bluuebunny/crossref_metadata_2025 huggingface dataset:
Age-related changes of cholestanol and lathosterol plasma concentrations: an explorative study
Authors: Gelzo Monica , Di Taranto Maria Donata , Sica Concetta , Boscia Antonio , Papagni Francesco , Fortunato Giuliana , Corso Gaetano , Dello Russo Antonio
Published: December 2019

Background

Cerebrotendinous xanthomatosis (CTX) and Lathosterolosis represent two treatable inherited disorders of cholesterol metabolism that are characterized by the accumulation of cholestanol and lathosterol, respectively. The age of the patients suspected of having these disorders is highly variable due to the very different phenotypes. The early diagnosis of these disorders is important because specific therapeutic treatment could prevent the disease progression. The biochemical diagnosis of these defects is generally performed analyzing the sterol profile.

Since age-related levels of these sterols are lacking, this study aims to determine a preliminary comparison of plasma levels of cholestanol and lathosterol among Italian unaffected newborns, children and healthy adults.

Methods

The sterols were extracted from 130 plasma samples (24 newborns, 33 children and 73 adults) by a liquid-liquid separation method and quantified by gas chromatography coupled with a flame ionization detector.

Results

Cholesterol, cholestanol and lathosterol levels together with the cholestanol/cholesterol and lathosterol/cholesterol ratios are statistically different among the three groups. Cholesterol levels progressively increased from newborns to children and to adults, whereas cholestanol/cholesterol and cholestanol/lathosterol ratios progressively decreased from newborns to children and to adults. Lathosterol levels were higher in adults than in both newborns and children. In the total population a positive correlation was observed between cholesterol levels and both cholestanol (correlation coefficient = 0.290,p = 0.001) and lathosterol levels (correlation coefficient = 0.353,p <  0.0001).

Conclusions

Although this study can only be considered an explorative experience due to the low number of analyzed samples, we revealed several differences of plasma cholestanol and lathosterol levels and their ratios to cholesterol levels among newborns, children and adults. These evidences indicate the need of age-related reference values of cholestanol and lathosterol concentrations, including also newborns and children.
The important role of connexin 43 in subarachnoid hemorrhage-induced cerebral vasospasm
Authors: Yang Le , Yan Jian , Zhang Jin-An , Zhou Xin-Hui , Fang Chao , Zeng Er-Ming , Tang Bin , Duan Jian , Lu Guo-Hui , Hong Tao
Published: December 2019

Background

Gap junctions are involved in the development of cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH). However, the specific roles and regulatory functions of related connexin isoforms remain unknown. The aim of this study was to investigate the importance of connexin 43 (Cx43) in CVS and determine whether Cx43 alterations are modulated via the protein kinase C (PKC) signaling transduction pathway.

Methods

Oxyhemoglobin (OxyHb)-induced smooth muscle cells of basilar arterial and second-injection model in rat were used as CVS models in vitro and in vivo. In addition, dye transfer assays were used for gap junction-mediated intercellular communication (GJIC) observation in vitro and delayed cerebral ischemia (DCI) was observed in vivo by perfusion-weighted imaging (PWI) and intravital fluorescence microscopy.

Results

Increase in Cx43 mediated the development of SAH-induced CVS was found in both in vitro and in vivo CVS models. Enhanced GJIC was observed in vitro CVS model, this effect and increased Cx43 were reversed by preincubation with specific PKC inhibitors (chelerythrine or GF 109203X). DCI was observed in vivo on day 7 after SAH. However, DCI was attenuated by pretreatment with Cx43 siRNA or PKC inhibitors, and the increased Cx43 expression in vivo was also reversed by Cx43 siRNA or PKC inhibitors.

Conclusions

These data provide strong evidence that Cx43 plays an important role in CVS and indicate that changes in Cx43 expression may be mediated by the PKC pathway. The current findings suggest that Cx43 and the PKC pathway are novel targets for developing treatments for SAH-induced CVS.
Translational value of IDH1 and DNA methylation biomarkers in diagnosing lung cancers: a novel diagnostic panel of stage and histology-specificity
Authors: Zang Ruochuan , Wang Xinfeng , Jin Runsen , Lei Yuanyuan , Huang Jianbing , Liu Chengming , Zheng Sufei , Zhou Fang , Wu Qian , Sun Nan , Gao Shugeng , He Jie
Published: December 2019

Background

Lung cancer is the leading cause of cancer-related death worldwide, and the timely and serial assessment of low-dose computed tomography (LDCT) in high-risk populations remains a challenge. Furthermore, testing a single biomarker for the diagnosis of lung cancers is of relatively low effectiveness. Thus, a stronger diagnostic combination of blood biomarkers is needed to improve the diagnosis of non-small cell lung cancer (NSCLC).

Methods

The blood levels of individual biomarkers [IDH1, DNA methylation of short stature homeobox 2 gene (SHOX2), and prostaglandin E receptor 4 gene (PTGER4)] were measured and statistically analyzed in samples from healthy controls and patients with lung cancer. In total, 221 candidates were enrolled and randomly assigned into two groups for the training and validation of a diagnostic panel. Additionally, a subgroup analysis was performed in the whole cohort.

Results

A newly combined 3-marker diagnostic model for lung cancers was established and validated with area under the receiver operating characteristic (ROC) curve (AUC) values ranging from 0.835 to 0.905 in independent groups showing significantly stronger diagnostic value compared with a single tested biomarker. The sensitivity of the diagnostic model was as high as 86.1% and 80.0% in the training and validation sets, respectively. Although no apparent differences were found between the 3-marker and 2-marker models, the high clinical T-stage and histological type specificity of IDH1 and two other methylated DNA biomarkers were demonstrated in the subgroup analysis.

