bluuebunny/crossref_metadata_2025 huggingface dataset:
Adolescents’ physical activity: cross-national comparisons of levels, distributions and disparities across 52 countries
Authors: Bann David , Scholes Shaun , Fluharty Meg , Shure Nikki
Published: December 2019

Background

Despite global concerns regarding physical inactivity, limited cross-national evidence exists to compare adolescents’ physical activity participation. We analysed data from 52 high- and low-middle income countries, with activity undertaken inside and outside of school in 2015. We investigated gender and socioeconomic disparities, and additionally examined correlations with country-level indices of physical education (PE) curriculum time allocation, wealth, and income inequality.

Methods

We compared adolescents’ reported activity levels inside and outside of school using nationally representative cross-sectional data from 52 high- and low-middle income countries (N = 347,935)—the Programme for International Student Assessment (PISA) in 2015. Students reported average attendance (days/week) in PE classes, and the days/week engaged in moderate activity (MPA) and vigorous activity (VPA) outside of school. We also compared gender and socioeconomic disparities, and additionally examined correlations with purported determinants—country-level estimates of PE curriculum time allocation, wealth, and income inequality.

Results

Average activity levels differed substantially both between and within regions, with potentially important differences in distributions identified—such as a bimodal distribution in the U.S. and Canada in PE. Males were more active than females, as were those from households with higher rather than lower household wealth; these disparities were modest for PE, but higher for moderate and vigorous activity outside school—there was strong evidence for heterogeneity in the magnitude of these disparities (e.g., I2 > 95% for gender differences across all countries). PE class attendance was positively correlated with PE curriculum time allocation (rho = 0.36); activity outcomes were inconsistently associated with country-level wealth and income inequality.

Conclusions

Our findings reveal extensive cross-country differences in adolescents’ physical activity; in turn, these highlight policy areas that could ultimately improve global adolescent health, such as the incorporation of minimum country-level PE classes, and the targeting of gender and socioeconomic disparities in activity conducted outside of school. Our findings also highlight the utility of educational databases such as PISA for use in global population health research.
Upregulation of mitotic bookmarking factors during enhanced proliferation of human stromal cells in human platelet lysate
Authors: Laner-Plamberger Sandra , Oeller Michaela , Mrazek Cornelia , Hartl Arnulf , Sonderegger Alina , Rohde Eva , Strunk Dirk , Schallmoser Katharina
Published: December 2019

Background

Innovative human stromal cell therapeutics require xeno-free culture conditions. Various formulations of human platelet lysate (HPL) are efficient alternatives for fetal bovine serum (FBS). However, a consistent lack of standardized manufacturing protocols and quality criteria hampers comparability of HPL-products. Aim of this study was to compare the biochemical composition of three differential HPL-preparations with FBS and to investigate their impact on stromal cell biology.

Methods

Stromal cells were isolated from bone marrow (BM), white adipose tissue (WAT) and umbilical cord (UC) and cultured in medium supplemented with pooled HPL (pHPL), fibrinogen-depleted serum-converted pHPL (pHPLS), mechanically fibrinogen-depleted pHPL (mcpHPL) and FBS. Biochemical parameters were analyzed in comparison to standard values in whole blood. Distinct growth factors and cytokines were measured by bead-based multiplex technology. Flow cytometry of stromal cell immunophenotype, in vitro differentiation, and mRNA expression analysis of transcription factors SOX2, KLF4, cMYC, OCT4 and NANOG were performed.

Results

Biochemical parameters were comparable in all pHPL preparations, but to some extent different to FBS. Total protein, glucose, cholesterol and Na+were elevated in pHPL preparations, K+and Fe3+levels were higher in FBS. Compared to FBS, pHPL-based media significantly enhanced stromal cell propagation. Characteristic immunophenotype and in vitro differentiation potential were maintained in all four culture conditions. The analysis of growth factors and cytokines revealed distinct levels depending on the pre-existence in pHPL, consumption or secretion by the stromal cells. Interestingly, mRNA expression of the transcription and mitotic bookmarking factors cMYC and KLF4 was significantly enhanced in a source dependent manner in stromal cells cultured in pHPL- compared to FBS-supplemented media. SOX2 mRNA expression of all stromal cell types was increased in all pHPL culture conditions.

Conclusion

All pHPL-supplemented media equally supported proliferation of WAT- and UC-derived stromal cells significantly better than FBS. Mitotic bookmarking factors, known to enable a quick re-entry to the cell cycle, were significantly enhanced in pHPL-expanded cells. Our results support a better characterization and standardization of humanized culture media for stromal cell-based medicinal products.
Applicability of duplex real time and lateral flow strip reverse-transcription recombinase aided amplification assays for the detection of Enterovirus 71 and Coxsackievirus A16
Authors: Li Xin-na , Shen Xin-xin , Li Ming-hui , Qi Ju-ju , Wang Rui-huan , Duan Qing-xia , Zhang Rui-qing , Fan Tao , Bai Xue-ding , Fan Guo-hao , Xie Yao , Ma Xue-jun
Published: December 2019

Background

Enterovirus 71 (EV71) and coxsackievirus A16 (CA16) are the two main etiological agents of Hand, Foot and Mouth Disease (HFMD). Simple and rapid detection of EV71 and CA16 is critical in resource-limited settings.

