bluuebunny/crossref_metadata_2025 huggingface dataset:
A large multicentre, randomized, double‐blind, cross‐over study in healthy volunteers to compare pharmacokinetics, pharmacodynamics and safety of a pegfilgrastim biosimilar with its US‐ and EU‐reference biologics
Authors: Bellon Anne , Wang Jessie , Skerjanec Andrej , Velinova Maria , Dickerson Daniel , Sabet Ahad , Ngo Ly , O'Reilly Terry , Tomek Charles , Schussler Steven , Schier‐Mumzhiu Stefanie , Gattu Sreekanth , Koch Sven D. , Schelcher Celine , Dobreva Miryana , Boldea Anca , Nakov Roumen , Otto Gordon P.
Published: February 2020

Aims

Recombinant PEGylated human granulocyte colony‐stimulating factor (pegfilgrastim) is indicated for the reduction of chemotherapy‐induced neutropenia and prevention of febrile neutropenia. Biosimilar pegfilgrastim is expected to reduce the financial burden of this complication of chemotherapy. The aim of this study was to demonstrate biosimilarity between Sandoz biosimilar pegfilgrastim and its US‐ and EU‐approved reference biologics.

Methods

Phase I, randomized, double‐blind, single‐dose, 3‐period, 6‐sequence cross‐over, multicentre study to evaluate the pharmacokinetics, pharmacodynamics, safety and immunogenicity of Sandoz biosimilar pegfilgrastim with US‐ and EU‐references in healthy adults.

Results

Pharmacokinetic and pharmacodynamic similarity was demonstrated between the 3 biologics, as the 90% confidence interval for all primary pharmacokinetic and pharmacodynamic endpoint comparisons were contained within the predefined similarity margins of 0.80–1.25. Safety, immunogenicity and tolerability were also similar.

Conclusions

Sandoz biosimilar pegfilgrastim demonstrated pharmacokinetic and pharmacodynamic similarity to both US‐ and EU‐reference biologics. No meaningful differences in safety, local tolerability and immunogenicity were identified.
A 3‐year prospective study of a multidisciplinary early proactive therapeutic drug monitoring programme of infliximab treatments in inflammatory bowel disease
Authors: Sánchez‐Hernández José Germán , Rebollo Noemí , Martin‐Suarez Ana , Calvo M. Victoria , Muñoz Fernando
Published: February 2020

Aims

Therapeutic drug monitoring (TDM) of trough serum infliximab concentrations has been mainly used in case of loss of response in patients with inflammatory bowel disease (IBD). The aim of this study was to evaluate the effectiveness and safety of a multidisciplinary early proactive TDM (mep‐TDM) programme for dose adjustment.

Methods

A 3‐year prospective study was conducted based on a sample of 81 patients who started treatment and were subsequently subjected to mep‐TDM with the first control at week 14. Data of a historical control group of 72 patients treated with infliximab and managed with empirical dosing were included. Effectiveness variables were treatment failure, IBD‐related surgery and IBD‐related hospitalization. Safety variables were serious infusion reactions (SIRs) and adverse reactions. Cox regression was used for survival analysis.

Results

In the mep‐TDM study group, compared to the control group, there was a significant reduction in the risk of treatment failure (hazard ratio [HR]: 0.51; 95% confidence interval [CI]: 0.27–0.92; P = .037), IBD‐related surgery (HR: 0.14; 95% CI: 0.03–0.65; P = .012) and hospitalization (HR: 0.38; 95% CI: 0.17–0.87; P = .022). SIRs were lower in the mep‐TDM group (2.5% vs 10.4%; P < .050); the incidence of adverse reactions was similar (3.7% vs 3.9%; p > .999).

Conclusion

This study found that compared to empirical dosing, mep‐TDM is associated with improved efficacy and safety of infliximab therapy, reduced IBD‐related hospitalization and surgery and incidence of SIRs, and increasing long‐term durability of treatment effects.
IL‐11 in cardiac and renal fibrosis: Late to the party but a central player
Authors: Corden Benjamin , Adami Eleonora , Sweeney Mark , Schafer Sebastian , Cook Stuart A.
Published: February 2020

Fibrosis is a pathophysiological hallmark of cardiorenal disease. In the heart, fibrosis leads to contractile dysfunction and arrhythmias; in the kidney, it is the final common pathway for many diseases and predicts end‐stage renal failure. Despite this, there are currently no specific anti‐fibrotic treatments available for cardiac or renal disease. Recently and unexpectedly, IL‐11 was found to be of major importance for cardiorenal fibroblast activation and fibrosis. In mouse models, IL‐11 overexpression caused fibrosis of the heart and kidney while genetic deletion of Il11ra1 protected against fibrosis and preserved organ function. Neutralizing antibodies against IL‐11 or IL‐11RA have been developed that have anti‐fibrotic activity in human fibroblasts and protect against fibrosis in murine models of disease. While IL‐11 biology has been little studied and, we suggest, largely misunderstood, its autocrine activity in myofibroblasts appears non‐redundant for fibrosis, which offers new opportunities to better understand and potentially target cardiorenal fibrosis.
Designing mate choice experiments
Authors: Dougherty Liam R.
Published: February 2020