Conclusions

The combination of single biomarkers with high stage-specificity and histological type specificity (SHOX2 and PTGER4 DNA methylation and IDH1) showed better diagnostic performance in the detection of lung cancers compared with single marker assessment. A greater clinical utility of the panel may be developed by adding demographic/epidemiologic characteristics.
Development of 3D-printed myoelectric hand orthosis for patients with spinal cord injury
Authors: Yoo Hyun-Joon , Lee Sangbaek , Kim Jongheon , Park Chanki , Lee Boreom
Published: December 2019

Background

Spinal cord injury (SCI) is a severe medical condition affecting the hand and locomotor function. New medical technologies, including various wearable devices, as well as rehabilitation treatments are being developed to enhance hand function in patients with SCI. As three-dimensional (3D) printing has the advantage of being able to produce low-cost personalized devices, there is a growing appeal to apply this technology to rehabilitation equipment in conjunction with scientific advances. In this study, we proposed a novel 3D-printed hand orthosis that is controlled by electromyography (EMG) signals. The orthosis was designed to aid the grasping function for patients with cervical SCI. We applied this hand exoskeleton system to individuals with tetraplegia due to SCI and validated its effectiveness.

Methods

The 3D architecture of the device was designed using computer-aided design software and printed with a polylactic acid filament. The dynamic hand orthosis enhanced the tenodesis grip to provide sufficient grasping function. The root mean square of the EMG signal was used as the input for controlling the device. Ten subjects with hand weakness due to chronic cervical SCI were enrolled in this study, and their hand function was assessed before and after wearing the orthosis. The Toronto Rehabilitation Institute Hand Function Test (TRI-HFT) was used as the primary outcome measure. Furthermore, improvements in functional independence in daily living and device usability were evaluated.

Results

The newly developed orthosis improved hand function of subjects, as determined using the TRI-HFT (p < 0.05). Furthermore, participants obtained immediate functionality on eating after wearing the orthosis. Moreover, most participants were satisfied with the device as determined by the usability test. There were no side effects associated with the experiment.

Conclusions

The 3D-printed myoelectric hand orthosis was intuitive, easy to use, and showed positive effects in its ability to handle objects encountered in daily life. This study proved that combining simple EMG-based control strategies and 3D printing techniques was feasible and promising in rehabilitation engineering.

Trial registration

Clinical Research Information Service (CRiS), Republic of Korea. KCT0003995. Registered 2 May 2019 - Retrospectively registered.
Correction to: An optimised CRISPR/Cas9 protocol to create targeted mutations in homoeologous genes and an efficient genotyping protocol to identify edited events in wheat
Authors: Cui Xiucheng , Balcerzak Margaret , Schernthaner Johann , Babic Vivijan , Datla Raju , Brauer Elizabeth K. , Labbé Natalie , Subramaniam Rajagopal , Ouellet Thérèse
Published: December 2019

In the original publication [1], the copyright line was incorrectly published as “© The Author(s) 2019”. The corrected copyright line should read as “© Her Majesty the Queen in Right of Canada as represented by the Minister of Agriculture and Agri-Food Canada, 2019”. The original article has been corrected.
Topping-off surgery vs posterior lumbar interbody fusion for degenerative lumbar disease: a finite element analysis
Authors: Fan Yunpeng , Zhou Shaobo , Xie Tao , Yu Zefeng , Han Xiao , Zhu Liulong
Published: December 2019

Background

Adjacent segment disease (ASD) is a common complication after posterior lumbar interbody fusion (PLIF). Recently, a topping-off surgery (non-fusion with Coflex) has been developed to reduce the risk of ASD, yet whether and how the topping-off surgery can relieve ASD remains unclear. The purpose of this study was to explore the biomechanical effect of PLIF and Coflex on the adjacent segments via finite element (FE) analysis and discuss the efficacy of Coflex in preventing ASD.

Methods

A FE model of L3–L5 segments was generated based on the CT of a healthy volunteer via three commercially available software. Coflex and PLIF devices were modeled and implanted together with the segment model in the FE software. In the FE model, a pre-compressive load of 500 N, equal to two-thirds of the human body mass, was applied on the top surface of the L3. In addition, four types of moments (anteflexion, rear protraction, bending, and axial rotation) set as 10 Nm were successively applied to the FE model combined with this pre-compressive load. Then, the range of motion (ROM), the torsional rigidity, and the maximum von Mises equivalent stress on the L3–L4 intervertebral disc and the implant were analyzed.

Results

Both Coflex and PLIF reduced ROM. However, no significant difference was found in the maximum von Mises equivalent stress of adjacent segment disc between the two devices. Interestingly enough, both systems increased the torsional rigidity at the adjacent lumbar segment, and PLIF had a more significant increase. The Coflex implant had a larger maximum von Mises equivalent stress.

Conclusions

Both Coflex and PLIF reduced ROM at L3–L4, and thus improved the lumbar stability. Under the same load, both devices had almost the same maximum von Mises equivalent stress as the normal model on the adjacent intervertebral disc. But it is worthy to notice the torsional rigidity of PLIF was higher than that of Coflex, indicating that the lumbar treated with PLIF undertook a larger load to reach ROM of Coflex. Therefore, we presumed that ADS was related to a higher torsional rigidity.
The short- to midterm effectiveness of stemless prostheses compared to stemmed prostheses for patients who underwent total shoulder arthroplasty: a meta-analysis
Authors: Peng Wei , Ou Yufu , Wang Chenglong , Wei Jianxun , Mu Xiaoping , He Zhian
Published: December 2019

Background

To systematically compare the short- to midterm effectiveness of stemless prostheses to that of stemmed prostheses for patients who underwent total shoulder arthroplasty (TSA) and to provide a guideline for clinical decision-making.

