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Πέμπτη 31 Οκτωβρίου 2019

1.
 2019 Oct 29:1-10. doi: 10.1080/19440049.2019.1681594. [Epub ahead of print]

Effects of the cooking modes on commonly used pesticides residue in vegetables and their chronic dietary exposure risk in South China.

Zhao F1,2,3Liu J4,5.

Author information

1
Analysis and Testing Center, Chinese Academy of Tropical Agricultural Sciences, Haikou, China.
2
Hainan Provincial Key Laboratory of Quality and Safety for Tropical Fruits and Vegetables, Haikou, China.
3
Laboratory of Quality and Safety Risk Assessment for Tropical Products, Ministry of Agriculture and Rural Affairs, Haikou, China.
4
Key Laboratory of Agri-food Quality and Safety of Ministry of Agriculture and Rural Affairs, Institute of Quality Standards and Testing Technology for Agro-Products, Chinese Academy of Agricultural Sciences, Beijing, China.
5
Institute of Environment and Plant Protection, Chinese Academy of Tropical Agricultural Sciences, Haikou, China.

Abstract

Effects of cooking modes on the real intake and chronic exposure risk of pesticide residues in vegetables are usually neglected and largely unknown. Four modes of daily meal preparation; chafing dish, soup, salad and stir-frying were studied in this work to clarify their impact on the residual pesticides in foods. A detection method for 14 types of pesticide residues in different cuisines was developed. In this work, chronic exposure risks of four pesticides were analysed by probabilistic assessment based on data from public health and a pesticide residues investigation conducted. The results showed that chafing dish and soup methods greatly lowered the types, contents and exposure risks from residue pesticides. Salad preserved almost all the pesticide residues, and the risks were also relatively high in the stir-frying method. In chafing dish and soup, pesticide residues were dispersed in the media and posed quite low threats to humans. Considering the age, infants and children were at a higher risk of exposure than other populations. Reassuringly, all of the risks were at acceptable levels. This study clarified how the cooking modes affect chronic exposure risks to pesticide residues in the vegetables. The outcomes also show the effects of cooking method on healthy daily diets.

KEYWORDS:

Cuisine methods; exposure risk; health diet; pesticide residue; risk assessment
2.
 2019 Oct 29:1-12. doi: 10.1080/02699052.2019.1682192. [Epub ahead of print]

Patterns of narrative discourse in early recovery following severe Traumatic Brain Injury.

Author information

1
University of Technology Sydney, Graduate School of Health, Sydney, Australia.
2
Discipline of Speech Pathology, Faculty of Health Sciences, The University of Sydney, Sydney, Australia.
3
Department of Speech and Hearing Sciences, The University of New Mexico, Albuquerque, New Mexico, USA.
4
Department of Psychology, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA.

Abstract

Primary Objective: To investigate the nature and patterns of narrative discourse impairment in people with severe Traumatic Brain Injury (TBI) during early recovery.Methods and Procedures: A single image picture description task was administered to 42 participants with severe TBI at 3 and 6-months post-injury. The same task was administered to 37 control participants. Discourse samples were analyzed with measures of productivity, informativeness and story organization. The performance of people with TBI was compared with the control group at both 3 and 6 months, and the performance of the participants with TBI was also compared across the two time points. Individual patterns of performance were also examined.Results: Inferential analyses revealed significant differences between the control group and the group with TBI on informativeness at both time points and  number of complete episodes at 3 months, but no significant differences for productivity measures. There was no significant change for the group with TBI between 3 and 6 months. However, individual improvement over time was observed.Conclusions: People with TBI have discourse difficulties early post TBI that are also present at 6-months post-injury. In order to understand longer-term discourse recovery, it is necessary to examine participant patterns over further time points on this narrative task.

KEYWORDS:

Traumatic brain injury; discourse; early recovery; narrative
3.
 2019 Oct 29. doi: 10.1111/jdi.13166. [Epub ahead of print]

Association between cancer antigen 19-9 and diabetes risk: a prospective and Mendelian randomization study.

Li Z1Wang J1Han X1Wang F1Hu H1Yuan J1Yao P1Wei S2Guo H1Zheng D1Tang Y1Yang H3He M1.

Author information

1
Department of Occupational and Environmental Health, State Key Laboratory of Environmental Health for Incubating, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
2
Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
3
Dongfeng Central Hospital, Dongfeng Motor Corporation and Hubei University of Medicine, Shiyan, Hubei, China.

Abstract

AIMS/INTRODUCTION:

Elevated serum cancer antigen 19-9(CA19-9) levels have been found in diabetes patients in most observational studies; however, whether there is causal association between CA19-9 and diabetes mellitus (DM) is unclear.

MATERIALS AND METHODS:

Our study was conducted based on the Dongfeng-Tongji cohort comprising 27,009 individuals. We first investigated the associations between serum CA19-9 levels and incident DM risk in a prospective cohort study (12,700 individuals). Then, we explored the potential causal relationship between CA19-9 and DM risk in a cross-sectional study (3,349 DM cases and 8,341 controls) using Mendelian randomization analysis. A weighted genetic risk score (GRS) was calculated by adding the CA19-9 increasing alleles in five SNPs (rs17271883, rs3760776 and rs3760775 in FUT6, rs11880333 in CA11, rs265548 in B3GNT3, and rs1047781 in FUT2) which were identified in previous genome-wide association study on serum CA19-9 levels.

RESULTS:

In the prospective study, a total of 1,004 incident DM cases were diagnosed during mean 4.54 years of follow-up period. Elevated serum CA19-9 level was associated with a higher incident diabetes risk after adjustment for confounders, with a HR of 1.20 (95% CI: 1.11, 1.30) per SD (12.17U/ml) CA19-9 increased. Using the genetic score to estimate the unconfounded effect, we did not find causal association of CA19-9 with diabetes risk (OR per weighted CA19-9-increasing allele: 0.99; 95 % CI: 0.94-1.04; P=0.61).

CONCLUSIONS:

The present study does not support a causal association of serum CA19-9 with diabetes risk. CA19-9 might be a potential biomarker of incident DM risk.

KEYWORDS:

Cancer antigen 19-9; Diabetes mellitus; Mendelian randomization
PMID:
 
31661606
 
DOI:
 
10.1111/jdi.13166
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4.
 2019 Oct 29. doi: 10.1111/febs.15103. [Epub ahead of print]

Tracking mitochondria's intra- and inter-organelle signaling.

Author information

1
Gottfried Schatz Research Center, Molecular Biology and Biochemistry, Medical University of Graz, Neue Stiftingtalstraße 6/6, 8010, Graz, Austria.
2
Department of Health Sciences and Technology, ETH Zurich, Schorenstrasse 16, 8603, Schwerzenbach, Switzerland.
3
BioTechMed Graz, Austria.