The important role that mate choice plays in the lives of animals is matched by the large and active research field dedicated to studying it. Researchers work on a wide range of species and behaviours, and so the experimental approaches used to measure animal mate choice are highly variable. Importantly, these differences are often not purely cosmetic; they can strongly influence the measurement of choice, for example by varying the behaviour of animals during tests, the aspects of choice actually measured, and statistical power. Consideration of these effects are important when comparing results among studies using different types of test, or when using laboratory results to predict animal behaviour in  natural populations. However, these effects have been underappreciated by the mate choice literature to date. I focus on five key experimental considerations that may influence choice: (i) should mating be allowed to occur, or should a proxy behavioural measure of preference be used instead? (ii) Should subjects be given a choice of options? (iii) Should each subject be tested more than once, either with the same or different stimuli? (iv) When given a choice, how many options should the subject choose between? (v) What form should the experimental stimuli take? I discuss the practical advantages and disadvantages of common experimental approaches, and how they may influence the measurement of mate choice in systematic ways. Different approaches often influence the ability of animals to perceive and compare stimuli presented during tests, or the perceived costs and benefits of being choosy. Given that variation in the design of mate choice experiments is likely unavoidable, I emphasise that there is no single ‘correct’ approach to measuring choice across species, although ecological relevance is crucial if the aim is to understand how choice acts in natural populations. I also highlight the need for quantitative estimates of the sizes of potentially important effects, without which we cannot make informed design decisions.
Prognostic value of serum soluble interleukin‐23 receptor and related T‐helper 17 cell cytokines in non‐small cell lung carcinoma
Authors: Liu Dan , Xing Shan , Wang Wan , Huang Xianzhang , Lin Haibiao , Chen Yonghe , Lan Kai , Chen Lin , Luo Fudong , Qin Sheng , Liang Rongliang , Bai Caiying , Xu Jianhua , Liu Wanli
Published: February 2020

The signaling of interleukin (IL)‐23 and its receptor (IL‐23R) play a crucial role in the development of cancers. However, the clinical significance of human serum soluble IL‐23R (sIL‐23R) and its relationship with IL‐23 are still not explored in non‐small cell lung cancer (NSCLC). In our study, sIL‐23R was first identified in the serum of NSCLC patients, but not in healthy controls, by proteomics. The IL‐23R mRNA and protein were upregulated in NSCLC cell lines and tissues tested by quantitative PCR, western blot analysis and immunohistochemistry. The levels of sIL‐23R, IL‐23, and IL‐17 in 195 NSCLC patients’ serum were determined by ELISA, and high levels of sIL‐23R were significantly associated with advanced N stage (P = .039), clinical stage (P = .007), and poor 5‐year survival rate. In vitro, sIL‐23R was shown binding to IL‐23 and the balance could affect patients’ N and T stage, overall survival, and downstream cytokine IL‐17 in a potential antagonistic relationship. Although sIL‐23R, IL‐23, and IL‐17 were all associated with poor prognosis, only the sIL‐23R/IL‐23 ratio (hazard ratio, 1.945; 95% confidence interval, 1.147‐3.299; P = .014) was found to be an independent factor for prognosis. Therefore, we identified fragments of soluble cytokine receptor of IL‐23R with affinity ability to its natural ligand IL‐23 in NSCLC patients’ serum. The balance between the 2 antagonists can work as a potential prognostic serum marker.
Linking children's social care data to information about their care proceedings to understand the use of care proceedings and their effects on parents, children and local authorities.
Authors: Masson Judith , Garside Ludivine , Jenney Sean
Published: February 2020

Care proceedings are the most powerful child protection intervention; local authorities make applications for over 20,000 children each year in England and Wales. The Department for Education holds two administrative databases of children who receive services, for children looked after and children in need. These databases do not record the use of care proceedings. Data linkage is a powerful tool for revealing patterns not visible from a single data set; the Outcomes for children before and after care proceedings reform study linked these administrative records with a research database of care proceedings to examine children's care and service journeys associated with care proceedings. The researchers also devised a simplified method for use by local authorities with their own records and tested this with North Yorkshire County Council. Analysis of the linked data reveals how care proceedings are used and the impact of care proceedings on care demand. It provides the basis for analysis of cohorts of children subject to proceedings and feedback to social workers, children's guardians, and the judges and lawyers on their decisions and children's outcomes.
The role of the cancer testis antigen PRAME in tumorigenesis and immunotherapy in human cancer
Authors: Xu Yichi , Zou Ruanmin , Wang Jing , Wang Zhi‐wei , Zhu Xueqiong
Published: February 2020

Preferentially expressed antigen in melanoma (PRAME), which belongs to the cancer/testis antigen (CTA) gene family, plays a pivotal role in multiple cellular processes and immunotherapy response in human cancers. PRAME is highly expressed in different types of cancers and is involved in cell proliferation, apoptosis, differentiation and metastasis as well as the outcomes of patients with cancer. In this review article, we discuss the potential roles and physiological functions of PRAME in various types of cancers. Moreover, this review highlights immunotherapeutic strategies that target PRAME in human malignancies. Therefore, the modulation of PRAME might be useful for the treatment of patients with cancer.
Primary cutaneous osteosarcoma of the scalp in an immunosuppressed individual: A case report and review of the literature
Authors: Hunjan Manrup Kaur , Brockley Julia , Zanetto Ulises , Maheshwari M.B. , Díaz Camilo
Published: February 2020

We report a case of a 76‐year‐old man presenting with a 12‐month history of a solitary lesion on his scalp. The histopathology was consistent with a grade 2/3 osteosarcoma extending to the subcutis. Full‐body imaging excluded any involvement of the underlying bony tissue or solid organ malignancy, thus a diagnosis of primary cutaneous osteosarcoma (PCO) was made. Given the exceedingly rare nature of PCO, we discuss the clinico‐pathological features of this case and those previously reported in the literature.
Fixed‐dose combination of empagliflozin and linagliptin for the treatment of patients with type 2 diabetes mellitus: A systematic review and meta‐analysis
Authors: Katsiki Niki , Ofori‐Asenso Richard , Ferrannini Ele , Mazidi Mohsen
Published: February 2020