Methods

PubMed, the Cochrane Library, and Web of Science were searched with the given search terms until July 2019 to identify published articles evaluating the clinical outcomes for stemless prostheses compared with stemmed prostheses for patients who underwent TSA. Data extraction and the quality assessment of the included studies were independently performed by two authors. Stata software 14.0 was used to analyze and synthesize the data.

Results

Two randomized controlled trials and six case-controlled studies with a total of 347 shoulders were included in this meta-analysis. The results of this meta-analysis showed that there were no significant differences between the stemless and stemmed prostheses in terms of the Constant score, pain score, strength, activities of daily living, postoperative range of motion (ROM), and postoperative maximum active ROM.

Conclusions

This is the first meta-analysis reporting the clinical results of stemless TSA in the short- to midterm follow-up period. Both types of shoulder prostheses were similar in achieving satisfactory clinical outcomes.
Exosomes derived from platelet-rich plasma present a novel potential in alleviating knee osteoarthritis by promoting proliferation and inhibiting apoptosis of chondrocyte via Wnt/β-catenin signaling pathway
Authors: Liu Xuchang , Wang Lubo , Ma Chengshan , Wang Guozong , Zhang Yuanji , Sun Shui
Published: December 2019

Background

Platelet-rich plasma (PRP) provides a nonsurgical approach for treating osteoarthritis (OA). Exosomes that play vital roles in intercellular communication have been studied extensively. Here, we investigated the therapeutic potential and molecular mechanism of exosomes derived from PRP (PRP-Exos) in alleviating OA.

Methods

Exosomes derived from PRP(PRP-Exos) were isolated and purified using the exoEasy Maxi Kit and then identified and analyzed. Primary rabbit chondrocytes were isolated and treated with interleukin 1 beta (IL-1β) to establish the OA model in vitro. Proliferation, migration, and apoptosis assays were measured and compared between PRP-Exos and activated PRP (PRP-As) to evaluate the therapeutic effects on OA. The mechanism involving the Wnt/β-catenin signaling pathway was investigated by Western blot analysis. In vivo, we established animal knee OA model by surgery to compare the therapeutic effect of PRP-Exos and PRP-As.

Results

We successfully isolated and purified exosomes from PRP using the exoEasy Maxi Kit. We also isolated and identified chondrocytes from the New Zealand white rabbit and established the IL-1β-induced OA model; meanwhile, PRP-Exos and PRP-As both inhibited the release of tumor necrosis factor-α(TNF-α) and there was no statistically significant difference between the two. In proliferation, migration, scratch assay, the promoting effect of PRP-Exos was significantly more better than PRP-As. Furthermore, PRP-Exos could significantly decreased apoptotic rate of OA chondrocyte compared with PRP-As. In Western blot analysis, the expression of β-catenin, and RUNX2, Wnt5a were increased in IL-1β-treated chondrocytes, but PRP-Exos and PRP-As could both reverse these changes, and the reversal effect of the former was better than the latter. In vivo, we found that both PRP-Exos and PRP-As displayed the progression of OA, and the effect of PRP-Exos was obviously better than PRP-As by chondrocyte count and Osteoarthritis Research Society International (OARSI) scoring system.

Conclusion

The therapeutic effects of PRP-Exos on OA were similar or better compared with those of PRP-As in vitro or in vivo. PRP-Exos acting as carriers containing growth factors derived from PRP present a novel therapy for OA by activating the Wnt/β-catenin signaling pathway.
Utilizing network pharmacology to explore the underlying mechanism of Radix Salviae in diabetic retinopathy
Authors: Piao Chun-Li , Luo Jin-Li , Jin De , Tang Cheng , Wang Li , Lian Feng-Mei , Tong Xiao-Lin
Published: December 2019

Introduction

Radix Salviae (Dan-shen in pinyin), a classic Chinese herb, has been extensively used to treat diabetic retinopathy in clinical practice in China for many years. However, the pharmacological mechanisms of Radix Salviae remain vague. The aim of this study was to decrypt the underlying mechanisms of Radix Salviae in the treatment of diabetic retinopathy using a systems pharmacology approach.

Methods

A network pharmacology-based strategy was proposed to elucidate the underlying multi-component, multi-target, and multi-pathway mode of action of Radix Salviae against diabetic retinopathy. First, we collected putative targets of Radix Salviae based on the Traditional Chinese Medicine System Pharmacology database and a network of the interactions among the putative targets of Radix Salviae and known therapeutic targets of diabetic retinopathy was built. Then, two topological parameters, “degree” and “closeness certainty” were calculated to identify the major targets in the network. Furthermore, the major hubs were imported to the Database for Annotation, Visualization and Integrated Discovery to perform a pathway enrichment analysis.

Results

A total of 130 nodes, including 18 putative targets of Radix Salviae, were observed to be major hubs in terms of topological importance. The results of pathway enrichment analysis indicated that putative targets of Radix Salviae mostly participated in various pathways associated with angiogenesis, protein metabolism, inflammatory response, apoptosis, and cell proliferation. The putative targets of Radix Salviae (vascular endothelial growth factor, matrix metalloproteinases, plasminogen, insulin-like growth factor-1, and cyclooxygenase-2) were recognized as active factors involved in the main biological functions of treatment, which implied that these were involved in the underlying mechanisms of Radix Salviae on diabetic retinopathy.