Abstract

Mitochondria are as highly specialized organelles and masters of the cellular energy metabolism in a constant and dynamic interplay with their cellular environment, providing adenosine trisphosphate, buffering Ca2+ and fundamentally contributing to various signaling pathways. Hence, such broad field of action within eukaryotic cells requires a high level of structural and functional adaptation. Therefore, mitochondria are constantly moving and undergoing fusion and fission processes, changing their shape and their interaction with other organelles. Moreover, mitochondrial activity gets fine-tuned by intra- and inter-organelle H+ , K+ , Na+ and Ca2+ signaling. In this review we provide an up-to-date overview on mitochondrial strategies to adapt and respond to, as well as affect, their cellular environment. We also present cutting-edge technologies used to track and investigate subcellular signaling, essential to the understanding of various physiological and pathophysiological processes.

KEYWORDS:

calcium; intracellular signaling; mitochondria; mitochondria-associated ER membranes; mitochondrial membrane potential; mitochondrial structure; potassium
PMID:
 
31661602
 
DOI:
 
10.1111/febs.15103
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5.
 2019 Oct 29. doi: 10.1039/c9an01512d. [Epub ahead of print]

Rapid detection of synthetic cannabinoids in herbal highs using surface-enhanced Raman scattering produced by gold nanoparticle co-aggregation in a wet system.

Author information

1
Third Department of Forensic Science, National Research Institute of Police Science, 6-3-1, Kashiwanoha, Kashiwa, Chiba 277-0882, Japan. segawa@nrips.go.jp.
2
Department of Micro Engineering, Kyoto University, Kyoto daigaku-Katsura, Nishikyo-ku, Kyoto 615-8540, Japan.
3
Health Research Institute, National Institute of Advanced Industrial Science and Technology, 2217-14, Hayashi-cho, Takamatsu, Kagawa 761-0395, Japan.
4
STRAWB Inc., 1542-1, Nakahara-cho, Takahashi, Okayama 716-0045, Japan.

Abstract

Synthetic cannabinoids (SCs) are a major category of new psychoactive substances that are frequently distributed after addition to plants. To date, various SCs with small differences in their chemical structures have prevailed in the illegal drug market. Thus, the development of a method for rapid detection with high discrimination capability is critically important for the forensic field. Vibrational spectroscopy is a possible analytical technique for this purpose because it can sensitively reflect differences among chemical structures. In this study, we applied surface-enhanced Raman scattering (SERS) with gold nanoparticle co-aggregation in a wet system to plant samples containing SCs. The experimental protocol used was simple and involved only mixing of the sample with several other solutions. It was possible to detect SERS spectra from various stock solutions of SCs by this method. The method was then applied to street samples containing SCs. Some of the plant samples containing SCs did not produce significant SERS signals even though stock solutions of the same SCs did produce SERS spectra. We investigated the reason for this discrepancy and speculated that the solubility in aqueous solutions was a factor determining whether a significant SERS signal could be detected or not. According to this hypothesis, minimal sample pre-treatment methods were applied. This allowed for the detection of SERS spectra from the examined plant samples. The developed approach is a powerful method for screening analysis of SCs in plant fragments.
PMID:
 
31661540
 
DOI:
 
10.1039/c9an01512d
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6.
 2019 Oct 29;14(10):e0223996. doi: 10.1371/journal.pone.0223996. eCollection 2019.

Impact of the detection of ζ-globin chains and hemoglobin Bart's using immunochromatographic strip tests for α0-thalassemia (--SEA) differential diagnosis.

Author information

1
Division of Clinical Immunology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand.
2
Biomedical Technology Research Center, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency at the Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand.
3
Center of Biomolecular Therapy and Diagnostic, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand.
4
Thalassemia Research Center, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand.

Abstract

α0-Thalassemia is an inherited hematological disorder caused by the deletion of α-globin genes. The Southeast Asian deletion (--SEA) is the most common type of α0-thalassemia observed in Southeast Asian countries. Regarding WHO health policy, an effective α0-thalassemia screening strategy is needed to control new severe α-thalassemia cases. In this study, a monoclonal antibody panel was used to develop immunochromatographic (IC) strip tests for detecting the Hb Bart's and ζ-globin chain. Among 195 samples, all α0-thalassemia traits (78 α0-thalassemia (--SEA) and 4 α0-thalassemia (--THAI)) had low MCV or MCH values. The sensitivity, specificity, PPV and NPV of the IC strip tests for ζ-globin and Hb Bart's for screening α0-thalassemia (--SEA) within the low MCV or MCH samples were 100%, 65.2%, 90.7%, 100% and 96.2%, 47.8%, 86.6%, 78.6%, respectively. All 4 α0-thalassemia (--THAI) traits were negative for ζ-globin chains but positive for Hb Bart's using the IC strip tests. These results led to a α0-thalassemia screening being proposed in which blood samples are first evaluated by MCV, MCH and Hb typing. Samples with high MCV and MCH values are excluded for the presence of the α0-thalassemia gene. Samples with low MCV or MCH values are assayed using the developed IC strip tests, where only samples testing positive are further assayed for α0-thalassemia by PCR. Patients with Hb H, EA Bart's or EF Bart's diseases do not need to use this IC strip assay. Thus, in this study, a simple and cost effective α0-thalassemia point of care test was developed.
PMID:
 
31661492
 
DOI:
 
10.1371/journal.pone.0223996
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7.
 2019 Oct 29;14(10):e0215795. doi: 10.1371/journal.pone.0215795. eCollection 2019.

Measuring the impact of an interdisciplinary learning project on nursing, architecture and landscape design students' empathy.

Author information

1
School of Architecture, Department of Design, Architecture and Building, University of Technology, Sydney, Australia.
2
School of Nursing, Faculty of Health, University of Technology, Sydney, Australia.
3
School of Life Science, Faculty of Science, University of Technology, Sydney, Australia.

Abstract

DOMESTIC VIOLENCE AND REFUGE SERVICES IN AUSTRALIA:

In Australia and internationally, domestic violence is a major cause of homelessness for women and children and yet provision for accommodation for this user-group is not well documented or understood. When designing emergency accommodation, the concerns, preferences, and perspectives of individuals who access refuge services must be sought in order to create spaces that are conducive to the needs of this diverse and vulnerable group. An empathic 'lens' can provide meaningful insights that can inform the design of refuge services specifically targeted at addressing these needs. This paper describes an authentic interdisciplinary learning experience for nursing, architecture and landscape students at a university in Sydney, Australia, and presents the results of a study designed to measure the impact of this initiative on participants' empathy towards women and children who access refuge services as a result of homelessness and/or domestic violence. Empathy levels were measured using the Comprehensive State Empathy Scale, a validated measurement tool.