The present meta‐analysis evaluated the efficacy and safety of empagliflozin + linagliptin combination compared with either monotherapy [n=6 randomized controlled trials; 2857 adults with type 2 diabetes (T2DM) on diet + exercise ± metformin; 39.7% women; mean age: 54.6–59.9 years]. The combination of empagliflozin 10 mg + linagliptin 5 mg led to significantly greater reductions in glycated haemoglobin (HbA1c) compared with either drug alone over 24 weeks: weighted mean difference [WMD; −0.72%, 95% confidence interval (CI): −1.04, −0.40], and fasting plasma glucose (−1.60 mmol/L 95% CI: −2.21, −1.00). Similar results were observed when empagliflozin 25 mg + linagliptin 5 mg was compared with linagliptin 5 mg monotherapy or with empagliflozin 10 or 25 mg monotherapy. Patients with T2DM treated with the drug combination had more than three times higher likelihood of achieving HbA1c <7% than those on either monotherapy. Weight reduction was significantly greater in the combination group only when compared with linagliptin monotherapy. Safety profile was similar between combination treatment and monotherapies. Overall, the empagliflozin + linagliptin combination had superior efficacy and similar safety in achieving euglycaemia compared with either monotherapy. This combination, administered once daily, has the potential to reduce regimen complexity, enhance adherence and improve outcomes in clinical practice.
Collaboration and innovation: An empirical study of Indian technological enterprises
Authors: Heaton Chris , Kolluru Srinivas , Mukhopadhaya Pundarik
Published: February 2020

In 2010, the Indian government declared 2010–2020 to be the ‘Decade of Innovation’ and established the State Innovation Councils and Sectoral Innovation Councils to encourage and facilitate innovation by technological firms. In this paper, we study the relationship between collaboration and innovation in a cross‐section of Indian firms, paying particular attention to the impact of the innovation councils. Our results suggest that domestic collaborations have an important impact on firm innovation, as do the innovation councils, but that the impact of the councils is less for firms that collaborate.
First report of Rhytisma filamentosum causing tar‐spot disease on Salix koriyanagi
Authors: Jung Bok Nam , Park Ji‐Hyun , Shin Hyeon‐Dong
Published: February 2020

The occurrence of previously unknown tar‐spot disease on Salix koriyanagi was observed during surveys for forest disease outbreaks in Korea. The fungus associated with tar‐spot disease was identified as Rhytisma filamentosum based on morphological characteristics of the fungus and molecular sequencing of the ITS and 28S rDNA regions of two samples. To our knowledge, this is the first report of R. filamentosum on S. koriyanagi from Korea, following its first discovery on Salix integra in Japan.
Treatment initiation decisions in newly diagnosed epilepsy–A longitudinal cohort study
Authors: Sharma Sameer , Chen Zhibin , Rychkova Maria , Dunne John , Lee Judy , Kalilani Linda , Lawn Nicholas , Kwan Patrick
Published: February 2020

Objective

To examine the factors and reasons influencing treatment initiation decisions in patients with newly diagnosed epilepsy.

Methods

We assessed antiseizure medication initiation decisions in adults with newly diagnosed epilepsy seen at first seizure clinics in Western Australia between 1999 and 2016 and followed to 2018.

Results

Of 610 patients (median age 40 years, 61.0% male), 426 (69.8%) were diagnosed after two or more seizures and 184 (30.2%) after a single seizure with risk factors for recurrence. Treatment was commenced in 427 patients (70.0%) at diagnosis, 112 (18.4%) during follow‐up, mostly after further seizures, whereas 71 (11.6%) remained untreated at last follow‐up. Elders (≥65 years, odds ratio [OR] = 3.06, 95% confidence interval [CI]: 1.62‐5.80), more seizures (OR = 3.48, 95% CI: 2.03‐5.96), and epileptogenic lesions on neuroimaging (OR = 2.15, 95% CI: 1.26‐3.68) had a higher likelihood of treatment at diagnosis. Patients with less than one seizure per year within the preceding year (OR = 0.40, 95% CI: 0.21‐0.73) and of higher socioeconomic status (OR = 0.985, 95% CI: 0.977‐0.994) were less likely to be treated. For 93 patients (15.2%), treatment was not recommended at diagnosis, most commonly because only a single seizure had occurred. Ninety patients (14.8%) declined recommended treatment, mostly because they were unconvinced of the need for treatment or the diagnosis.

Significance

Thirty percent of adults with newly diagnosed epilepsy were not immediately treated. Treatment initiation in this real‐world cohort was influenced by age, number of seizures prior to diagnosis, imaging findings, patient preferences, and socioeconomic status.
Scaling and fractality in subcritical fatigue crack growth: Crack‐size effects on Paris' law and fatigue threshold
Authors: Carpinteri Alberto , Montagnoli Francesco
Published: February 2020

The present contribution investigates the crack‐size effects on Paris' law in accordance with dimensional analysis and intermediate asymptotics theory, which makes it possible to obtain a generalised equation able to provide an interpretation to the various empirical power‐laws available in the Literature. Subsequently, within the framework of fractal geometry, scaling laws are determined for the coordinates of the limit‐points of Paris' curve so that a theoretical explanation is provided to the so‐called short cracks problem. Eventually, the proposed models are compared with experimental data available in the literature which seem to confirm the advantage of applying a fractal model to the fatigue problem.
Current status of gerodontology curriculum in India and other parts of the world: A narrative review
Authors: Shigli Kamal , Nayak Sushma S. , Jirge Vasanti , Srinagesh Jyotsna , Murthy Varsha , Gali Sivaranjani
Published: February 2020

Background

The current rise in the world's geriatric population has placed additional demands on dental professionals, as the management of geriatric patients requires distinct competencies.