Conclusions

Radix Salviae could alleviate diabetic retinopathy via the molecular mechanisms predicted by network pharmacology. This research demonstrates that the network pharmacology approach can be an effective tool to reveal the mechanisms of traditional Chinese medicine from a holistic perspective.
The evolving therapeutic landscape of genetic skeletal disorders
Authors: Sabir Ataf Hussain , Cole Trevor
Published: December 2019

Background

Rare bone diseases account for 5% of all birth defects yet very few have personalised treatments. Developments in genetic diagnosis, molecular techniques and treatment technologies however, are leading to unparalleled therapeutic advance. This review explores the evolving therapeutic landscape of genetic skeletal disorders (GSDs); the key conditions and there key differentials.

Methods

A retrospective literature based review was conducted in December 2018 using a systematic search strategy for relevant articles and trials in Pubmed and clinicaltrials.gov respectively. Over 140 articles and 80 trials were generated for review.

Results

Over 20 personalised therapies are discussed in addition to several novel disease modifying treatments in over 25 GSDs. Treatments discussed are at different stages from preclinical studies to clinical trials and approved drugs, including; Burosumab for X-linked hypophosphatemia, Palovarotene for Hereditary Multiple Exostoses, Carbamazepine for Metaphyseal Chondrodysplasia (Schmid type), Lithium carbonate and anti-sclerostin therapy for Osteoporosis Pseudoglioma syndrome and novel therapies for Osteopetrosis. We also discuss therapeutic advances in Achondroplasia, Osteogenesis Imperfecta (OI), Hypophosphotasia (HPP), Fibrodysplasia Ossificans Progressiva, and RNA silencing therapies in preclinical studies for OI and HPP.

Discussion

It is an exciting time for GSD therapies despite the challenges of drug development in rare diseases. In discussing emerging therapies, we explore novel approaches to drug development from drug repurposing to in-utero stem cell transplants. We highlight the improved understanding of bone pathophysiology, genetic pathways and challenges of developing gene therapies for GSDs.
Violent conflict and breastfeeding: the case of Iraq
Authors: Diwakar Vidya , Malcolm Michael , Naufal George
Published: December 2019

Background

This study explores the relationship between armed conflict and breastfeeding practices of Iraqi mothers. To date, the relationship between violent conflict and breastfeeding is surprisingly understudied. Especially in the Middle East, which is conflict-prone and has a young population, research on war and household behavior is critical for promoting recovery and sustainable development.

Methods

This study employs a unique pairing of the Iraq Body Count Database and the 2006 and 2011 Multiple Indicator Cluster Surveys for Iraq. We use probit models to explore the association between armed conflict and several breastfeeding outcomes – whether a child was ever breastfed, whether a child was breastfed within 1 h after birth, whether a child is currently breastfed, and whether an infant under 6 months of age is exclusively breastfed. Our proxies for conflict intensity are the average rate of conflict-related casualties across the 3 years prior to survey administration and the rate of casualties averaged across the 2 years prior to the birth of the child, in the governorate in which the family resides. We employ a number of other independent variables important for breastfeeding status, including health controls and characteristics of the household, child and mother. We also use a Cox proportional hazards model to study the association between conflict and breastfeeding duration. We complement this analysis with various robustness checks, including disaggregation by year, controls for household wealth and an analysis of breastmilk substitutes and their potential for an interaction with household wealth.

Results

We find in our main results that increases in conflict-related casualties are associated with a significant decline in the probability that a child was ever breastfed and a decline in the probability that a child is currently breastfeeding. There is no significant association with exclusive breastfeeding or with initiation of breastfeeding within 1 h after birth. This result is robust to alternative measures of conflict, although some coefficients from estimation based on the 2006 subsample are positive and not significant, and reverse causation is a potential source of bias in interpreting cross-sectional feeding patterns. Results on breastfeeding duration are mixed. Our results also suggest an increase in the use of breastfeeding substitutes like formula concurrent to higher levels of conflict among wealthier households.

Conclusion

The results are informative in the context of designing policy aimed at stabilizing the long-term health and productivity of populations in conflict areas. Infant formula provided with the objective of offering temporary relief creates risks, including reducing the probability and duration of breastfeeding. Attention to the supply of health care and to support systems for women, especially skilled breastfeeding support and targeted support to infants dependent on formula, are matters of the utmost urgency during and after conflict periods.
CircNFIX promotes progression of glioma through regulating miR-378e/RPN2 axis
Authors: Ding Chenyu , Wu Zanyi , You Honghai , Ge Hongliang , Zheng Shufa , Lin Yuanxiang , Wu Xiyue , Lin Zhangya , Kang Dezhi
Published: December 2019

Background

Circular RNA nuclear factor I X (circNFIX) has been reported to play an important role in glioma progression. However, the mechanism by which circNFIX participates in glioma progression remains poorly understood.

Methods

GERIA online were used to analyze the abnormally expressed genes in glioma tissues. The expression levels of circNFIX, microRNA (miR)-378e and Ribophorin-II (RPN2) were measured by quantitative real-time polymerase chain reaction or western blot. Cell cycle distribution, apoptosis, glycolysis, migration and invasion were determined by flow cytometry, special kit and trans-well assays, respectively. The target association between miR-378e and circNFIX or RPN2 was confirmed by luciferase reporter assay, RNA immunoprecipitation and pull-down. Xenograft model was established to investigate the role of circNFIX in vivo.