AN AUTHENTIC INTERDISCIPLINARY LEARNING EXPERIENCE:

The learning experience consisted of collaborative meetings with stakeholders from the refuge sector, fieldwork, individual research, exchanging ideas and problem-solving in teams. Students then developed design guides for refuges that demonstrated their emerging understanding of the specific needs and perspectives of the issues faced by women and children who had experienced violence and found themselves homeless. Pre-post Comprehensive State Empathy Scale results indicated that the empathy levels of nursing and landscape students increased and those of architecture students decreased, however, these results were not statistically significant.

BUILDING EMPATHY IN TEACHING AND LEARNING:

The significance of the results from this study include an ability to compare the changes in empathy in students working collaboratively on a project and to ascertain possible reasons for this using a validated measurement tool. As empathy is one of the strongest negative correlates of prejudice, authentic teaching and learning activities, such as the one described in this paper, have the potential to positively impact the lived experience of women and children leaving situations of domestic violence.
PMID:
 
31661491
 
DOI:
 
10.1371/journal.pone.0215795
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8.
 2019 Sep-Oct;53(5):815-829. doi: 10.1134/S0026898419050082.

[Mathematical Modeling of the Intracellular Regulation of Immune Processes].

[Article in Russian]

Author information

1
Moscow Institute of Physics and Technology (National Research University), Dolgoprudny, Moscow Region, 141701 Russia.
2
Marchuk Institute of Numerical Mathematics, Russian Academy of Sciences, Moscow, 119333 Russia.
3
Infection Biology Laboratory, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, 08003 Spain.
4
ICREA, Pg. Iluis Companys 23, Barcelona, 08010 Spain.
5
bocharov@m.inm.ras.ru.

Abstract

The modern era of research in immunology is characterized by an unprecedented level of detail about structural characteristics of the immune system and the regulation of activities of its numerous components, which function together as a whole distributed-parameter system. Mathematical modeling provides an analytical tool to describe, analyze, and predict the dynamics of immune responses by applying a reductionist approach. In modern systems immunology and mathematical immunology as a new interdisciplinary field, a great challenge is to formulate the mathematical models of the human immune system that reflect the level achieved in understanding its structure and describe the processes that sustain its function. To this end, a systematic development of multiscale mathematical models has to be advanced. An appropriate methodology should consider (1) the intracellular processes of immune cell fate regulation, (2) the population dynamics of immune cells in various organs, and (3) systemic immunophysiological processes in the whole host organism. Main studies aimed at modeling the intracellular regulatory networks are reviewed in the context of multiscale mathematical modelling. The processes considered determine the regulation of the immune cell fate, including activation, division, differentiation, apoptosis, and migration. Because of the complexity and high dimensionality of the regulatory networks, identifying the parsimonious descriptions of signaling pathways and regulatory loops is a pressing problem of modern mathematical immunology.

KEYWORDS:

activation; apoptosis; differentiation; immune responses; migration; multiscale modelling; regulatory networks
PMID:
 
31661480
 
DOI:
 
10.1134/S0026898419050082
9.
 2019 Aug;80(4):685-694. doi: 10.2166/wst.2019.312.

A rapid and efficient removal approach for degradation of metformin in pharmaceutical wastewater using electro-Fenton process; optimization by response surface methodology.

Author information

1
Environmental Science and Technology Research Center, Department of Environmental Health Engineering, Shahid Sadoughi University of Medical Sciences, Yazd, Iran and Student Research Committee, Kerman University of Medical Sciences, Kerman, Iran.
2
Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran and Food, Drug and Cosmetics Safety Research Center, Kerman University of Medical Sciences, Kerman, Iran E-mail: saeid.ahmadzadeh@kmu.ac.ir; chem_ahmadzadeh@yahoo.com.

Abstract

Presence of emerging contaminants such as pharmaceutical products in aquatic environments has received high concern due to their undesirable effect on wildlife and human health. Current work deals with developing a treatment model based on the electro- Fenton (EF) process for efficient removal of metformin (MET) from an aqueous medium. The obtained experimental results revealed that over the reaction time of 10 min and solution pH of 3, the maximum removal efficiency of 98.57% is achieved where the value of MET initial concentration, current density, and H2O2 dosage is set at 10 mg.L-1, 6 mA.cm-2, and 250 μL.L-1, respectively, which is in satisfactory agreement with the predicted removal efficiency of 98.6% with the desirability of 0.99. The presence of radical scavengers throughout the mineralization of MET under the EF process revealed that the generation of OH radicals, as the main oxidative species, controlled the degradation mechanism. The obtained kinetics data best fitted to the first order kinetic model with the rate constant of 0.4224 min-1 (R2 = 0.9940). The developed treatment process under response surface methodology (RSM) was employed for modeling the obtained experimental data and successfully applied for efficient removal of the MET contaminant from pharmaceutical wastewater as an adequate and cost-effective approach.
PMID:
 
31661448
 
PMCID:
 
wst_2019_312
 
DOI:
 
10.2166/wst.2019.312
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10.
 2019 Oct;23(60):1-88. doi: 10.3310/hta23600.

Practical help for specifying the target difference in sample size calculations for RCTs: the DELTA2 five-stage study, including a workshop.

Author information

1
Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
2
Medical Statistics Group, School of Health and Related Research, University of Sheffield, Sheffield, UK.
3
Statistical Methodology and Consulting, Novartis Pharma AG, Basel, Switzerland.
4
York Trials Unit, Department of Health Sciences, University of York, York, UK.
5
Johnson & Johnson, Titusville, NJ, USA.
6
Imperial Clinical Trials Unit, Imperial College London, London, UK.
7
Department of Biostatistics and Health Informatics, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
8
Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
9
Cambridge Centre for Health Services Research, Cambridge Clinical Trials Unit University of Cambridge, Cambridge, UK.
10
Health Economics Group, Norwich Medical School, University of East Anglia, Norwich, UK.
11
Centre for Healthcare Randomised Trials, University of Aberdeen, Aberdeen, UK.
12
Warwick Medical School, Statistics and Epidemiology, University of Warwick, Coventry, UK.
13
Department of Health Sciences, University of York, York, UK.
14
MRC Clinical Trials Unit, Institute of Clinical Trials and Methodology, University College London, London, UK.
15
Health Services Research Unit, University of Aberdeen, Aberdeen, UK.
16
Wessex Institute, University of Southampton, Southampton, UK.
17
School of Population Health and Environmental Sciences, King's College London, London, UK.
18
Health Economics Group, Institute of Health & Society, Newcastle University, Newcastle upon Tyne, UK.