Aim

To review and perform a content analysis of the gerodontology undergraduate curriculum worldwide.

Data sources

A search was carried out in PubMed, Web of Science, ERIC and EMBASE databases for the period—July 2008 till May 2019, using MeSH terms. A search for websites of Indian universities was also done, and undergraduate curricula were screened.

Study eligibility criteria

The study included articles related to the undergraduate curriculum, which contained training in geriatric dentistry. Articles in foreign languages and those related to dental hygienists were excluded.

Results

A total of 218 articles were obtained, of which 19 met the inclusion criteria. A total of 301 colleges taught gerodontology. Amongst them, 50 colleges had a gerodontology department. Clinical training and outreach experience were provided in 175 and 73 colleges, respectively. There are no reports on the status of gerodontology in Asian countries (excluding Japan). In India, gerodontology is not taught as a separate subject. However, few gerodontology‐related topics are covered in clinical subjects.

Conclusions

There seems to be a wide variation in the content of gerodontology curriculum taught worldwide. Other than the European and American regions, gerodontology is yet to develop in other parts of the world. In India, a robust training programme is required to address the lack of dental care providers for the geriatric population using guidelines established by ECG and ADEA.
Impact of dementia on quality of death among cancer patients: An observational study of home palliative care users
Authors: Hirooka Kayo , Nakanishi Miharu , Fukahori Hiroki , Nishida Atsushi
Published: February 2020

Aim

The number of cancer patients with dementia has increased markedly in accordance with aging societies. Cancer patients might receive palliative and end‐of‐life care to maintain their quality of life; however, the impact of dementia on the quality of death is unexamined in this population. Consequently, we explored the impact of dementia on the quality of death among cancer patients.

Methods

Home palliative care staff members completed questionnaires regarding cancer patients’ (n = 508) cognitive status, cancer‐related symptoms and quality of death using the good death inventory. Hierarchical regression analyses were carried out for the entire sample and for stratified groups based on the presence of dementia.

Results

Of the 508 patients, 156 (30.7%) had dementia. Hierarchical regression analyses revealed that greater quality of death was associated with not having dementia (P < 0.001). Stratified analyses showed that dying at home was related to greater quality of death both in patients with and without dementia. The presence of a primary family caregiver was associated with greater quality of death only in patients with dementia (P < 0.001).

Conclusions

Cancer patients with dementia were less likely to achieve a good death than those without. Our results suggest the importance of enhancing end‐of‐life care discussions with patients and their families, along with developing specific support strategies to enhance the decision‐making of cancer patients with dementia and their family members. Geriatr Gerontol Int 2020; 20: 354–359.
Connecting care chains and care diamonds: the elderly care skills regime in Singapore
Authors: ORTIGA YASMIN Y. , WEE KELLYNN , YEOH BRENDA S. A.
Published: February 2020

Research on the globalization of care work often faces the persistent challenge of building meaningful connections between the movement of care labour at a global scale and place‐based frameworks of care access and delivery. In addressing this gap in this article, we propose to take a closer look at how the care‐migration nexus produces ‘ideal’ care workers through a skills regime. Based on the case of elderly care in Singapore, in this article, we demonstrate how state institutions and private agencies attempts to fill local labour needs by producing care workers among both Singapore citizens and migrant women. This leads to contradictory strategies associated with lowering barriers for citizens to enter the elderly care industry, while raising standards and increasing pre‐training demands for migrant domestic workers to perform more ‘professional’ care work within the household. We conclude with a discussion of how these strategies can be understood as a process of ‘filtering’.
Sulfur Hexafluoride and Potassium Bromide as Groundwater Tracers for Managed Aquifer Recharge
Authors: Gerenday Sarah P. , Clark Jordan F. , Hansen Jeffrey , Fischer Ida , Koreny John
Published: February 2020

Sulfur hexafluoride (SF6) is an established tracer for use in managed aquifer recharge projects. SF6 exsolves from groundwater when it encounters trapped air according to Henry's law. This results in its retardation relative to groundwater flow, which can help determine porous media saturation and flow dynamics. SF6 and the conservative, nonpartitioning tracer, bromide (Br− added as KBr), were introduced to recharge water infiltrated into stacked glacial aquifers in Thurston County, Washington, providing the opportunity to observe SF6 partitioning. Br−, which is assumed to travel at the same velocity as the groundwater, precedes SF6 at most monitoring wells (MWs). Average groundwater velocity in the unconfined aquifer in the study area ranges from 3.9 to 40 m/d, except in the southwestern corner where it is slower. SF6 in the shallow aquifer exhibits an average retardation factor of 2.5 ± 3.8, suggesting an air‐to‐water ratio on the order of 10−3 to 10−2 in the pore space. Notable differences in tracer arrival times at adjacent wells indicate very heterogeneous conductivity. One MW exhibits double peaks in concentrations of both tracers with different degrees of retardation for the first and second peaks. This suggests multiple flowpaths to the well with variable saturation. The confining layer between the upper two aquifers appears to allow intermittent connection between aquifers but serves as an aquitard in most areas. This study demonstrates the utility of SF6 partitioning for evaluating hydrologic conditions at prospective recharge sites.
Reducing salt content in beef frankfurter by edible coating to achieve inhomogeneous salt distribution
Authors: Xiong Yun , Deng Borui , Warner Robyn Dorothy , Fang Zhongxiang
Published: February 2020