Results

The expression of circNFIX was enhanced in glioma tissues and cells compared with matched controls and high expression of circNFIX indicated poor outcomes of patients. Knockdown of circNFIX led to arrest of cell cycle, inhibition of glycolysis, migration and invasion and promotion of apoptosis in glioma cells. circNFIX was a sponge of miR-378e. miR-378e overexpression suppressed cell cycle process, glycolysis, migration and invasion but promoted apoptosis. miR-378e silence abated the suppressive role of circNFIX knockdown in glioma progression. RPN2 as a target of miR-378e was positively regulated via circNFIX by competitively sponging miR-378e. Silencing circNFIX decreased glioma xenograft tumor growth by regulating miR-378e/RPN2 axis.

Conclusion

Knockdown of circNFIX inhibits progression of glioma in vitro and in vivo by increasing miR-378e and decreasing RPN2, providing a novel mechanism for understanding the pathogenesis of glioma.
Efficacy of Bimin decoction for patients with perennial allergic rhinitis: an open-label non-inferiority randomized controlled trial
Authors: Zhao Jingyi , Yan Xinyu , Gai Jianqing , Han Jinshuai , Zhang Hong , Luo Hui , Huang Shaoting , Wang Junge
Published: December 2019

Background

Allergic rhinitis (AR) is a common allergic disease. It affects people worldwide and traditional Chinese medicine is becoming popular among AR patients because it has a definite clinical effect and there are few adverse reactions. Lung qi deficiency and cold syndrome (LQDCS) is a frequent type of AR, and the Chinese herbal medicine bimin decoction (BMD) is prescribed for it. This study compared the clinical efficacy of BMD for AR patients with LQDCS to the conventional medicine loratadine and fluticasone nasal spray.

Methods

The study was an open-label non-inferiority randomized controlled trial. A total of 108 AR patients with LQDCS aged 19 to 60 were randomly allocated in a 1:1 ratio to the BMD group or the control group by the central computer system in Beijing Hospital of Traditional Chinese Medicine from January 2017 to April 2018. In total, 98 participants completed the study (BMD group n = 51 and control group n = 47). Patients in the BMD group received BMD while those in the control group received fluticasone nasal spray and loratadine tablets for 4 weeks. The primary outcome was the change in the Total Nasal Symptom Score (TNSS) between the baseline and the end of treatment. Changes in the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), nasal resistance, and acoustic rhinometry parameters were secondary outcomes. All side effects due to the treatments were recorded.

Results

After the 4-week treatment, the total TNSS was significantly reduced in both groups compared to the baseline (P <  0.05). No significant between-groups differences were observed for changes in TNSS scores [− 0.298 (95% confidence interval −0.640 to 0.140)], which was within the defined non-inferiority margin. RQLQ in both groups decreased significantly (P <  0.001) from baseline, though a more obvious reduction was observed for the BMD group (P <  0.001). There were no significant differences in nasal resistance, nasal volume, or nasal minimum cross-sectional area between groups after treatment (P > 0.05).

Conclusions

These findings indicate that BMD helps relieve the symptoms of perennial AR and improves rhinitis-related quality of life. Our study indicates that BMD is non-inferior to loratadine tablets and fluticasone nasal spray for AR patients with LQDCS.

Trial registration

Chinese Clinical Trial Registry, ChiCTR-INR-16010063. Registered on 2 December 2016.
Results and lessons learnt from a randomized controlled trial: prophylactic treatment of vestibular migraine with metoprolol (PROVEMIG)
Authors:   PROVEMIG investigators, Bayer Otmar , Adrion Christine , Al Tawil Amani , Mansmann Ulrich , Strupp Michael
Published: December 2019

Background

Vestibular migraine (VM) is the most frequent cause of recurrent spontaneous attacks of vertigo causally related to migraine. The objective of the Prophylactic treatment of vestibular migraine with metoprolol (PROVEMIG) trial was to demonstrate that metoprolol succinate is superior to placebo in the prevention of episodic vertigo- and migraine-related symptoms in patients with VM.

Methods

This phase III, two-arm, parallel-group, double-blind, randomized placebo-controlled trial was designed to be conducted at tertiary referral centres at neurology and ear, nose and throat departments of eight German university hospitals. The planned sample size was a total of 266 patients to be allocated. Adults aged 18 years or above diagnosed with probable or definitive VM according to the Neuhauser criteria 2001 were randomly assigned 1:1 to 6 months blinded metoprolol (maintenance dosage of 95 mg daily) or placebo. The primary efficacy outcome was the self-reported number of vertiginous attacks per 30 days documented by means of a paper-based daily symptom diary. The pre-specified time period of primary interest was defined as months 4 to 6. Secondary outcomes included the patient-reported number of migraine days and vertigo days, the Dizziness Handicap Inventory, and clinical assessments. Adverse events were reported throughout the whole 9-month study period.

Results

At the time of trial termination, no evidence for a difference in the incidence of vertiginous attacks between groups was detected. For the full analysis set, the incidence rate ratio was 0.983 (95% confidence interval (CI) 0.902–1.071) for metoprolol versus placebo. In both groups, there was a significant decline over time in the overall monthly vertigo attacks by a factor of 0.830 (95% CI 0.776–0.887). Results were consistent for all subjective and objective key measures of efficacy. The treatment was well tolerated with no unexpected safety findings.