Methods

Duplex real time reverse-transcription recombinase aided amplification (RT-RAA) assays incorporating competitive internal amplification controls (IAC) and visible RT-RAA assays combined with lateral flow strip (LFS) for detection of EV71 and CA16 were developed respectively. Duplex real time RT-RAA assays were performed at 42 °C within 30 min using a portable real-time fluorescence detector, while LFS RT-RAA assays were performed at 42 °C within 30 min in an incubator. Recombinant plasmids containing conserved VP1 genes were used to analyze the sensitivities of these two methods. A total of 445 clinical specimens from patients who were suspected of being infected with HFMD were used to evaluate the performance of the assays.

Results

The limit of detection (LoD) of the duplex real time RT-RAA for EV71 and CA16 was 47 copies and 38 copies per reaction, respectively. The LoD of the LFS RT-RAA for EV71 and CA16 were both 91 copies per reaction. There was no cross reactivity with other enteroviruses. Compared to reverse transcription-quantitative PCR (RT-qPCR), the clinical diagnostic sensitivities of the duplex real time RT-RAA assay were 92.3% for EV71 and 99.0% for CA16, and the clinical diagnostic specificities were 99.7 and 100%, respectively. The clinical diagnostic sensitivities of the LFS RT-RAA assay were 90.1% for EV71 and 94.9% for CA16, and the clinical diagnostic specificities were 99.7 and 100%, respectively.

Conclusions

The developed duplex real time RT-RAA and LFS RT-RAA assays for detection of EV71 and CA16 are potentially suitable in primary clinical settings.
Marburg virus pathogenesis – differences and similarities in humans and animal models
Authors: Shifflett Kyle , Marzi Andrea
Published: December 2019

Marburg virus (MARV) is a highly pathogenic virus associated with severe disease and mortality rates as high as 90%. Outbreaks of MARV are sporadic, deadly, and often characterized by a lack of resources and facilities to diagnose and treat patients. There are currently no approved vaccines or treatments, and the chaotic and infrequent nature of outbreaks, among other factors, makes testing new countermeasures during outbreaks ethically and logistically challenging. Without field efficacy studies, researchers must rely on animal models of MARV infection to assess the efficacy of vaccines and treatments, with the limitations being the accuracy of the animal model in recapitulating human pathogenesis. This review will compare various animal models to the available descriptions of human pathogenesis and aims to evaluate their effectiveness in modeling important aspects of Marburg virus disease.
Implementation strategies for infection prevention and control promotion for nurses in Sub-Saharan Africa: a systematic review
Authors: Barrera-Cancedda Amy Elizabeth , Riman Kathryn A. , Shinnick Julianna E. , Buttenheim Alison M.
Published: December 2019

Background

Despite impressive reductions in infectious disease burden within Sub-Saharan Africa (SSA), half of the top ten causes of poor health or death in SSA are communicable illnesses. With emerging and re-emerging infections affecting the region, the possibility of healthcare-acquired infections (HAIs) being transmitted to patients and healthcare workers, especially nurses, is a critical concern. Despite infection prevention and control (IPC) evidence-based practices (EBP) to minimize the transmission of HAIs, many healthcare systems in SSA are challenged to implement them. The purpose of this review is to synthesize and critique what is known about implementation strategies to promote IPC for nurses in SSA.

Methods

The databases, PubMed, Ovid/Medline, Embase, Cochrane, and CINHAL, were searched for articles with the following criteria: English language, peer-reviewed, published between 1998 and 2018, implemented in SSA, targeted nurses, and promoted IPC EBPs. Further, 6241 search results were produced and screened for eligibility to identify implementation strategies used to promote IPC for nurses in SSA. A total of 61 articles met the inclusion criteria for the final review. The articles were evaluated using the Joanna Briggs Institute’s (JBI) quality appraisal tools. Results were reported using PRISMA guidelines.

Results

Most studies were conducted in South Africa (n = 18, 30%), within the last 18 years (n = 41, 67%), and utilized a quasi-experimental design (n = 22, 36%). Few studies (n = 14, 23%) had sample populations comprising nurses only. The majority of studies focused on administrative precautions (n = 36, 59%). The most frequent implementation strategies reported were education (n = 59, 97%), quality management (n = 39, 64%), planning (n = 33, 54%), and restructure (n = 32, 53%). Penetration and feasibility were the most common outcomes measured for both EBPs and implementation strategies used to implement the EBPs. The most common MAStARI and MMAT scores were 5 (n = 19, 31%) and 50% (n = 3, 4.9%) respectively.

Conclusions

As infectious diseases, especially emerging and re-emerging infectious diseases, continue to challenge healthcare systems in SSA, nurses, the keystones to IPC practice, need to have a better understanding of which, in what combination, and in what context implementation strategies should be best utilized to ensure their safety and that of their patients. Based on the results of this review, it is clear thatimplementationof IPC EBPs in SSA requires additional research from an implementation science-specific perspective to promote IPC protocols for nurses in SSA.
Comparative photon and proton dosimetry for patients with mediastinal lymphoma in the era of Monte Carlo treatment planning and variable relative biological effectiveness
Authors: Tseng Yolanda D. , Maes Shadonna M. , Kicska Gregory , Sponsellor Patricia , Traneus Erik , Wong Tony , Stewart Robert D. , Saini Jatinder
Published: December 2019

Background

Existing pencil beam analytical (PBA) algorithms for proton therapy treatment planning are not ideal for sites with heterogeneous tissue density and do not account for the spatial variations in proton relative biological effectiveness (vRBE). Using a commercially available Monte Carlo (MC) treatment planning system, we compared various dosimetric endpoints between proton PBA, proton MC, and photon treatment plans among patients with mediastinal lymphoma.