Abstract

BACKGROUND:

The randomised controlled trial is widely considered to be the gold standard study for comparing the effectiveness of health interventions. Central to its design is a calculation of the number of participants needed (the sample size) for the trial. The sample size is typically calculated by specifying the magnitude of the difference in the primary outcome between the intervention effects for the population of interest. This difference is called the 'target difference' and should be appropriate for the principal estimand of interest and determined by the primary aim of the study. The target difference between treatments should be considered realistic and/or important by one or more key stakeholder groups.

OBJECTIVE:

The objective of the report is to provide practical help on the choice of target difference used in the sample size calculation for a randomised controlled trial for researchers and funder representatives.

METHODS:

The Difference ELicitation in TriAls2 (DELTA2) recommendations and advice were developed through a five-stage process, which included two literature reviews of existing funder guidance and recent methodological literature; a Delphi process to engage with a wider group of stakeholders; a 2-day workshop; and finalising the core document.

RESULTS:

Advice is provided for definitive trials (Phase III/IV studies). Methods for choosing the target difference are reviewed. To aid those new to the topic, and to encourage better practice, 10 recommendations are made regarding choosing the target difference and undertaking a sample size calculation. Recommended reporting items for trial proposal, protocols and results papers under the conventional approach are also provided. Case studies reflecting different trial designs and covering different conditions are provided. Alternative trial designs and methods for choosing the sample size are also briefly considered.

CONCLUSIONS:

Choosing an appropriate sample size is crucial if a study is to inform clinical practice. The number of patients recruited into the trial needs to be sufficient to answer the objectives; however, the number should not be higher than necessary to avoid unnecessary burden on patients and wasting precious resources. The choice of the target difference is a key part of this process under the conventional approach to sample size calculations. This document provides advice and recommendations to improve practice and reporting regarding this aspect of trial design. Future work could extend the work to address other less common approaches to the sample size calculations, particularly in terms of appropriate reporting items.

FUNDING:

Funded by the Medical Research Council (MRC) UK and the National Institute for Health Research as part of the MRC-National Institute for Health Research Methodology Research programme.

PLAIN-LANGUAGE-SUMMARY:

This Difference ELicitation in TriAls2 (DELTA2) advice and recommendations document aims to help researchers choose the ‘target difference’ in a type of research study called a randomised controlled trial. The number of people needed to be involved in a study – the sample size – is usually based on a calculation aimed to ensure that the difference in benefit between treatments is likely to be detected. The calculation also accounts for the risk of a false-positive finding. No more patients than necessary should be involved. Choosing a ‘target difference’ is an important step in calculating the sample size. The target difference is defined as the amount of difference in the participants’ response to the treatments that we wish to detect. It is probably the most important piece of information used in the sample size calculation. How we decide what the target difference should be depends on various factors. One key decision to make is how we should measure the benefits that treatments offer. For example, if we are evaluating a treatment for high blood pressure, the obvious thing to focus on would be blood pressure. We could then proceed to consider what an important difference in blood pressure between treatments would be, based on experts’ views or evidence from previous research studies. This document seeks to provide assistance to researchers on how to choose the target difference when designing a trial. It also provides advice to help them clearly present what was done and why, when writing up the study proposal or reporting the study’s findings. The document is also intended to be read by those who decide whether or not a proposed study should be funded. Clarifying a study’s aim and getting a sensible sample size is important. It can affect not only those involved in the study, but also future patients who will receive treatment.

KEYWORDS:

MINIMAL CLINICALLY IMPORTANT DIFFERENCE; PEER REVIEW; RANDOMISED CONTROLLED TRIALS; RESEARCH DESIGN; SAMPLE SIZE
PMID:
 
31661431
 
DOI:
 
10.3310/hta23600
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11.
 2019 Nov;22(11):1298-1299. doi: 10.1089/jpm.2019.0483.

Death Took a Vacation … and It's Almost Over.

Author information

1
IMPACCT (Improving Palliative, Aged, and Chronic Care Through Clinical Research and Translation), Faculty of Health, University of Technology Sydney, Ultimo, New South Wales, Australia.
2
Wolfson Palliative Care Research Centre, University of Hull, Hull, United Kingdom.
3
Institute for Clinical and Applied Health Research, Hull York Medical School, University of Hull, Hull, United Kingdom.
PMID:
 
31661391
 
DOI:
 
10.1089/jpm.2019.0483
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12.
 2019 Oct 29:1-10. doi: 10.1080/09168451.2019.1676696. [Epub ahead of print]

Antibiotics can cause weight loss by impairing gut microbiota in mice and the potent benefits of lactobacilli.

Author information

1
Department of Nutrition, Food Hygiene and Toxicology, West China School of Public Health and West China Fourth Hospital, and Healthy Food Evaluation Research Center, Sichuan University, Chengdu, Sichuan, PR China.
2
Sichuan Acadmey of Food and Fermentation Industries, Chengdu, Sichuan, PR China.
3
Sichuan Dongpo Chinese Paocai Industrial Technology Research Institute, Chengdu, Sichuan, PR China.

Abstract

This study assessed whether antibiotics could alter gut microbiota to affect host growth and the possibility of alleviation by lactobacilli. We divided four-week-old BABL/c mice into control (Ctrl), antibiotic exposure (Abx), Lactobacillus plantarum PC-170 (PC), and Lactobacillus rhamnosus GG (LGG) group and the Abx, LGG, and PC group received an one-week antibiotic/antibiotic + probiotic treatment. The fecal microbiota and the expression of splenic cytokines were determined. Following the ceftriaxone treatment, the body weight gain of Abx was delayed compared with others. The ceftriaxone treatment significantly decreased the alpha-diversity of the fecal microbiota and altered the fecal microbiota but LGG and PC can partly alleviate the effect. At the end of the study, the microbial community of LGG and PC group were more similar to Ctrl compared with Abx group. The results indicated that ceftriaxone could significantly alter intestinal microbiota. Lactobacilli might alleviate the side effects of antibiotics by stabilizing the intestinal microbiota.

KEYWORDS:

Akkermansia; Lactobacillus plantarum PC-170; Lactobacillus rhamnosus GG; antibiotic; gut microbiota
13.
 2019 Oct 29:1-13. doi: 10.1080/10408398.2019.1680950. [Epub ahead of print]

Effects of resistant starch on glycemic control, serum lipoproteins and systemic inflammation in patients with metabolic syndrome and related disorders: A systematic review and meta-analysis of randomized controlled clinical trials.