Conclusions

After randomizing 130 patients PROVEMIG had to be discontinued because of poor participant accrual not related to the tolerability of the study medication or safety concerns; no treatment benefit of metoprolol over placebo could be established. Additional preparatory work is much needed in the development, psychometric evaluation and interpretation of clinically meaningful end points in trials on episodic syndromes like VM taking into consideration the complexity of this disease entity comprising two domains (vertigo- and headache-related disability).

Trial registration

EudraCT, 2009-013701-34. Prospectively registered on 8 April 2011.
Motor intervention with and without Nintendo® Wii for children with developmental coordination disorder: protocol for a randomized clinical trial
Authors: Cavalcante Neto Jorge Lopes , Steenbergen Bert , Tudella Eloisa
Published: December 2019

Background

Despite the benefits highlighted by motor interventions based on virtual reality for children with Developmental Coordination Disorder (DCD), there are still doubts as to whether these are greater than those obtained with conventional interventions due to the absence of systematized protocols, and lack of evidence. Here, we present a protocol to systematically compare the effects of two motor-training programs (one Nintendo® Wii-based and the other no-Wii motor activities) on the motor learning in children with DCD.

Methods/design

Two intervention protocols (one based on Nintendo® Wii and the other no-Wii motor activities) will be carried out, with interventions occurring twice a week in 60-min sessions, with a minimum of 12 and a maximum of 16 sessions per child.

The protocols were developed based on the domains of the Movement Assessment Battery for Children – Second Edition (MABC-2) (Manual Dexterity, Aiming and Catching, Balance), with two activities for each of the MABC − two domains. The study will include children aged 7 to 10 years with a total MABC-2 score ≤ 16, and a Developmental Coordination Disorder Questionnaire (DCDQ) score < 46 (age of 7 years), score < 55 (age group of 8 to 9 years and 11 months), or score < 57 (age of 10 years) as scored by the parents. Children will be randomly allocated by draw in one of the two intervention protocols. MABC-2 and DCDQ will be applied before and after intervention to evaluate the effects of the interventions on motor performance and parents’ perception, respectively. Motor learning will be assessed by means of the scores obtained in the games. Evaluators and therapists will be trained and evaluators will be blind regarding the data of the children in the study.

Discussion

Owing to its motivating aspects, training with Nintendo® Wii may be particularly beneficial for children with DCD. The results of this study protocol should help researchers and therapists to better understand the benefits of Nintendo® Wii-based motor intervention over those obtained with no-Wii interventions in children with DCD. It should also create references about more systematized protocols for replication in clinical practice, seeking the improvement of the motor components of these children.

Trial registration

RBR-89ydgj
Comparison of 22G standard and Franseen needles in endoscopic ultrasound-guided fine-needle aspiration for diagnosing pancreatic mass lesions: Study protocol for a controlled trial
Authors: Itonaga Masahiro , Yasukawa Satoru , Shimokawa Toshio , Takenaka Mamoru , Fukutake Nobuyasu , Ogura Takeshi , Sakagami Junichi , Shiomi Hideyuki , Okura Yasushi , Inatomi Osamu , Matsumoto Hisakazu , Kurita Akira , Suzuki Azumi , Tanaka Kiyohito , Kitano Masayuki
Published: December 2019

Background

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) was developed with the aim of further improving the diagnostic performance of endoscopic ultrasound. Although novel puncture needles have been specifically designed for collecting sufficient tissue specimens, clinical studies have indicated no clear difference in diagnostic performance between these novel needles and conventional puncture needles. Recently, a needle with Franseen geometry was developed specifically for EUS-FNA biopsy. Due to the characteristic shape of its tip, the Franseen needle is expected to be effective for scraping tissues, thus potentially increasing the diagnostic accuracy of EUS-FNA biopsy. We plan to carry out a prospective, multicenter, open-labeled, controlled trial to compare conventional and Franseen needles in terms of the diagnostic accuracy of EUS-FNA for evaluating the malignancy of pancreatic mass lesions.

Methods/design

The study will enroll 520 patients with pancreatic mass managed at any of 21 participating endoscopic centers. Lesion samples obtained using 22G conventional and Franseen needles will be assessed to compare the efficacy and safety of these two types of needles in EUS-FNA for evaluating the malignancy of mass lesions in the pancreas. Tissue samples will be fixed in formalin and processed for histologic evaluation. For the purpose of this study, only samples obtained with the first needle pass will be used for comparing the: (i) accuracy of the malignancy diagnosis, (ii) sensitivity and specificity for the malignancy diagnosis, (iii) procedure completion rate, (iv) sample cellularity, and (v) incidence of complications. Patient enrollment begins on July 17, 2018.

Discussion

The outcomes of this study may provide insight into the optimal needle choice for evaluating the malignancy of pancreatic solid lesions, thus aiding in the development of practice guidelines for pancreatic diseases.