Methods

Eight mediastinal lymphoma patients with both free breathing (FB) and deep inspiration breath hold (DIBH) CT simulation scans were analyzed. The original PBA plans were re-calculated with MC. New proton plans that used MC for both optimization and dose calculation with equivalent CTV/ITV coverage were also created. A vRBE model, which uses a published model for DNA double strand break (DSB) induction, was applied on MC plans to study the potential impact of vRBE on cardiac doses. Comparative photon plans were generated on the DIBH scan.

Results

Re-calculation of FB PBA plans with MC demonstrated significant under coverage of the ITV V99 and V95. Target coverage was recovered by re-optimizing the PT plan with MC with minimal change to OAR doses. Compared to photons with DIBH, MC-optimized FB and DIBH proton plans had significantly lower dose to the mean lung, lung V5, breast tissue, and spinal cord for similar target coverage. Even with application of vRBE in the proton plans, the putative increase in RBE at the end of range did not decrease the dosimetric advantages of proton therapy in cardiac substructures.

Conclusions

MC should be used for PT treatment planning of mediastinal lymphoma to ensure adequate coverage of target volumes. Our preliminary data suggests that MC-optimized PT plans have better sparing of the lung and breast tissue compared to photons. Also, the potential for end of range RBE effects are unlikely to be large enough to offset the dosimetric advantages of proton therapy in cardiac substructures for mediastinal targets, although these dosimetric findings require validation with late toxicity data.
Antithrombotic drugs do not increase intraoperative blood loss in emergency gastrointestinal surgery: a single-institution propensity score analysis
Authors: Matsuoka Tadashi , Kobayashi Kenji , Lefor Alan Kawarai , Sasaki Junichi , Shinozaki Hiroharu
Published: December 2019

Background

The use of antithrombotic drugs is increasing with the aging population. Prior to elective procedures, antithrombotic drugs are often discontinued. For emergency procedures in patients taking antithrombotic drugs, their effect cannot be attenuated which may lead to an increased risk of hemorrhagic events. However, there are few studies showing increased intraoperative blood loss in patients taking antithrombotic drugs who undergo emergency gastrointestinal surgery. The aim of this study is to determine whether the use of antithrombotic agents increases intraoperative blood loss in emergency gastrointestinal surgery.

Methods

A retrospective review of patients who underwent emergency abdominal surgery between January 2013 and December 2017 was conducted. The primary outcome measure was intraoperative blood loss. Patients were divided into the antithrombotic drug group and a control group, and a propensity score was developed using multivariate logistic regression. We use 1:1 propensity score matching analysis to compare outcomes between the two groups.

Results

Of 1555 patients included in this study, 1184 patients, including 170 patients taking antithrombotic drugs, were eligible for propensity score matching analysis. A 1:1 matching yielded 117 well-balanced pairs. There was no statistically significant difference in intraoperative blood loss (antithrombotic drug group vs control group, median (interquartile): 60 (225–10) vs 100 (243–10) ml, p = 0.43).

Conclusions

This study suggests that antithrombotic drugs do not increase intraoperative blood loss in patients undergoing emergency gastrointestinal surgery. Emergency gastrointestinal surgery for patients currently taking antithrombotic drugs can be performed safely, and the use of antithrombotic drugs is not a reason to delay surgical intervention.
Targeting T cell malignancies using CAR-based immunotherapy: challenges and potential solutions
Authors: Fleischer Lauren C. , Spencer H. Trent , Raikar Sunil S.
Published: December 2019

Chimeric antigen receptor (CAR) T cell therapy has been successful in treating B cell malignancies in clinical trials; however, fewer studies have evaluated CAR T cell therapy for the treatment of T cell malignancies. There are many challenges in translating this therapy for T cell disease, including fratricide, T cell aplasia, and product contamination. To the best of our knowledge, no tumor-specific antigen has been identified with universal expression on cancerous T cells, hindering CAR T cell therapy for these malignancies. Numerous approaches have been assessed to address each of these challenges, such as (i) disrupting target antigen expression on CAR-modified T cells, (ii) targeting antigens with limited expression on T cells, and (iii) using third party donor cells that are either non-alloreactive or have been genome edited at the T cell receptor α constant (TRAC) locus. In this review, we discuss CAR approaches that have been explored both in preclinical and clinical studies targeting T cell antigens, as well as examine other potential strategies that can be used to successfully translate this therapy for T cell disease.
Musashi2 contributes to the maintenance of CD44v6+ liver cancer stem cells via notch1 signaling pathway
Authors: Wang Xiju , Wang Ronghua , Bai Shuya , Xiong Si , Li Yawen , Liu Man , Zhao Zhenxiong , Wang Yun , Zhao Yuchong , Chen Wei , Billiar Timothy R. , Cheng Bin
Published: December 2019

Background

Liver cancer stem cells (LCSCs) contribute to hepatocellular carcinoma (HCC) development, metastasis, and drug resistance. MSI2 and Notch1 signaling are involved in the maintenance of CSCs. However, it is unknown whether MSI2 and Notch1 are involved in the maintenance of CD44v6+ LCSCs. Therefore, we investigated the clinical significance and function of MSI2 and its relationship with Notch1 signaling in the maintenance of stemness properties in CD44v6+ LCSCs.