High dietary salt (NaCl) intake is a global health concern which leads to various chronic diseases; hence, the reduction of salt content in foods has been a high demand in the food industry. Inhomogeneous salt distribution is a promising strategy for salt reduction. This study investigated the effect of inhomogeneous salt distribution using salt edible coating on the physiochemical and sensory attributes of beef frankfurter sausages. Results demonstrated that this method significantly reduced the salt content in frankfurter sausages by 60–81% without affecting the consumers’ perception of saltiness intensity. Among the coated samples, 7.5% and 10% salt coating samples showed the best performance on the product quality. However, the problems associated with high cooking loss and hard texture of the salt‐coated sausages need to be further addressed. This research has potentially developed a new method for manufacture of salt‐reduced food.
The Clinical Learning Environment, Supervision and the Nurse Teacher Evaluation Scale: Turkish Version
Authors: Iyigun Emine , Tastan Sevinc , Ayhan Hatice , Pazar Berrin , Tekin Yasemin Eda , Coskun Halise , Saarikoski Mikko
Published: February 2020

Aim

The aim of this study is to adapt the Clinical Learning Environment, Supervision and Nurse Teacher Evaluation Scale to the Turkish language and culture.

Methods

This psychometric test was conducted in a nursing school in Ankara, Turkey, from April to June 2014. Convenience sampling was used. The sample of this study was 190 third‐ and fourth‐year nursing students. The items of the scale were evaluated by Pearson correlation coefficient for correlation‐based item analysis. Cronbach's alpha, test and retest analysis were used to measure reliability. Exploratory factor analysis and correlation analysis were performed to determine validity. Principal component analysis was used to analyze factor.

Results

The subscales' Cronbach's alpha values were varied between .760 and .933. A positive relationship was found between tests and retests points of the subscales (P < .05). Five factors were identified in the exploratory factor analysis. There was a meaningful correlation between subscale points of the Clinical Learning Environment, Supervision and Nurse Teacher Evaluation Scale and the Clinical Learning Environment Scale (P < .05).

Conclusion

The Turkish version of the Clinical Learning Environment, Supervision and Nurse Teacher Evaluation Scale was validated and a reliable measurement tool. It can be used to evaluate clinical nursing education in Turkey.
Pediatric obesity treatment, self‐esteem, and body image: A systematic review with meta‐analysis
Authors: Gow Megan L. , Tee Melissa S.Y. , Garnett Sarah P. , Baur Louise A. , Aldwell Katharine , Thomas Sarah , Lister Natalie B. , Paxton Susan J. , Jebeile Hiba
Published: February 2020

Background

Pediatric obesity impacts on multiple domains of psychological health, including self‐esteem and body image.

Objective

To determine the effect of multicomponent pediatric obesity treatment interventions on self‐esteem and body image.

Methods

A systematic search of published literature up to June 2019 was undertaken using electronic databases MEDLINE, EMBASE, Cochrane Library, and PsychINFO. Eligible studies implemented an obesity treatment intervention, including a dietary and physical activity component with/without a behavioral component, in children and adolescents with overweight/obesity, and assessed self‐esteem and/or body image. Data were extracted by one reviewer and cross‐checked. Meta‐analysis was used to combine outcome data and moderator analysis conducted to identify intervention characteristics influencing outcomes.

Results

64 studies were identified. Meta‐analysis of 49 studies (n = 10471) indicated that pediatric obesity treatment results in increased self‐esteem postintervention (standardized mean difference, [SE] 0.34 [0.03], P < .001, I2 87%), maintained at follow‐up (0.35 [0.05] P < .001, I2 79%, 17 studies). Similarly, meta‐analysis of 40 studies (n = 2729) indicated improvements in body image postintervention (0.40 [0.03], P < .001, I2 73%), maintained at follow‐up (0.41 [0.08], P < .001, I2 89%, 16 studies).

Conclusions

Pediatric obesity treatment improves self‐esteem and body image in the short and medium term. These findings may underpin improvements in other psychological outcomes.
The effects of age on clinical characteristics, hospitalization and mortality of patients with influenza‐related illness at a tertiary care centre in Malaysia
Authors: Wong Pui Li , Sii Hoe Leong , P'ng Chun Keat , Ee Soon Sean , Yong Oong Xiang , Ng Kim Tien , Hanafi Nik Sherina , Tee Kok Keng , Tan Maw Pin
Published: February 2020

Background

Age is an established risk factor for poor outcomes in individuals with influenza‐related illness, and data on its influence on clinical presentations and outcomes in the South‐East Asian settings are scarce. The aim of this study was to determine the above among adults with influenza‐related upper respiratory tract infection at a teaching hospital in Malaysia.

Methods

A retrospective case‐note analysis was conducted on a cohort of 3935 patients attending primary care at the University Malaya Medical Centre, Malaysia from February 2012 till May 2014 with URTI symptoms. Demographics, clinical characteristics, medical and vaccination history were obtained from electronic medical records, and mortality data from the National Registration Department. Comparisons were made between those aged <25, ≥25 to <65 and ≥65 years.

