 0.044 (95% CI, 0.031 to 0.058) and 0.034 (95% CI, 0.017 to 0.051), respectively. However, there was no evidence that higher reimbursement rates prolonged the LOS of the patients who died of pneumonia (95% CI, −0.013 to 0.016).

Conclusions

The findings indicate that the higher the reimbursement rate, the longer the LOS; and implementing dynamic supervision and improving the service capabilities of primary healthcare providers may be an important strategy for reducing moral hazard in low-income and middle-income countries including China.
Assessing the efficacy and impact of a personalised smoking cessation intervention among type 2 diabetic smokers: study protocol for an open-label randomised controlled trial (DISCGO-RCT)
Authors: Clair Carole , Augsburger Aurélie , Birrer Priska , Locatelli Isabella , Schwarz Joelle , Greub Gilbert , Zanchi Anne , Jacot-Sadowski Isabelle , Puder Jardena J
Published: November 2020

Introduction

Few studies have assessed the efficacy of smoking cessation interventions in individuals with type 2 diabetes, but interventions adapted to the specific needs of this population are warranted. The aim of this study is to assess the efficacy of a smoking cessation intervention in a population of smokers with type 2 diabetes and to measure the metabolic impact of smoking cessation.

Methods and analysis

The study is an open-label, randomised control trial. Participants recruited from a sanitary region of Switzerland will be randomly allocated to either the intervention or the control arm. The intervention group will have four individual counselling sessions over 12 weeks. Trained research nurses will conduct the behavioural intervention, using motivational interviews and addressing diabetes and gender specificities. The control group will have one short counselling session at baseline and will be given written information on smoking cessation. Both groups will have a follow-up visit at 26 and 52 weeks. Demographic and medical data will be collected at baseline and follow-up, along with blood and urine samples. The primary study outcome is continuous smoking abstinence validated by expired-air carbon monoxide from week 12 to week 52. Secondary study outcomes are continuous and 7-day point prevalence smoking abstinence at 12 and 26 weeks; change in motivation to quit and cigarette consumption; and change in glycosylated haemoglobin levels, body weight, waist circumference and renal function after smoking cessation. In a subsample of 80 participants, change in stool microbiota from baseline will be measured at 3, 8 and 26 weeks after smoking cessation.

Ethics and dissemination

Ethical approval has been obtained by the competent ethics committee (Commission cantonale d’éthique de la recherche sur l’être humain, CER-VD 2017–00812). The results of the study will be disseminated through publications in peer-reviewed journals and conference presentations.

Trial registration numbers

ClinicalTrials.gov NCT03426423 and SNCTP000002762; Pre-results.