Methods

The expression of MSI2 and CD44v6 were detected by fresh specimens and a HCC tissue microarray. The tissue microarray containing 82 HCC samples was used to analyze the correlation between CD44v6 and MSI2. CD44v6+/− cells were isolated using microbeads sorting. We explored the roles of MSI2 and Notch1 signaling in CD44v6+ LCSCs by sphere formation assay, transwell assay, clone formation assay in vitro, and xenograft tumor models in vivo. A Notch RT2PCR Array, Co-immunoprecipitation, and RNA-immunoprecipitation were used to further investigate the molecular mechanism of MSI2 in activating Notch1 signaling.

Results

Here, we found MSI2 expression was positively correlated with high CD44v6 expression in HCC tissues, and further correlated with tumor differentiation. CD44v6+ cells isolated from HCC cell lines exhibited increased self-renewal, proliferation, migration and invasion, resistance to Sorafenib and tumorigenic capacity. Both MSI2 and Notch1 signaling were elevated in sorted CD44v6+ cells than CD44v6- cells and played essential roles in the maintenance of stemness of CD44v6+ LCSCs. Mechanically, MSI2 directly bound to Lunatic fringe (LFNG) mRNA and protein, resulting in Notch1 activation.

Conclusions

Our results demonstrated that MSI2 maintained the stemness of CD44v6+ LCSCs by activating Notch1 signaling through the interaction with LFNG, which could be a potential molecular target for stem cell-targeted therapy for liver cancer.
Does virtual reality reduce pain in pediatric patients? A systematic review
Authors: Iannicelli Anna Maria , Vito Daniele , Dodaro Concetta Anna , De Matteo Pasquale , Nocerino Rita , Sepe Angela , Raia Valeria
Published: December 2019

Virtual Reality (VR) as a tool for pain reduction is the research topic of several clinical trial for Randomized Controlled Trials despite its wide use in the daily clinical practice for non- pharmacological reduction of pain in some countries. At present, there are no published reviews of VR-efficacy of pain reduction in pediatric patients. That is why we made a systematic review of the efficacy of VR as a tool for pain reduction in children and adolescents. Electronic databases and gray literature published between 2014 and 2019 were analyzed. A total of 9 studies were eligible according to the established inclusion criteria. Results show that virtual reality is a valid tool for non-pharmacological pain reduction and that this approach is to be preferred to the standard reduction techniques currently in use. However, more studies using standardized experimental methodologies are needed to provide more systematic comparison and quantitative synthesis.
Defining benefit threshold for extracorporeal membrane oxygenation in children with sepsis—a binational multicenter cohort study
Authors:   on behalf of the Australian & New Zealand Intensive Care Society (ANZICS) Centre for Outcomes & Resource Evaluation (CORE) and the Australian & New Zealand Intensive Care Society (ANZICS) Paediatric Study Group, Schlapbach Luregn J. , Chiletti Roberto , Straney Lahn , Festa Marino , Alexander Daniel , Butt Warwick , MacLaren Graeme
Published: December 2019

Background

The surviving sepsis campaign recommends consideration for extracorporeal membrane oxygenation (ECMO) in refractory septic shock. We aimed to define the benefit threshold of ECMO in pediatric septic shock.

Methods

Retrospective binational multicenter cohort study of all ICUs contributing to the Australian and New Zealand Paediatric Intensive Care Registry. We included patients < 16 years admitted to ICU with sepsis and septic shock between 2002 and 2016. Sepsis-specific risk-adjusted models to establish ECMO benefit thresholds with mortality as the primary outcome were performed. Models were based on clinical variables available early after admission to ICU. Multivariate analyses were performed to identify predictors of survival in children treated with ECMO.

Results

Five thousand sixty-two children with sepsis and septic shock met eligibility criteria, of which 80 (1.6%) were treated with veno-arterial ECMO. A model based on 12 clinical variables predicted mortality with an AUROC of 0.879 (95% CI 0.864–0.895). The benefit threshold was calculated as 47.1% predicted risk of mortality. The observed mortality for children treated with ECMO below the threshold was 41.8% (23 deaths), compared to a predicted mortality of 30.0% as per the baseline model (16.5 deaths; standardized mortality rate 1.40, 95% CI 0.89–2.09). Among patients above the benefit threshold, the observed mortality was 52.0% (13 deaths) compared to 68.2% as per the baseline model (16.5 deaths; standardized mortality rate 0.61, 95% CI 0.39–0.92). Multivariable analyses identified lower lactate, the absence of cardiac arrest prior to ECMO, and the central cannulation (OR 0.31, 95% CI 0.10–0.98,p = 0.046) as significant predictors of survival for those treated with VA-ECMO.

Conclusions

This binational study demonstrates that a rapidly available sepsis mortality prediction model can define thresholds for survival benefit in children with septic shock considered for ECMO. Survival on ECMO was associated with central cannulation. Our findings suggest that a fully powered RCT on ECMO in sepsis is unlikely to be feasible.
Prophylactic use of levosimendan in pediatric patients undergoing cardiac surgery: a prospective randomized controlled trial
Authors: Wang Anbiao , Cui Chaomei , Fan Yiou , Zi Jie , Zhang Jie , Wang Guanglai , Wang Fang , Wang Jun , Tan Qi
Published: December 2019

Background

The administration of levosimendan prophylactically to patients undergoing cardiac surgery remains a controversial practice, and few studies have specifically assessed the value of this approach in pediatric patients. This study therefore sought to explore the safety and efficacy of prophylactic levosimendan administration to pediatric patients as a means of preventing low cardiac output syndrome (LCOS) based upon hemodynamic, biomarker, and pharmacokinetic readouts.