Results

470 (11.9%) had PCR‐confirmed influenza virus infection. Six (1.3%) received prior influenza vaccination. Those aged ≥65 years were more likely to have ≥2 comorbidities (P < .001) and were less likely to present with fever (P = .004). One‐third of those aged ≥65 years experienced hospitalization, intensive care admission or death within a year compared to 10% in the ≥25 to <65 years. Age ≥65 years was an independent predictor of hospitalization and death (OR = 9.97; 95% CI = 3.11‐31.93) compared to those aged <25 years.

Conclusion

Older patients in our cohort were more likely to have comorbidities and present with atypical features, with older age being an independent predictor of poor health outcomes. Our findings will now inform future health policies on older persons and economic modelling of adult vaccination programmes.
Toward unified molecular surveillance of RSV: A proposal for genotype definition
Authors: Goya Stephanie , Galiano Mónica , Nauwelaers Inne , Trento Alfonsina , Openshaw Peter J. , Mistchenko Alicia S. , Zambon Maria , Viegas Mariana
Published: February 2020

Background

Human respiratory syncytial virus (RSV) is classified into antigenic subgroups A and B. Thirteen genotypes have been defined for RSV‐A and 20 for RSV‐B, without any consensus on genotype definition.

Methods

We evaluated clustering of RSV sequences published in GenBank until February 2018 to define genotypes by using maximum likelihood and Bayesian phylogenetic analyses and average p‐distances.

Results

We compared the patterns of sequence clustering of complete genomes; the three surface glycoproteins genes (SH, G, and F, single and concatenated); the ectodomain and the 2nd hypervariable region of G gene. Although complete genome analysis achieved the best resolution, the F, G, and G‐ectodomain phylogenies showed similar topologies with statistical support comparable to complete genome. Based on the widespread geographic representation and large number of available G‐ectodomain sequences, this region was chosen as the minimum region suitable for RSV genotyping. A genotype was defined as a monophyletic cluster of sequences with high statistical support (≥80% bootstrap and ≥0.8 posterior probability), with an intragenotype p‐distance ≤0.03 for both subgroups and an intergenotype p‐distance ≥0.09 for RSV‐A and ≥0.05 for RSV‐B. In this work, the number of genotypes was reduced from 13 to three for RSV‐A (GA1‐GA3) and from 20 to seven for RSV‐B (GB1‐GB7). Within these, two additional levels of classification were defined: subgenotypes and lineages. Signature amino acid substitutions to complement this classification were also identified.

Conclusions

We propose an objective protocol for RSV genotyping suitable for adoption as an international standard to support the global expansion of RSV molecular surveillance.
Annual Research Review: Defining and treating pediatric treatment‐resistant depression
Authors: Dwyer Jennifer B. , Stringaris Argyris , Brent David A. , Bloch Michael H.
Published: February 2020

Background

Adolescent major depressive disorder (MDD) is a significant health problem, associated with substantial morbidity, cost, and mortality. Depression is a significant risk factor for suicide, which is now the second leading cause of death in young people. Up to twenty per cent of adolescents will experience MDD before adulthood, and while a substantial proportion will improve with standard‐of‐care treatments (psychotherapy and medication), roughly one third will not.

Methods

Here, we have reviewed the literature in order to discuss the concept of treatment‐resistant depression (TRD) in adolescence, examine risk factors, diagnostic difficulties, and challenges in evaluating symptom improvement, and providing guidance on how to define adequate medication and psychotherapy treatment trials.

Results

We propose a staging model for adolescent TRD and review the treatment literature. The evidence base for first‐ and second‐line treatments primarily derives from four large pediatric clinical trials (TADS, TORDIA, ADAPT, and IMPACT). After two medications and a trial of evidence‐based psychotherapy have failed to alleviate depressive symptoms, the evidence becomes quite thin for subsequent treatments. Here, we review the evidence for the effectiveness of medication switches, medication augmentation, psychotherapy augmentation, and interventional treatments (i.e., transcranial magnetic stimulation, electroconvulsive therapy, and ketamine) for adolescent TRD. Comparisons are drawn to the adult TRD literature, and areas for future pediatric depression research are highlighted.

Conclusions

As evidence is limited for treatments in this population, a careful consideration of the known risks and side effects of escalated treatments (e.g., mood stabilizers and atypical antipsychotics) is warranted and weighed against potential, but often untested, benefits.
Risk and population attributable fraction of metabolic syndrome and impaired fasting glucose for the incidence of type 2 diabetes mellitus among middle‐aged Japanese individuals: Aichi Worker’s Cohort Study
Authors: Kaneko Kayo , Yatsuya Hiroshi , Li Yuanying , Uemura Mayu , Chiang Chifa , Hirakawa Yoshihisa , Ota Atsuhiko , Tamakoshi Koji , Aoyama Atsuko
Published: February 2020

Aims/Introduction

The Japanese government started a nationwide screening program for metabolic syndrome (MetS) to prevent cardiovascular diseases and diabetes in 2008. Although impaired fasting glucose (IFG) is a strong predictor for type 2 diabetes mellitus, the program does not follow up IFG in non‐MetS individuals. This study aimed to examine the risk and the population attributable fraction (PAF) of MetS and IFG for incidence of type 2 diabetes mellitus.

Materials and Methods

Japanese workers (3,417 men and 714 women) aged 40–64 years without a history of diabetes were prospectively followed. MetS was defined as either abdominal obesity plus two or more metabolic risk factors, or being overweight in the case of normal waist circumference plus three or more metabolic risk factors. IFG was defined as fasting blood glucose 100–125 mg/dL.