Author information

1
Department of Biochemistry and Nutrition, Research Center for Evidence-Based Health Management, Maraghe University of Medical Science, Maraghe, Iran.
2
Students' Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran.
3
Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.
4
Department of Internal Medicine, University Hospital Centre Zagreb, School of Medicine, University of Zagreb, Zagreb, Croatia.
5
Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran.
6
Indigenous and Global Health Research, Department of Medicine, University of Alberta, Edmonton, Canada.
7
Department of Regenerative Biomedicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
8
Metabolic Diseases Research Center, Research Institute for Prevention of Non-Communicable Diseases, Qazvin University of Medical Sciences, Qazvin, Iran.

Abstract

The aim of this systematic review and meta-analysis was to evaluate the effects of resistant starch (RS) on glycemic status, serum lipoproteins and inflammatory markers in patients with metabolic syndrome (MetS) and related disorders. Two independent authors systematically searched online database including EMBASE, Scopus, PubMed, Cochrane Library, and Web of Science from inception until 30 April 2019. Cochrane Collaboration risk of bias tool was applied to assess the methodological quality of included trials. The heterogeneity among the included studies was assessed using Cochrane's Q test and I-square (I2) statistic. Data were pooled using a random-effects model and weighted mean difference (WMD) was considered as the overall effect size. Nineteen trials were included in this meta-analysis. Administration of RS resulted in significant reduction in fasting plasma glucose (FPG) (14 studies) (WMD: -4.28; 95% CI: -7.01, -1.55), insulin (12 studies) (WMD: -1.95; 95% CI: -3.22, -0.68), and HbA1C (8 studies) (WMD: -0.60; 95% CI: -0.95, -0.24). When pooling data from 13 studies, a significant reduction in total cholesterol levels (WMD: -8.19; 95% CI: -15.38, -1.00) and LDL-cholesterol (WMD: -8.57; 95% CI: -13.48, -3.66) were found as well. Finally, RS administration was associated with a significant decrease in tumor necrosis factor alpha (TNF-α) (WMD: -2.02; 95% CI: -3.14, -0.90). This meta-analysis showed beneficial effects of RS on improving FPG, insulin, HbA1c, total cholesterol, LDL-cholesterol and TNF-α levels in patients with MetS and related disorders, but it did not affect HOMA-IR, triglycerides, HDL-cholesterol, CRP and IL-6 levels.

KEYWORDS:

HDL-cholesterol; LDL-cholesterol; Resistant starch; insulin resistance; meta-analysis; metabolic syndrome
14.
 2019 Oct 25. doi: 10.3892/or.2019.7391. [Epub ahead of print]

Transcriptome analysis of dog oral melanoma and its oncogenic analogy with human melanoma.

Author information

1
Veterinary Teaching Hospital, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima 890‑0065, Japan.
2
Joint Graduate School of Veterinary Medicine, Kagoshima University, Kagoshima 890‑0065, Japan.
3
Department of Veterinary Surgery, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113‑8657, Japan.
4
Hygiene and Health Promotion Medicine, Kagoshima University Graduate School of Medicine and Dental Science, Kagoshima University, Kagoshima 890‑0065, Japan.
5
Department of Veterinary Histopathology, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima 890‑0065, Japan.
6
Animal Medical Center, Tokyo University of Agriculture and Technology, Tokyo 183‑8538, Japan.

Abstract

Dogs have been considered as an excellent immunocompetent model for human melanoma due to the same tumor location and the common clinical and pathological features with human melanoma. However, the differences in the melanoma transcriptome between the two species have not been yet fully determined. Considering the role of oncogenes in melanoma development, in this study, we first characterized the transcriptome in canine oral melanoma and then compared the transcriptome with that of human melanoma. The global transcriptome from 8 canine oral melanoma samples and 3 healthy oral tissues were compared by RNA‑Seq followed by RT‑qPCR validation. The results revealed 2,555 annotated differentially expressed genes, as well as 364 novel differentially expressed genes. Dog chromosomes 1 and 9 were enriched with downregulated and upregulated genes, respectively. Along with 10 significant transcription site binding motifs; the NF‑κB and ATF1 binding motifs were the most significant and 4 significant unknown motifs were indentified among the upregulated differentially expressed genes. Moreover, it was found that canine oral melanoma shared >80% significant oncogenes (upregulated genes) with human melanoma, and JAK‑STAT was the most common significant pathway between the species. The results identified a 429 gene signature in melanoma, which was up‑regulated in both species; these genes may be good candidates for therapeutic development. Furthermore, this study demonstrates that as regards oncogene expression, human melanoma contains an oncogene group that bears similarities with dog oral melanoma, which supports the use of dogs as a model for the development of novel therapeutics and experimental trials before human application.
PMID:
 
31661138
 
DOI:
 
10.3892/or.2019.7391
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15.
 2019 Oct 24. doi: 10.3892/ijmm.2019.4383. [Epub ahead of print]

Roles of p38α and p38β mitogen‑activated protein kinase isoforms in human malignant melanoma A375 cells.

Author information

1
Department of Dermatology, Taipei City Hospital, Renai Branch, Taipei 106, Taiwan, R.O.C.
2
Department of Medical Education and Research and Department of Obstetrics and Gynecology, China Medical University Beigang Hospital, Yunlin 65152, Taiwan, R.O.C.
3
Department of Biological Science and Technology, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung 404, Taiwan, R.O.C.
4
Department of Biology, Georgia State University, Atlanta, GA 30303, USA.
5
Division of Breast Surgery, Department of Surgery, China Medical University Hospital, Taichung 404, Taiwan, R.O.C.
6
Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404, Taiwan, R.O.C.

Abstract

Skin cancer is one of the most common cancers worldwide. Melanoma accounts for ~5% of skin cancers but causes the large majority of skin cancer‑related deaths. Recent discoveries have shown that the mitogen‑activated protein kinase (MAPK) signaling pathway is critical for melanoma development and progression. Many oncogenic pathways that cause melanoma tumorigenesis have been identified, most of which are due to RAF/MEK/ERK (MAPK) pathway activation. However, the precise role of p38 remains unclear. Using specific short hairpin (sh) RNA to silence p38α and p38β, the present findings demonstrated that p38α was a crucial factor in regulating cell migration in the A375 melanoma cell line. Silencing p38α downregulated the expression of epithelial‑mesenchymal transition markers, such as matrix metallopeptidase (MMP) 2, MMP9, twist family bHLH transcription factor 1, snail family transcriptional repressor 1 and vimentin, while mesenchymal‑epithelial transition markers, such as E‑cadherin, were upregulated. Of note, the results also demonstrated that p38α silencing impaired vascular endothelial growth factor expression, which regulates tumor angiogenesis. Furthermore, p38α knockdown inhibited cell proliferation in melanoma cells. In addition, silencing p38α induced senescence‑like features, but not cell cycle arrest. Expression of the senescence markers p16, p21, p53 and β‑galactosidase was upregulated, and an increase in the number of senescence‑associated β‑galactosidase‑positive cells was observed in a p38α knockdown stable clone. However, no significant difference was found between control and p38β stable knockdown cells. Taken together, the present results suggested that p38α knockdown impaired migration and proliferation, and increased senescence, in A375 melanoma cells. However, p38β may not be involved in melanoma tumorigenesis. Therefore, targeting p38α may be a valuable approach towards inhibiting tumor growth and metastasis in patients with melanoma.
PMID:
 
31661126
 
DOI:
 
10.3892/ijmm.2019.4383
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16.
 2019 Oct 28;7(4):e14603. doi: 10.2196/14603.