Methods

This was a single-center, double-blind, randomized, placebo-controlled trial. Patients ≤ 48 months old were enrolled between July 2018 and April 2019 and were randomly assigned to groups that received either placebo or levosimendan infusions for 48 h post-surgery, along with all other standard methods of care. LCOS incidence was the primary outcome of this study.

Results

A total of 187 patients were enrolled, of whom 94 and 93 received levosimendan and placebo, respectively. LCOS incidence did not differ significantly between the levosimendan and placebo groups (10 [10.6%] versus 18 [19.4%] patients, respectively; 95% confidence interval [CI] 0.19–1.13; p = 0.090) nor did 90-day mortality (3 [3.2%] versus 4 [4.3%] patients, CI 0.14–3.69, p = 0.693), duration of mechanical ventilation (median, 47.5 h and 39.5 h, respectively; p = 0.532), ICU stay (median, 114.5 h and 118 h, respectively; p = 0.442), and hospital stay (median, 20 days and 20 days, respectively; p = 0.806). The incidence of hypotension and cardiac arrhythmia did not differ significantly between the groups. Levels of levosimendan fell rapidly without any plateau in plasma concentrations during infusion. A multiple logistic regression indicated that randomization to the levosimendan group was a predictor of LCOS.

Conclusions

Prophylactic levosimendan administration was safe in pediatric patients and had some benefit to postoperative hemodynamic parameters, but failed to provide significant benefit with respect to LCOS or 90-day mortality relative to placebo.

Trial registration

Name of the registry: Safety evaluation and therapeutic effect of levosimendan on the low cardiac output syndrome in patients after cardiopulmonary bypass. Trial registration number: ChiCTR1800016594. Date of registration: 11 June 2018. URL of trial registry record: http://www.chictr.org.cn/index.aspx
Lasting s-ketamine block of spreading depolarizations in subarachnoid hemorrhage: a retrospective cohort study
Authors: Santos Edgar , Olivares-Rivera Arturo , Major Sebastian , Sánchez-Porras Renán , Uhlmann Lorenz , Kunzmann Kevin , Zerelles Roland , Kentar Modar , Kola Vasilis , Aguilera Adrian Hernández , Herrera Mildred Gutierrez , Lemale Coline L. , Woitzik Johannes , Hartings Jed A. , Sakowitz Oliver W. , Unterberg Andreas W. , Dreier Jens P.
Published: December 2019

Objective

Spreading depolarizations (SD) are characterized by breakdown of transmembrane ion gradients and excitotoxicity. Experimentally, N-methyl-d-aspartate receptor (NMDAR) antagonists block a majority of SDs. In many hospitals, the NMDAR antagonist s-ketamine and the GABAA agonist midazolam represent the current second-line combination treatment to sedate patients with devastating cerebral injuries. A pressing clinical question is whether this option should become first-line in sedation-requiring individuals in whom SDs are detected, yet the s-ketamine dose necessary to adequately inhibit SDs is unknown. Moreover, use-dependent tolerance could be a problem for SD inhibition in the clinic.

Methods

We performed a retrospective cohort study of 66 patients with aneurysmal subarachnoid hemorrhage (aSAH) from a prospectively collected database. Thirty-three of 66 patients received s-ketamine during electrocorticographic neuromonitoring of SDs in neurointensive care. The decision to give s-ketamine was dependent on the need for stronger sedation, so it was expected that patients receiving s-ketamine would have a worse clinical outcome.

Results

S-ketamine application started 4.2 ± 3.5 days after aSAH. The mean dose was 2.8 ± 1.4 mg/kg body weight (BW)/h and thus higher than the dose recommended for sedation. First, patients were divided according to whether they received s-ketamine at any time or not. No significant difference in SD counts was found between groups (negative binomial model using the SD count per patient as outcome variable, p = 0.288). This most likely resulted from the fact that 368 SDs had already occurred in the s-ketamine group before s-ketamine was given. However, in patients receiving s-ketamine, we found a significant decrease in SD incidence when s-ketamine was started (Poisson model with a random intercept for patient, coefficient − 1.83 (95% confidence intervals − 2.17; − 1.50), p < 0.001; logistic regression model, odds ratio (OR) 0.13 (0.08; 0.19), p < 0.001). Thereafter, data was further divided into low-dose (0.1–2.0 mg/kg BW/h) and high-dose (2.1–7.0 mg/kg/h) segments. High-dose s-ketamine resulted in further significant decrease in SD incidence (Poisson model, − 1.10 (− 1.71; − 0.49), p < 0.001; logistic regression model, OR 0.33 (0.17; 0.63), p < 0.001). There was little evidence of SD tolerance to long-term s-ketamine sedation through 5 days.

Conclusions

These results provide a foundation for a multicenter, neuromonitoring-guided, proof-of-concept trial of ketamine and midazolam as a first-line sedative regime.
Transcranial direct current stimulation in management of pain, mood, functionality, and quality of life in patients undergoing hemodialysis: a study protocol for a double-blind controlled randomized trial
Authors: Quintiliano Artur , Oehmen Tayanne , Kirsztajn Gianna Mastroianni , Pegado Rodrigo
Published: December 2019

Background

Persistent pain can lead to incapacitation requiring long-term pharmacological treatment. Up to 82% of chronic kidney disease (CKD) patients undergoing hemodialysis (HD) have chronic pain and most do not respond to usual medication. Advances in non-pharmacological treatments are necessary to promote pain relief without side effects and to restore functionality. Transcranial direct current stimulation (tDCS) promises to be a novel, cost-efficient, non-pharmacological treatment for CKD patients with chronic pain. In this study, we hypothesize that tDCS could improve pain, depression, functionality, and quality of life in patients with CKD undergoing HD.