Results

During a mean 6.3 years, 240 type 2 diabetes mellitus cases were identified. Compared with those without MetS and IFG, the multivariable‐adjusted hazard ratios (95% confidence interval) of non‐MetS individuals with IFG, MetS individuals without IFG and MetS individuals with IFG for type 2 diabetes mellitus were 4.9 (3.4–7.1), 2.4 (1.6–3.5) and 8.3 (5.9–11.5), respectively. The corresponding PAFs for type 2 diabetes mellitus incidence were 15.6, 9.1 and 29.7%, respectively.

Conclusions

IFG represented a higher risk and PAF than MetS for type 2 diabetes mellitus incidence in middle‐aged Japanese individuals. The coexistence of MetS and IFG showed the highest risk and PAF for type 2 diabetes mellitus incidence. The current Japanese MetS screening program should be reconsidered to follow up non‐MetS individuals with IFG.
The role of the interleukin‐23/Th17 pathway in cardiometabolic comorbidity associated with psoriasis
Authors: Egeberg A. , Gisondi P. , Carrascosa J.M. , Warren R.B. , Mrowietz U.
Published: February 2020

Alterations in the innate and adaptive immunity underpin psoriasis pathophysiology, with the Th17 cells subset now recognized as the fundamental cells in the key controlling pathway involved in its pathogenesis. Since psoriasis is a systemic disease with important comorbidity, further knowledge on the interleukin (IL)‐23/Th17 axis led to the hypothesis that there may be shared pathogenic pathways between primary skin disease and comorbidity. Psoriasis has been identified as a risk factor for cardiovascular and metabolic disease, and increasing evidence gives support to this epidemiological observation from the clinical‐pathologically field. As an example, increased levels ofIL‐23 andIL‐23R have been found in human atherosclerotic plaque, and levels correlated with symptom duration and mortality. Also, upregulation ofIL‐23/IL‐17 seems to play an important role in both myocardial damage and stroke, with interesting reports on deleterious effect neutralization after administration of related anti‐bodies in both associated conditions. In diabetic patients, increased levels ofIL‐23/IL‐17 have also been observed and available data support a synergistic role ofIL‐23/IL‐17 in β‐cells damage. In obesity, signs of an expansion of Th17 subset in adipose tissue have been reported, as well as elevated concentrations ofIL‐23 in obese patients. In non‐alcoholic fatty liver disease, closely related to metabolic syndrome, but also in other mentioned cardiometabolic disorders, a predominance ofIL‐23 and other related pro‐inflammatory factors has been identified as participating in their pathogenesis. Thus, the involvement of theIL‐23/Th17 axis in these shared psoriasis‐cardiometabolic pathogenic mechanisms is reviewed and discussed in the light of the existing preclinical and clinical evidence, including that from comorbid psoriasis patients.
ISLAMIC BANKING, COSTLY RELIGIOSITY, AND COMPETITION
Authors: Azmat Saad , Azad A. S. M. Sohel , Bhatti M. Ishaq , Ghaffar Hamza
Published: February 2020

In this article we explain how Islamic banks (IBs) maximize profitability in the presence of costly religiosity. Because of strong competition between IBs and conventional banks (CBs), a unique equilibrium emerges that affects the IB pricing structure. We propose a new model that identifies the optimal rate on the asset and liability sides of IBs. It shows that the financial products offered by IBs are not an exogenous function of religiosity; instead, they are endogenously determined by the nature of market forces in which IBs are operating. We show that in the presence of costly religiosity and competition, the rates of both converge. Moreover, the competitive pricing mechanism induces IBs to structure their asset‐ and liability‐side financial products (particularly Murabaha) with a risk profile similar to that of the CB loan system. This article empirically supports the theoretical propositions by using data from 17 Muslim majority countries where both IBs and CBs coexist from 2000 to 2015. We find that, holding other factors of bank returns constant, competition significantly affects IB asset‐ and liability‐side returns. The analysis also reveals that because of increasing competition between IBs and CBs, the market power of IBs has significantly declined over time.
Role of SSH1 in colorectal cancer prognosis and tumor progression
Authors: Song Xiangping , Xie Di , Xia Xiao , Tan Fengbo , Pei Qian , Li Yuqiang , Zhou Zhongyi , Zhou Yuan , Li Chenglong , Wang Kangtao , Pei Haiping
Published: February 2020

Background and Aim

Slingshot 1 protein (SSH1) plays a critical role in cytoskeleton dynamic regulation. Increasing evidence suggest that SSH1 expression is upregulated in several cancers and relates to tumor progression and drug resistance. Here, we evaluated the role of SSH1 in colorectal cancer (CRC) development and its prognostic value in patients with CRC.

Methods

SSH1 expression was examined by quantitative real‐time polymerase chain reaction, western blot analysis, or immunohistochemistry. The association between SSH1 expression and clinical characteristics and prognosis was evaluated. Stable SSH1 knockdown cells were used for in vitro assays and xenograft models. Correlation between SSH1 expression and epithelial–mesenchymal transition (EMT) was analyzed by western blot and online data analysis.

Results

SSH1 expression was upregulated in cancer tissue compared with paired non‐cancerous tissue in patients with CRC. SSH1 expression level in CRC tissue was associated with tumor stage, lymph node metastasis, and correlated with poor prognosis as indicated by univariate and multivariate analyses. In vitro, loss of SSH1 impaired colony formation, migration, and invasion of CRC cells. In vivo data suggest that SSH1 could promote the progression and metastasis of CRC. Interestingly, E‐cadherin, ZEB1, and Snail, which are markers of EMT, had a significant expression correlation with SSH1.