Challenges With Continuous Pulse Oximetry Monitoring and Wireless Clinician Notification Systems After Surgery: Reactive Analysis of a Randomized Controlled Trial.

Author information

1
Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada.
2
Department of Anesthesia, McMaster University, Hamilton, ON, Canada.
3
Western University, London, ON, Canada.
4
St. Joseph's Healthcare, Hamilton, ON, Canada.
5
Hamilton Health Sciences, Hamilton, ON, Canada.
6
School of Nursing, McMaster University, Hamilton, ON, Canada.

Abstract

BACKGROUND:

Research has shown that introducing electronic Health (eHealth) patient monitoring interventions can improve healthcare efficiency and clinical outcomes. The VIGILANCE (VItal siGns monItoring with continuous puLse oximetry And wireless cliNiCian notification aftEr surgery) study was a randomized controlled trial (n=2049) designed to assess the impact of continuous vital sign monitoring with alerts sent to nursing staff when respiratory resuscitations with naloxone, code blues, and intensive care unit transfers occurred in a cohort of postsurgical patients in a ward setting. This report identifies and evaluates key issues and challenges associated with introducing wireless monitoring systems into complex hospital infrastructure during the VIGILANCE eHealth intervention implementation. Potential solutions and suggestions for future implementation research are presented.

OBJECTIVE:

The goals of this study were to: (1) identify issues related to the deployment of the eHealth intervention system of the VIGILANCE study; and (2) evaluate the influence of these issues on intervention adoption.

METHODS:

During the VIGILANCE study, issues affecting the implementation of the eHealth intervention were documented on case report forms, alarm event forms, and a nursing user feedback questionnaire. These data were collated by the research and nursing personnel and submitted to the research coordinator. In this evaluation report, the clinical adoption framework was used as a guide to organize the identified issues and evaluate their impact.

RESULTS:

Using the clinical adoption framework, we identified issues within the framework dimensions of people, organization, and implementation at the meso level, as well as standards and funding issues at the macro level. Key issues included: nursing workflow changes with blank alarm forms (24/1030, 2.33%) and missing alarm forms (236/1030, 22.91%), patient withdrawal (110/1030, 10.68%), wireless network connectivity, false alarms (318/1030, 30.87%), monitor malfunction (36/1030, 3.49%), probe issues (16/1030, 1.55%), and wireless network standards. At the micro level, these issues affected the quality of the service in terms of support provided, the quality of the information yielded by the monitors, and the functionality, reliability, and performance of the monitoring system. As a result, these issues impacted access through the decreased ability of nurses to make complete use of the monitors, impacted care quality of the trial intervention through decreased effectiveness, and impacted productivity through interference in the coordination of care, thus decreasing clinical adoption of the monitoring system.

CONCLUSIONS:

Patient monitoring with eHealth technology in surgical wards has the potential to improve patient outcomes. However, proper planning that includes engagement of front-line nurses, installation of appropriate wireless network infrastructure, and use of comfortable cableless devices is required to maximize the potential of eHealth monitoring.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT02907255; https://clinicaltrials.gov/ct2/show/NCT02907255.

KEYWORDS:

clinical adoption framework; continuous pulse oximetry; evaluation of issues; false alarm; issues; postoperative monitoring; remote monitoring; wireless notification
PMID:
 
31661079
 
DOI:
 
10.2196/14603
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17.
 2019 Oct;23(59):1-208. doi: 10.3310/hta23590.

An intervention to improve outcomes of falls in dementia: the DIFRID mixed-methods feasibility study.

Author information

1
University of Exeter Medical School, University of Exeter, Exeter, UK.
2
Institute of Health and Society, Newcastle University, Newcastle upon Tyne, UK.
3
Department of Occupational Therapy, Tees, Esk and Wear Valleys NHS Foundation Trust, Stockton-on-Tees, UK.
4
Department of Physiotherapy, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
5
Norwich Medical School, University of East Anglia, Norwich, UK.
6
Department of Old Age Psychiatry, Northumberland Tyne and Wear NHS Foundation Trust, Newcastle upon Tyne, UK.
7
Department of Emergency Medicine, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
8
Falls and Syncope Service, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
9
Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK.
10
VOICE, Newcastle University, Newcastle upon Tyne, UK.

Abstract

BACKGROUND:

Fall-related injuries are a significant cause of morbidity and mortality in people with dementia. There is presently little evidence to guide the management of such injuries, and yet there are potentially substantial benefits to be gained if the outcomes of these injuries could be improved. This study aimed to design an appropriate new health-care intervention for people with dementia following a fall and to assess the feasibility of its delivery in the UK NHS.

OBJECTIVES:

To determine whether or not it is possible to design an intervention to improve outcomes of falls in dementia, to investigate the feasibility and acceptability of the DIFRID (Developing an Intervention for Fall related Injuries in Dementia) intervention and to investigate the feasibility of a future randomised controlled trial and the data collection tools needed to evaluate both the effectiveness and the cost-effectiveness of the DIFRID intervention.

DESIGN:

This was a mixed-methods feasibility study. A systematic review (using Cochrane methodology) and realist review [using Realist And Meta-narrative Evidence Syntheses: Evolving Standards (RAMESES) methodology] explored the existing evidence base and developed programme theories. Searches were carried out in November 2015 (updated in January 2018) for effectiveness studies and in August 2016 for economic studies. A prospective observational study identified service use via participant diary completion. Qualitative methods (semistructured interviews, focus groups and observation) were used to explore current practice, stakeholder perspectives of the health and social care needs of people with dementia following a fall, ideas for intervention and barriers to and facilitators of change. Each of the resulting data sets informed intervention development via Delphi consensus methods. Finally, a single-arm feasibility study with embedded process evaluation was conducted.

SETTING:

This study was set in the community.

PARTICIPANTS:

The participants were (1) people with dementia presenting with falls necessitating health-care attention in each setting (primary care, the community and secondary care) at three sites and their carers, (2) professionals delivering the intervention, who were responsible for training and supervision and who were members of the intervention team, (3) professionals responsible for approaching and recruiting participants and (4) carers of participants with dementia.