Methods/design

We describe a single-center, parallel-design, double blind randomized, sham-controlled trial. Forty-five subjects with CKD undergoing HD will be randomized to a motor cortex (M1), a dorso lateral prefrontal cortex (DLPFC), or a sham group. A total of ten sessions will be administered to participants over 4 weeks using a monophasic continuous current with an intensity of 2 mA for 20 min. Participants will be evaluated at baseline, immediately after the tenth session, and at 1 week and 4 weeks of follow-up after the intervention. Pain, depression, functionality, and quality of life will be evaluated.

Discussion

The results from this study will provide initial clinical evidence on the efficacy and safety of tDCS in patients with CKD undergoing HD.

Trial registration

Brazilian Clinical Trials Registry/Registro Brasileiro de Ensaios Clínicos (ensaiosclinicos.gov.br), 1111–1216-0137. Registered on 20 June 2018.
A cognitive behavioral therapy intervention to reduce fear of hypoglycemia in young adults with type 1 diabetes (FREE): study protocol for a randomized controlled trial
Authors: Martyn-Nemeth Pamela , Duffecy Jennifer , Quinn Laurie , Park Chang , Mihailescu Dan , Penckofer Sue
Published: December 2019

Background

In persons with type 1 diabetes (T1D), hypoglycemia is the major limiting factor in achieving optimal glycemic control. All persons with T1D are at risk for hypoglycemia (blood glucose level < 70 mg/dl), which is life-threatening and accompanied by serious physical and psychological symptoms, resulting in profound fear of hypoglycemia (FOH) and reduced quality of life. Young adults with T1D are at risk for FOH and have worse glycemic control and self-management behavior than other age groups with T1D. FOH also results in increased glycemic variability (GV). A major gap exists in how to manage FOH. Our overall objective is to reduce FOH and improve diabetes self-management, glycemic control, and GV in young adults with T1D to reduce or delay diabetes complications and improve quality of life. We aim to (1) determine the feasibility and acceptability of an eight-week cognitive behavioral therapy (CBT)-based Fear Reduction Efficacy Evaluation (FREE) intervention in young adults with T1D who experience FOH; and (2) determine the impact of the FREE intervention, compared to an attention control group, on the outcomes FOH, self-management, glycemic control (A1C), and glycemic variability (continuous glucose monitoring recordings).

Methods/design

A randomized controlled trial in 50 young adults aged 18 to 35 years with T1D will be used. Eligible subjects will be randomized to the intervention program (Fear Reduction Efficacy Evaluation [FREE]) or attention control group. A one-week run-in phase is planned, with baseline measures of FOH, self-management behavior, A1C, and real-time continuous glucose monitoring recordings (RT-CGM) to calculate GV for both groups. The intervention group will participate in eight weekly individual one-hour sessions using CBT and exposure treatment for specific fears. RT-CGM and a daily FOH diary will be used as feedback cues as part of the FREE program. The attention control group will participate in eight weekly individual one-hour diabetes self-management education (DSME) sessions and wear a RT-CGM device (to measure GV only) over 8 weeks. At completion, FOH will be measured, and RT-CGM recordings will be analyzed to determine differences between the FREE and control groups.

Discussion

Findings from this proposed pilot study will serve as the foundation for a larger trial to reduce FOH and improve self-management, glycemic control, and GV.

Trial registration

ClinicalTrials.gov: A cognitive behavioral therapy (CBT) intervention to reduce fear of hypoglycemia in type 1 diabetes, NCT03549104. Registered June 7, 2018
Effects of perioperative transcutaneous electrical acupoint stimulation on monocytic HLA-DR expression in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass: study protocol for a double-blind randomized controlled trial
Authors: Chen Wen-ting , Wei Jin-feng , Wang Lan , Zhang Deng-wen , Tang Wei , Wang Jian , Yong Yue , Wang Jing , Zhou Ya-lan , Yuan Lan , Fu Guo-qiang , Wang Sheng , Song Jian-gang
Published: December 2019

Background

Cardiac surgery involving cardiopulmonary bypass (CPB) is known to be associated with a transient postoperative immunosuppression. When severe and persistent, this immune dysfunction predisposes patients to infectious complications, which contributes to a prolonged stay in the intensive care unit (ICU), and even mortality. Effective prevention and treatment methods are still lacking. Recent studies revealed that acupuncture-related techniques, such as electroacupuncture and transcutaneous electrical acupoint stimulation (TEAS), are able to produce effective cardioprotection and immunomodulation in adult and pediatric patients undergoing cardiac surgery with CPB, which leads to enhanced recovery. However, whether perioperative application of TEAS, a non-invasive technique, is able to improve immunosuppression of the patients with post-cardiosurgical conditions is unknown. Thus, as a preliminary study, the main objective is to evaluate the effects of TEAS on the postoperative expression of monocytic human leukocyte antigen (-D related) (mHLA-DR), a standardized “global” biomarker of injury or sepsis-associated immunosuppression, in patients receiving on-pump coronary artery bypass grafting (CABG).

Methods

This study is a single-center clinical trial. The 88 patients scheduled to receive CABG under CPB will be randomized into two groups: the group receiving TEAS, and the group receiving transcutaneous acupoint pseudo-electric stimulation (Sham TEAS). Expression of mHLA-DR serves as a primary endpoint, and other laboratory parameters (e.g., interleukin [IL]-6, IL-10) and clinical outcomes (e.g., postoperative infectious complications, ICU stay time, and mortality) as the secondary endpoints. In addition, immune indicators, such as high mobility group box 1 protein and regulatory T cells will also be measured.