Trial registration

University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR), UMIN000030634. Registered on 29 December 2017.

http://www.umin.ac.jp/

Version number: 01.2017.12.28.
Cerebral near-infrared spectroscopy monitoring versus treatment as usual for extremely preterm infants: a protocol for the SafeBoosC randomised clinical phase III trial
Authors: Hansen Mathias Lühr , Pellicer Adelina , Gluud Christian , Dempsey Eugene , Mintzer Jonathan , Hyttel-Sørensen Simon , Heuchan Anne Marie , Hagmann Cornelia , Ergenekon Ebru , Dimitriou Gabriel , Pichler Gerhard , Naulaers Gunnar , Cheng Guoqiang , Guimarães Hercilia , Tkaczyk Jakub , Kreutzer Karen B. , Fumagalli Monica , Claris Olivier , Lemmers Petra , Fredly Siv , Szczapa Tomasz , Austin Topun , Jakobsen Janus Christian , Greisen Gorm
Published: December 2019

Background

Cerebral oxygenation monitoring may reduce the risk of death and neurologic complications in extremely preterm infants, but no such effects have yet been demonstrated in preterm infants in sufficiently powered randomised clinical trials. The objective of the SafeBoosC III trial is to investigate the benefits and harms of treatment based on near-infrared spectroscopy (NIRS) monitoring compared with treatment as usual for extremely preterm infants.

Methods/design

SafeBoosC III is an investigator-initiated, multinational, randomised, pragmatic phase III clinical trial. Inclusion criteria will be infants born below 28 weeks postmenstrual age and parental informed consent (unless the site is using ‘opt-out’ or deferred consent). Exclusion criteria will be no parental informed consent (or if ‘opt-out’ is used, lack of a record that clinical staff have explained the trial and the ‘opt-out’ consent process to parents and/or a record of the parents’ decision to opt-out in the infant’s clinical file); decision not to provide full life support; and no possibility to initiate cerebral NIRS oximetry within 6 h after birth. Participants will be randomised 1:1 into either the experimental or control group. Participants in the experimental group will be monitored during the first 72 h of life with a cerebral NIRS oximeter. Cerebral hypoxia will be treated according to an evidence-based treatment guideline. Participants in the control group will not undergo cerebral oxygenation monitoring and will receive treatment as usual. Each participant will be followed up at 36 weeks postmenstrual age. The primary outcome will be a composite of either death or severe brain injury detected on any of the serial cranial ultrasound scans that are routinely performed in these infants up to 36 weeks postmenstrual age. Severe brain injury will be assessed by a person blinded to group allocation. To detect a 22% relative risk difference between the experimental and control group, we intend to randomise a cohort of 1600 infants.

Discussion

Treatment guided by cerebral NIRS oximetry has the potential to decrease the risk of death or survival with severe brain injury in preterm infants. There is an urgent need to assess the clinical effects of NIRS monitoring among preterm neonates.

Trial registration

ClinicalTrial.gov,NCT03770741. Registered 10 December 2018.
Effects of acupuncture on the hypothalamus-pituitary-adrenal axis in chronic insomnia patients: a study protocol for a randomized controlled trial
Authors: Liu Chengyong , Zheng Shiyu , Wu Wenzhong , Wang Xiaoqiu , Qin Shan , Zhao Yanan , Xi Hanqing , Wan Qingyun
Published: December 2019

Background

Acupuncture, as an important component of traditional Chinese medicine (TCM), has been widely applied in the treatment of chronic insomnia in China, while there is no clinical study related to its therapeutic mechanism.

Methods/design

A single-center, single-blind, randomized, placebo-controlled trial will be conducted at Jiangsu Hospital of Traditional Chinese Medicine. A total of 60 patients will be registered. Eligible participants will be randomly divided into acupuncture group and sham acupuncture group (n = 30 cases in each group). Patients in both groups will be treated once every other day, three times per week for 4 weeks. The primary outcome measures are Pittsburgh Sleep Quality Index (PSQI) and concentrations of adrenocorticotropic hormone (ATCH), corticotrophin-releasing hormone (CRH), and cortisol (CORT). Secondary outcome measures are Insomnia Severity Index (ISI) and Fatigue Severity Scale (FSS).

Discussion

This study aims to evaluate the therapeutic effects of acupuncture on chronic insomnia by using PSQI, ISI, and FSS. The mechanism of acupuncture on CIPs will be preliminarily discussed by analyzing the changes in concentrations of CRH, ACTH, and CORT before and after treatment.

Trial registration

Chinese Clinical Trials Register, ChiCTR1800020298.
Multicenter study of plastic vs. self-expanding metal stents in endoscopic ultrasound-guided drainage of walled-off pancreatic necrosis – PROMETHEUS: a randomized controlled trial protocol
Authors:   On behalf of the Spanish Working Group on Pancreatic Collection Therapy, Gornals Joan B. , Perez-Miranda Manuel , Vazquez-Sequeiros Enrique , Vila Juan , Esteban José M. , Gonzalez-Huix Ferran , Guarner-Argente Carlos , Sanchez-Yague Andres , Teran Alvaro , Bas-Cutrina Francesc , De La Serna Carlos , De Paredes Ana Garcia , Ballester Raquel , Velasquez-Rodriguez Julio , Salord Silvia , Tebe Cristian , Hereu Pilar , Videla Sebas
Published: December 2019

Background

It seems that lumen-apposing metal stents (LAMS) are displacing plastic stents in the therapy of pancreatic-fluid collection in walled-off necrosis (WON). To date, there is no quality of evidence to recommend LAMS as the standard treatment in the management of WON. The theoretical benefit of LAMS over plastic stents needs to be proven.

Methods/design

This is a randomized controlled, multicenter, prospective clinical trial with two parallel groups, without masking. One-hundred and fourteen patients with WON will undergo endoscopic ultrasound (EUS)-guided transmural draining in nine tertiary hospitals in Spain and will be randomized to the LAMS or plastic-stent group. The primary endpoint is the short-term (4 weeks) clinical success determined by the reduction of the collection (to < 50% or < 5 cm in size), along with clinical improvement. Secondary endpoints: long-term (4 months) clinical success (total resolution or 5 cm), procedure duration, level of difficulty, safety, and recurrences.