INTERVENTIONS:

This was a complex multidisciplinary therapy intervention. Physiotherapists, occupational therapists and support workers delivered up to 22 sessions of tailored activities in the home or local area of the person with dementia over a period of 12 weeks.

MAIN OUTCOME MEASURES:

(1) Assessment of feasibility of study procedures; (2) assessment of the acceptability, feasibility and fidelity of intervention components; and (3) assessment of the suitability and acceptability of outcome measures for people with dementia and their carers (number of falls, quality of life, fear of falling, activities of daily living, goal-setting, health-care utilisation and carer burden).

RESULTS:

A multidisciplinary intervention delivered in the homes of people with dementia was designed based on qualitative work, realist review and recommendations of the consensus panel. The intervention was delivered to 11 people with dementia. The study suggested that the intervention is both feasible and acceptable to stakeholders. A number of modifications were recommended to address some of the issues arising during feasibility testing. The measurement of outcome measures was successful.

CONCLUSIONS:

The study has highlighted the feasibility of delivering a creative, tailored, individual approach to intervention for people with dementia following a fall. Although the intervention required greater investment of time than usual practice, many staff valued the opportunity to work more closely with people with dementia and their carers. We conclude that further research is now needed to refine this intervention in the context of a pilot randomised controlled trial.

TRIAL REGISTRATION:

Current Controlled Trials ISRCTN41760734 and PROSPERO CRD42016029565.

FUNDING:

This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 59. See the NIHR Journals Library website for further project information.

PLAIN-LANGUAGE-SUMMARY:

People with dementia fall over more often than people who do not have dementia. When they fall over, they are more likely to hurt themselves. They do not get better as easily as people without dementia. After hurting themselves, people with dementia may need a lot more help in looking after themselves. They, and their carer, may not have such a good quality of life after the fall. In this study, we developed and tested a package of care to help people with dementia recover from a fall. In the first part of the study, we looked for papers about clinical trials that have tried to make things better for people with dementia who have had a fall. We found that there were very few previous clinical trials, but we found ideas for ways in which this could be improved. In the second part of the study, we found out what happens to people with dementia who ask for help after an injury due to a fall. We found that very few services were used by people with dementia who fall. We interviewed them and their carers to find out what help they thought they needed after the fall and what they thought we could do better. We also spoke to the staff in existing services to find out how they thought services for people with dementia could be improved. In the third part of the study, we asked a group of experts, people with dementia and their carers to look at the findings of the first two parts of the study. They helped us to design a care package for people with dementia after a fall. In the fourth part of the study, we practised giving the new care package to 11 people with dementia in their own homes. This was very successful and we now recommend that the package is tested further in randomised controlled clinical trials.

KEYWORDS:

ACCIDENTAL FALLS; DEMENTIA; HEALTH SERVICES NEEDS AND DEMAND; INTERVENTIONS; PILOTS; PROSPECTIVE STUDIES
PMID:
 
31661058
 
DOI:
 
10.3310/hta23590
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18.
 2019 Oct 28;8(1):244. doi: 10.1186/s13643-019-1176-4.

Psychological interventions for alcohol use disorders in people living with HIV/AIDS: a systematic review.

Author information

1
Department of Psychiatry, College of Health Sciences, University of Zimbabwe, Harare, Zimbabwe. mmadhombiro@gmail.com.
2
Centre for Evidence-based Health Care, Division of Epidemiology and Biostatistics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
3
Department of Community Medicine, College of Health Sciences, University of Zimbabwe, Harare, Zimbabwe.
4
Department of Psychiatry, College of Health Sciences, University of Zimbabwe, Harare, Zimbabwe.
5
King's College London, Centre for Global Mental Health, David Goldberg Centre H1.12, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, London, SE5 8AF, UK.
6
Department of Psychiatry, Faculty of Medicine and Health Sciences, University of Stellenbosch, Francie van Zijl Avenue, 7505, Cape Town, South Africa.

Abstract

BACKGROUND:

Alcohol use disorders (AUDs) in people living with HIV/AIDS (PLWH) are a significant impediment to achieving virological control. HIV non-suppression in PLWH with AUDs is mainly attributable to sub-optimal antiretroviral therapy adherence. Sub-optimal adherence makes control of the epidemic elusive, considering that effective antiretroviral treatment and viral suppression are the two key pillars in reducing new infections. Psychological interventions have been proposed as effective treatments for the management of AUDs in PLWH. Evidence for their effectiveness has been inconsistent, with two reviews (2010 and 2013) concluding a lack of effectiveness. However, a 2017 review that examined multiple HIV prevention and treatment outcomes suggested that behavioural interventions were effective in reducing alcohol use. Since then, several studies have been published necessitating a re-examination of this evidence. This review provides an updated synthesis of the effectiveness of psychological interventions for AUDs in PLWH.

METHODS:

A search was conducted in the following databases: PubMed, Cochrane Central Register of Trials (CENTRAL), MEDLINE (Ovid), EMBASE, PsychInfo (Ovid) and Clinical trials.gov (clinicaltrials.gov) for eligible studies until August 2018 for psychotherapy and psychosocial interventions for PLWH with AUDs. Two reviewers independently screened titles, abstracts and full texts to select studies that met the inclusion criteria. Two reviewers independently performed data extraction with any differences resolved through discussion. Risk of bias was assessed by two independent reviewers using the Cochrane risk of bias tool, and the concordance between the first and second reviewers was 0.63 and between the first and third reviewers 0.71. Inclusion criteria were randomised controlled trials using psychological interventions in people aged 16 and above, with comparisons being usual care, enhanced usual care, other active treatments or waitlist controls.

RESULTS:

A total of 21 studies (6954 participants) were included in this review. Studies had diverse populations including men alone, men and women and men who had sex with men (MSM). Use of motivational interviewing alone or blended with cognitive behavioural therapy (CBT) and technology/computer-assisted platforms were common as individual-level interventions, while a few studies investigated group motivational interviewing or CBT. Alcohol use outcomes were all self-report and included assessment of the quantity and the frequency of alcohol use. Measured secondary outcomes included viral load, CD4 count or other self-reported outcomes. There was a lack of evidence for significant intervention effects in the included studies. Isolated effects of motivational interviewing, cognitive behavioural therapy and group therapy were noted. However for some of the studies that found significant effects, the effect sizes were small and not sustained over time. Owing to the variation in outcome measures employed across studies, no meta-analysis could be carried out.

CONCLUSION:

This systematic review did not reveal large or sustained intervention effects of psychological interventions for either primary alcohol use or secondary HIV-related outcomes. Due to the methodological heterogeneity, we were unable to undertake a meta-analysis. Effectiveness trials of psychological interventions for AUDs in PLWH that include disaggregation of data by level of alcohol consumption, gender and age are needed. There is a need to standardise alcohol use outcome measures across studies and include objective biomarkers that provide a more accurate measure of alcohol consumption and are relatively free from social desirability bias.