Discussion

The current study is a preliminary monocentric clinical trial with a non-clinical primary endpoint, expression of mHLA-DR, aiming at determining whether perioperative application of TEAS has a potential to reverse CABG-associated immunosuppression. Although the immediate clinical impact of this study is limited, its results would inform further large-sample clinical trials using relevant patient-centered clinical outcomes as primary endpoints.

Trial registration

ClinicalTrials.gov, NCT02933996. Registered on 13 October 2016.
Can selenium deficiency in Malawi be alleviated through consumption of agro-biofortified maize flour? Study protocol for a randomised, double-blind, controlled trial
Authors: Joy Edward J. M. , Kalimbira Alexander A. , Gashu Dawd , Ferguson Elaine L. , Sturgess Joanna , Dangour Alan D. , Banda Leonard , Chiutsi-Phiri Gabriella , Bailey Elizabeth H. , Langley-Evans Simon C. , Lark R. Murray , Millar Kate , Young Scott D. , Matandika Limbanazo , Mfutso-Bengo Joseph , Phuka John C. , Phiri Felix P. , Gondwe Jellita , Ander E. Louise , Lowe Nicola M. , Nalivata Patson C. , Broadley Martin R. , Allen Elizabeth
Published: December 2019

Background

Micronutrient deficiencies including selenium (Se) are widespread in Malawi and potentially underlie a substantial disease burden, particularly among poorer and marginalised populations. Concentrations of Se in staple cereal crops can be increased through application of Se fertilisers – a process known as agronomic biofortification (agro-biofortification) – and this may contribute to alleviating deficiencies. The Addressing Hidden Hunger with Agronomy (AHHA) trial aims to establish the efficacy of this approach for improving Se status in rural Malawi.

Methods

A double-blind, randomised, controlled trial will be conducted in a rural community in Kasungu District, Central Region, Malawi. The hypothesis is that consumption of maize flour agro-biofortified with Se will increase serum Se concentration. We will recruit 180 women of reproductive age (WRA) (20–45 years) and 180 school-age children (SAC) (5–10 years) randomly assigned in a 1:1 ratio to receive either maize flour enriched through agro-biofortification with Se or a control flour not enriched with Se. Households will receive flour (330 g per capita per day) for 12 weeks. The primary outcome is Se concentration in serum (μg/L). Serum will be extracted from venous blood samples drawn at baseline (prior to flour distribution) and end-line. Selenium concentration will be measured by using inductively coupled plasma mass spectrometry.

Discussion

Findings will be communicated to policy stakeholders and participating communities and reported in peer-reviewed journals.

Trial registration

The Addressing Hidden Hunger with Agronomy (Malawi) trial is registered (5th March 2019; ISCRTN85899451).
Prospective randomized controlled trial comparing the efficacy and safety of Roux-en-Y gastric bypass and one-anastomosis gastric bypass (the RYSA trial): trial protocol and interim analysis
Authors: Saarinen Tuure , Meriläinen Sanna , Koivukangas Vesa , Pietiläinen Kirsi Hannele , Juuti Anne
Published: December 2019

Introduction

There is a lack of prospective studies comparing Roux-en-Y gastric bypass (RYGB) and one-anastomosis gastric bypass (OAGB). Also, the effects of bariatric surgery and weight loss need a deeper understanding through metabolic studies. We describe the trial protocol and interim analysis of a prospective randomized controlled study comparing RYGB and OAGB: the RYSA trial.

Materials and methods

In total, 120 bariatric patients will be randomized between RYGB and OAGB in two academic centers. All patients will be followed up for 10 years with analysis and measurements of weight, comorbidities, blood tests, body composition and questionnaires. Extensive metabolic analyses (mixed meal tests, energy expenditure, biopsies of muscle and subcutaneous fat, urine, saliva and fecal samples) will be carried out in the Obesity Research Unit, University of Helsinki, for all patients treated at the Helsinki University Hospital (80 patients) at baseline, 6 months and 12 months. Bile reflux will be studied for the OAGB group at the Helsinki University Hospital at 6 months with gastroscopy and scintigraphy.

Results

At an interim analysis at 3 months (half-way) through recruitment (30 RYGB and 30 OAGB patients) there have been no deaths and no intensive care unit admittances. One patient in both groups required additional gastroscopy, with anastomosis dilatation in the RYGB group but with no additional intervention in the OAGB group.

Conclusion

The trial can be safely carried out. Recruitment is estimated to be complete by the end of 2019.

Trial registration

Clinical Trials Identifier NCT02882685. Registered on August 30th 2016.
Zwakala Ndoda: a cluster and individually randomized trial aimed at improving testing, linkage, and adherence to treatment for hard-to reach men in KwaZulu-Natal, South Africa
Authors: van Rooyen Heidi , Makusha Tawanda , Joseph Phillip , Ngubane Thulani , Kulich Michal , Sweat Michael , Coates Thomas
Published: December 2019

Background

Men in sub-Saharan Africa are less likely than women to get tested for HIV, less likely to present for treatment, less likely to be maintained in treatment, more likely to have detectable viral load, more likely to transmit HIV with unprotected intercourse, and more likely to progress to AIDS and die sooner from HIV. The ultimate objective of this research is to provide evidence-based strategies to improve HIV testing and treatment of HIV-infected men.