Conclusions

SSH1 expression is associated with CRC progression and predicts poor prognosis. SSH1 may promote CRC tumor progression by regulating EMT.
The development of consensus‐based guidelines for dietetic practice in nasogastric tube feeding under restraint for patients with anorexia nervosa using a modified Delphi process
Authors: Fuller S. J. , Philpot U. ,   Working Group
Published: February 2020

Introduction

Nasogastric tube feeding against a person's will, under restraint, can be a lifesaving intervention for patients with severe anorexia nervosa. Dietetic guidelines have been developed to support dietitians in this specialised area.

Methods

A modified Delphi process was used in the development of the guidelines; stage 1, initial stakeholders created a draft; stage 2, creation of the working group; stage 3, comments and feedback on draft; stage 4, final draft agreed; stage 5, external review from Psychiatrists, patients and carers; stage 6, endorsement. Specialist mental health dietitians working in both adult and Child and Adolescent Mental Health Services (CAMHS) across four countries contributed to the development of the consensus guidelines.

Results

New guidance is outlined specifically for NGT feeding under restraint, which details the process, rate and volume of feed to comply with lawful guidance.

Conclusions

Clinical guidelines were developed for dietitians treating patients with anorexia nervosa, using a modified Delphi process, incorporating both expert opinion and all available evidence. The guidance provides new information to dietitians and clinicians in how to enterally feed patients under restraint where none previously existed.
Report on the impact of a service improvement programme in a well‐established radiologically inserted gastrostomy service
Authors: Carvalho F. , Wiseman T.
Published: February 2020

Background

The present study aimed to evaluate whether the implementation of a service improvement programme improved the occurrence of radiologically inserted gastrostomy (RIG) tube displacements, post‐insertion.

Methods

A retrospective observational study of cancer patients was conducted over a 2‐year period divided into two time points. Eighty‐two RIG insertions were audited retrospectively; 42 in Time 1 and 40 in Time 2.

Results

Some 70% (n = 57) of patients had head and neck (H&N) malignancy, 24% (n = 20) had gastrointestinal cancer and 6% (n = 5) had a variety of other malignancies. Following the implementation of the service improvement programme, the number of RIG tube displacements almost halved from nine (21%) to five (12%).

Conclusions

The present study offers persuasive evidence indicating that the implemented service improvement programme improved patient care; however, further research incorporating a more robust evaluation is necessary. People with advanced disease are living longer and so there is a need to maintain good nutritional support. This innovation offers the potential to enhance patients' quality of care and minimise complications.
Anxiety and threat‐related attentional biases in adolescents with fragile X syndrome
Authors: Kelleher B. L. , Hogan A. L. , Ezell J. , Caravella K. , Schmidt J. , Wang Q. , Roberts J. E.
Published: February 2020

Background

Fragile X syndrome (FXS) is a single‐gene disorder highly associated with anxiety; however, measuring anxiety symptoms in FXS and other neurogenetic syndromes is challenged by common limitations in language, self‐awareness and cognitive skills required for many traditional assessment tasks. Prior studies have documented group‐level differences in threat‐related attentional biases, assessed via eye tracking, in FXS and non‐FXS groups. The present study built on this work to test whether attentional biases correspond to clinical features of anxiety among adolescents and young adults with FXS.

Methods

Participants included 21 male adolescents with FXS ages 15–20 years who completed an adapted eye‐tracking task that measured attentional bias towards fearful faces of varied emotional intensity.

Results

Among participants without anxiety disorders, attentional bias towards fear increased across age, similar to non‐FXS paediatric anxiety samples. In contrast, participants with anxiety disorders exhibited greater stability in fear‐related attentional biases across age. Across analyses, subtle fear stimuli were more sensitive to within‐group anxiety variability than full‐intensity stimuli.

Conclusions

Our results provide novel evidence that although threat‐related attentional biases may correspond with anxiety outcomes in FXS, these associations are complex and vary across developmental and task factors. Future studies are needed to characterise these associations in more robust longitudinal samples, informing whether and how eye‐tracking tasks might be optimised to reliably predict and track anxiety in FXS.
Heart anatomy and topography of the common marmoset (Callithrix jacchus Linnaeus, 1758)
Authors: Falcão Brunna Muniz Rodrigues , de Souza Joyce Galvão , de La Salles Ana Yasha Ferreira , Batista Luan Nascimento , Rocha Ediane Freitas , Diniz João Augusto Rodrigues Alves , Fernandes Annielle Regina Fonseca , dos Santos José Rômulo Soares , de Menezes Danilo José Ayres , Medeiros Gildenor Xavier
Published: February 2020

Introduction

The morphological study of wild animals serves as a base for more advanced studies in clinical medicine, surgery, and pathology. Due to an urgent need and demand for professionals specialized in this area, studies of this nature have become indispensable and so the objective of the present study was to describe the heart morphology of Callithrix jacchus.

Methods

Ten anatomic pieces of common marmoset were used. The hearts were removed and dissected for better visualization and thus to makes a detailed description of the structures of the organ of the C jacchus species.

Results

The C jacchus heart is similar to that of other mammals, with small anatomical modifications such as division of the apex by the interventricular grooves, shallow fossa ovalis, and less salient intervenous tubercle.

Conclusions

This study may serve as taxonomic base for research and also as a basis for clinical and surgical procedures with the C jacchus.