SYSTEMATIC REVIEW REGISTRATION:

PROSPERO CRD  42017063856 .

KEYWORDS:

Alcohol; Brief; Cognitive; HIV; Interventions; Motivational; Psychological; Screening; Systematic review
PMID:
 
31661030
 
DOI:
 
10.1186/s13643-019-1176-4
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19.
 2019 Oct 28;8(1):243. doi: 10.1186/s13643-019-1162-x.

Measuring the impact of screening automation on meta-analyses of diagnostic test accuracy.

Author information

1
LIMSI, CNRS, Université Paris Saclay, Rue du Belvedère, Orsay, 91405, France. christopher.norman@limsi.fr.
2
Amsterdam Public Health, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, Amsterdam, 1105 AZ, the Netherlands. christopher.norman@limsi.fr.
3
Amsterdam Public Health, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, Amsterdam, 1105 AZ, the Netherlands.
4
Center for Clinical Epidemiology, Assistance Publique-Hôpitaux de Paris, Hôtel Dieu Hospital; Team METHODS, CRESS, INSERM U1153; University Paris Descartes, 1 place du Parvis Notre-Dame, Paris, 75004, France.
5
LIMSI, CNRS, Université Paris Saclay, Rue du Belvedère, Orsay, 91405, France.

Abstract

BACKGROUND:

The large and increasing number of new studies published each year is making literature identification in systematic reviews ever more time-consuming and costly. Technological assistance has been suggested as an alternative to the conventional, manual study identification to mitigate the cost, but previous literature has mainly evaluated methods in terms of recall (search sensitivity) and workload reduction. There is a need to also evaluate whether screening prioritization methods leads to the same results and conclusions as exhaustive manual screening. In this study, we examined the impact of one screening prioritization method based on active learning on sensitivity and specificity estimates in systematic reviews of diagnostic test accuracy.

METHODS:

We simulated the screening process in 48 Cochrane reviews of diagnostic test accuracy and re-run 400 meta-analyses based on a least 3 studies. We compared screening prioritization (with technological assistance) and screening in randomized order (standard practice without technology assistance). We examined if the screening could have been stopped before identifying all relevant studies while still producing reliable summary estimates. For all meta-analyses, we also examined the relationship between the number of relevant studies and the reliability of the final estimates.

RESULTS:

The main meta-analysis in each systematic review could have been performed after screening an average of 30% of the candidate articles (range 0.07 to 100%). No systematic review would have required screening more than 2308 studies, whereas manual screening would have required screening up to 43,363 studies. Despite an average 70% recall, the estimation error would have been 1.3% on average, compared to an average 2% estimation error expected when replicating summary estimate calculations.

CONCLUSION:

Screening prioritization coupled with stopping criteria in diagnostic test accuracy reviews can reliably detect when the screening process has identified a sufficient number of studies to perform the main meta-analysis with an accuracy within pre-specified tolerance limits. However, many of the systematic reviews did not identify a sufficient number of studies that the meta-analyses were accurate within a 2% limit even with exhaustive manual screening, i.e., using current practice.

KEYWORDS:

*Machine learning; *Systematic review as topic; Evidence based medicine; Natural language processing/*methods
PMID:
 
31661028
 
DOI:
 
10.1186/s13643-019-1162-x
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20.
 2019 Oct 28;16(1):39. doi: 10.1186/s12989-019-0320-6.

Role of chemical composition and redox modification of poorly soluble nanomaterials on their ability to enhance allergic airway sensitisation in mice.

Author information

1
National Institute for Public Health and the Environment (RIVM), P.O.Box 1, 3720 BA, Bilthoven, The Netherlands. susan.dekkers@rivm.nl.
2
Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, MI, USA.
3
National Institute for Public Health and the Environment (RIVM), P.O.Box 1, 3720 BA, Bilthoven, The Netherlands.
4
Promethean Particles Ltd, Nottingham, UK.
5
Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.
6
School of Geography, Earth and Environmental Sciences, University of Birmingham, Birmingham, UK.
7
Institute for Risk Assessment Sciences, Utrecht University, Utrecht, the Netherlands.

Abstract

BACKGROUND:

Engineered nanoparticles (NPs) have been shown to enhance allergic airways disease in mice. However, the influence of the different physicochemical properties of these particles on their adjuvant properties is largely unknown. Here we investigate the effects of chemical composition and redox activity of poorly soluble NPs on their adjuvant potency in a mouse model of airway hypersensitivity.

RESULTS:

NPs of roughly similar sizes with different chemical composition and redox activity, including CeO2, Zr-doped CeO2, Co3O4, Fe-doped Co3O4(using Fe2O3 or Fe3O4) and TiO2 NPs, all showed adjuvant activity. OVA induced immune responses following intranasal exposure of BALB/c mice to 0.02% OVA in combination with 200 μg NPs during sensitization (on day 1, 3, 6 and 8) and 0.5% OVA only during challenge (day 22, 23 and 24) were more pronounced compared to the same OVA treatment regime without NPs. Changes in OVA-specific IgE and IgG1 plasma levels, differential cell count and cytokines in bronchoalveolar lavage fluid (BALF), and histopathological detection of mucosa cell metaplasia and eosinophil density in the conducting airways were observed. Adjuvant activity of the CeO2 NPs was primarily mediated via the Th2 response, while that of the Co3O4 NPs was characterised by no or less marked increases in IgE plasma levels, BALF IL-4 and IL-5 concentrations and percentages of eosinophils in BALF and more pronounced increases in BALF IL-6 concentrations and percentages of lymphocytes in BALF. Co-exposure to Co3O4 NPs with OVA and subsequent OVA challenge also induced perivascular and peribronchiolar lymphoid cell accumulation and formation of ectopic lymphoid tissue in lungs. Responses to OVA combined with various NPs were not affected by the amount of doping or redox activity of the NPs.

CONCLUSIONS:

The findings indicate that chemical composition of NPs influences both the relative potency of NPs to exacerbate allergic airway sensitization and the type of immune response. However, no relation between the acellular redox activity and the observed adjuvant activity of the different NPs was found. Further research is needed to pinpoint the precise physiological properties of NPs and biological mechanisms determining adjuvant activity in order to facilitate a safe-by-design approach to NP development.

KEYWORDS:

Adjuvant; Allergy, Poorly soluble; Cobalt oxide, Cerium dioxide; Nanomaterials; Redox activity
PMID:
 
31660999
 
DOI:
 
10.1186/s12989-019-0320-6
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