Discussion

The PROMETHEUS trial has been designed to determine whether LAMS are superior to plastic stents in EUS-guided transmural drainage of WON.

Trial registration

ClinicalTrials.gov, ID: NCT03100578. Registered on 4 April 2017. https://clinicaltrials.gov/ct2/home
Home parenteral nutrition with an omega-3-fatty-acid-enriched MCT/LCT lipid emulsion in patients with chronic intestinal failure (the HOME study): study protocol for a randomized, controlled, multicenter, international clinical trial
Authors: Klek Stanislaw , Chambrier Cécile , Cooper Sheldon C. , Gabe Simon , Kunecki Marek , Pironi Loris , Rahman Farooq , Sobocki Jacek , Szczepanek Kinga , Wanten Geert , Lincke Nicole , Glotzbach Bernhard , Forbes Alastair
Published: December 2019

Background

Home parenteral nutrition (HPN) is a life-preserving therapy for patients with chronic intestinal failure (CIF) indicated for patients who cannot achieve their nutritional requirements by enteral intake. Intravenously administered lipid emulsions (ILEs) are an essential component of HPN, providing energy and essential fatty acids, but can become a risk factor for intestinal-failure-associated liver disease (IFALD). In HPN patients, major effort is taken in the prevention of IFALD. Novel ILEs containing a proportion of omega-3 polyunsaturated fatty acids (n-3 PUFA) could be of benefit, but the data on the use of n-3 PUFA in HPN patients are still limited.

Methods/design

The HOME study is a prospective, randomized, controlled, double-blind, multicenter, international clinical trial conducted in European hospitals that treat HPN patients. A total of 160 patients (80 per group) will be randomly assigned to receive the n-3 PUFA-enriched medium/long-chain triglyceride (MCT/LCT) ILE (Lipidem/Lipoplus® 200 mg/ml, B. Braun Melsungen AG) or the MCT/LCT ILE (Lipofundin® MCT/LCT/Medialipide® 20%, B. Braun Melsungen AG) for a projected period of 8 weeks. The primary endpoint is the combined change of liver function parameters (total bilirubin, aspartate transaminase and alanine transaminase) from baseline to final visit. Secondary objectives are the further evaluation of the safety and tolerability as well as the efficacy of the ILEs.

Discussion

Currently, there are only very few randomized controlled trials (RCTs) investigating the use of ILEs in HPN, and there are very few data at all on the use of n-3 PUFAs. The working hypothesis is that n-3 PUFA-enriched ILE is safe and well-tolerated especially with regard to liver function in patients requiring HPN. The expected outcome is to provide reliable data to support this thesis thanks to a considerable number of CIF patients, consequently to broaden the present evidence on the use of ILEs in HPN.

Trial registration

ClinicalTrials.gov, ID:NCT03282955. Registered on 14 September 2017.
Efficacy of Actellic 300 CS-based indoor residual spraying on key entomological indicators of malaria transmission in Alibori and Donga, two regions of northern Benin
Authors: Salako Albert Sourou , Dagnon Fortune , Sovi Arthur , Padonou Gil Germain , Aïkpon Rock , Ahogni Idelphonse , Syme Thomas , Govoétchan Renaud , Sagbohan Herman , Sominahouin André Aimé , Akinro Bruno , Iyikirenga Laurent , Agossa Fiacre , Akogbeto Martin Codjo
Published: December 2019

Background

The current study shows the results of three years of IRS entomological monitoring (2016, before intervention; 2017 and 2018, after intervention) performed in Alibori and Donga, northern Benin.

Methods

Mosquito collections were performed on a monthly basis using human landing catches and pyrethrum spray catches in six districts including four treated with Actellic 300 CS (Kandi, Gogounou, Djougou and Copargo) and two untreated (Bembèrèkè and Kouandé) which served as control sites. Key transmission indicators of Anopheles gambiae (s.l.) as well as the residual activity of Actellic 300 CS assessed through WHO cone tests, were determined.

Results

The residual efficacy duration of Actellic 300 CS after the two IRS campaigns (2017 and 2018) was 4–5 months (May–September). The parity rate and the sporozoite index of An. gambiae (s.l.) were 36.62% and 0.71%, respectively, after the first spray round in treated areas compared to 57.24% and 3.7%, respectively, in the control areas (P < 0.0001). The same trend was observed after the second spray round. After the first spray round, each person received 1.6 infective bites/month (ib/m) in the treated areas against 12.11 ib/m in the control areas, resulting in a reduction rate of 86.78%. Similarly, the entomological inoculation rate was 1.5 ib/m after the second spray round in the treated areas vs 9.75 ib/m in the control areas, corresponding to a reduction of 84.61%. A decrease in the parity rate (46.26%), sporozoite index (85.75%) and EIR (87.27%) was observed for An. gambiae (s.l.) after the first round of IRS (June–October 2017) compared to the pre-intervention period (June–October 2016). The density of An. gambiae (s.l.) ranged between 0.38–0.48 per house in treated areas vs 1.53–1.76 An. gambiae (s.l.) per house respectively after the first and second IRS rounds.

Conclusions

This study showed the positive impact of IRS in reducing key entomological parameters of malaria transmission in Alibori and Donga. However, the considerable blood-feeding rate of An. gambiae (s.l.) in spray areas, stress the need for the population to sleep under long-lasting insecticidal nets (LLINs) in addition, to prevent from mosquito bites which did not succeed in resting on sprayed walls.