Methods

This study is being conducted in the Greater Edendale Area and Vulindlela region in KwaZulu-Natal, South Africa. It is a two-stage design of a cluster-randomized trial and an individual randomized trial to test how structural and individual-level interventions address the demand-side factors that affect HIV testing and treatment for hard-to reach, high-risk men. It combines male-focused mobilization, community-based mobile HIV testing services, and a small incentive to determine if the strategies singly and in combination can result in more men diagnosed with HIV, and more men linked to and maintained in care with undetectable viral load.

Discussion

A priority for sub-Sahara Africa is developing and evaluating novel and cost-effective strategies for identifying hard-to-reach groups such as men, linking them to HIV testing and care services, and maintaining them in care to the point of viral suppression. We propose a combination prevention intervention that addresses men’s individual, interpersonal, and structural barriers to testing and care. This includes male-led mobilization to encourage uptake of testing and treatment, male-focused testing venues, male-only counselors, developing counseling models that are flexible and responsive to men, and strategies for adhering to clinic visits without missing work and navigating the healthcare system. By thoughtfully combining male-focused mobilization, and testing and addressing some of the barriers to male engagement with health facilities, this study hopes to add to the growing evidence base about how to reach, test, link, and maintain a hard-to-reach group such as men in HIV treatment and care services.

Trial registration

ClinicalTrials.gov, NCT03794245. Registered on 4 January 2019.
Treatment of hospital-acquired pneumonia with multi-drug resistant organism by Buzhong Yiqi decoction based on Fuzheng Quxie classical prescription: study protocol for a randomized controlled trial
Authors: Deng Dong , Chen Zhenyi , Jia Liyang , Bu Jianhong , Ye Miaoqing , Sun Lihua , Gen Yun , Zhang Wen , Chen Gang , Fang Bangjiang
Published: December 2019

Background

Drug resistance in China is becoming a more and more serious issue. Infection by drug-resistant bacteria has become a major disease that seriously threatens the health of Chinese people and affects national medical finance. Therefore, it is of great scientific and clinical significance to actively carry out research on the prevention and treatment of infections by multi-drug resistant organisms (MDRO). Previous studies by the authors suggested that patients with hospital-acquired pneumonia caused by MDRO mostly showed the pathological state of “insufficient healthy Qi and internal accumulation of pathogenic Qi” and “acute deficiency syndrome” mainly characterized by Qi deficiency. Buzhong Yiqi decoction is a famous classic prescription in traditional Chinese medicine (TCM) for treating internal damage fever. This study intends to provide an evidence-based rationale for Buzhong Yiqi decoction in treating MDRO hospital-acquired pneumonia by conducting a multi-center randomized controlled clinical study.

Methods/design

This study is designed to be a multi-center randomized controlled study in which patients are assigned randomly into control (standard therapy) and trial (standard therapy plus Buzhong Yiqi decoction) groups. The patients will be selected from the emergency department and the ICU inpatient department of five study sites and will all be diagnosed with MDRO hospital-acquired pneumonia and meet the inclusion criteria. Forty patients are to be enrolled in each study site, resulting in a total of 200 patients in the study. The treatment course is 28 days.

Discussion

In this study: (1) the theory of “acute Qi deficiency” in MDRO hospital-acquired pneumonia is put forward for the first time, and the basic theories of TCM are further improved; (2) a multi-center randomized controlled clinical study will be performed for the first time with Buzhong Yiqi decoction, the classic prescription for reinforcing healthy Qi and eliminating pathogenic Qi, providing a reliable evidence-based rationale for the treatment of MDRO pulmonary infection with TCM; (3) the clinical application and modern disease spectrum of Buzhong Yiqi decoction is expanded, and the scientific notion of “treating different diseases with the same method” is enriched further.

Trial registration

China Clinical Trial Registry, ChiCTR1900022429. Registered on April 11, 2019. http://www.chictr.org.cn/listbycreater.aspx.
Combining physical therapy and cognitive behavioral therapy techniques to improve balance confidence and community participation in people with unilateral transtibial amputation who use lower limb prostheses: a study protocol for a randomized sham-control clinical trial
Authors: Bourque McKenzie O. , Schneider Kristin L. , Calamari John E. , Reddin Christopher , Stachowiak Aaron , Major Matthew J. , Duncan Chad , Muthukrishnan Ranjini , Rosenblatt Noah J.
Published: December 2019

Background

Low balance confidence is a prevalent yet overlooked issue among people who use lower limb prostheses (LLP) that can diminish community integration and quality of life. There is a critical need to develop rehabilitation programs that specifically target balance confidence in people who use LLP. Previous research has shown that multicomponent interventions including cognitive-behavioral therapy (CBT) techniques and exercise are feasible and effective for improving balance confidence in older adults.

Therefore, a cognitive behavioral–physical therapy (CBPT) intervention was developed to target balance confidence and increase community integration in people who use LLP.

Methods/design

This randomized control trial will recruit 60 people who use LLP with low balance confidence. Participants will be randomized to the CBPT intervention condition or control condition.

Discussion

The trial is designed to test the effects of the CBPT intervention on balance confidence and functional mobility in lower limb prosthesis users by examining self-reported and objective measures of community integration and quality of life. The trial will also examine the relationship between changes in balance confidence and changes in community integration following participation in CBPT intervention. Additionally, through participant feedback, researchers will identify opportunities to improve intervention efficacy.

Trial registration

ClinicalTrials.gov, NCT03411148. Registration date: January 26, 2018.