bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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.
Monitoring adverse social and medical events in public health trials: assessing predictors and interpretation against a proposed model of adverse event reporting
Authors: Moody Gwenllian , Addison Katy , Cannings-John Rebecca , Sanders Julia , Wallace Carolyn , Robling Michael 
Published: December 2019

Abstract
Background
Although adverse event (AE) monitoring in trials focusses on medical events, social outcomes may be important in public or social care trials. We describe our approach to reporting and categorising medical and other AE reports, using a case study trial. We explore predictors of medical and social AEs, and develop a model for conceptualising safety monitoring.

Methods
The Building Blocks randomised controlled trial of specialist home visiting recruited 1618 first-time mothers aged 19 years or under at 18 English sites. Event reports collected during follow-up were independently reviewed and categorised as either Medical (standard Good Clinical Practice definition), or Social (trial-specific definition). A retrospectively developed system was created to classify AEs. Univariate analyses explored the association between baseline participant and study characteristics and the subsequent reporting of events. Factors significantly associated at this stage were progressed to binary logistic regressions to assess independent predictors.

Results
A classification system was derived for reported AEs that distinguished between Medical or Social AEs. One thousand, three hundred and fifteen event reports were obtained for mothers or their babies (1033 Medical, 257 Social). Allocation to the trial intervention arm was associated with increased likelihood of Medical rather than Social AE reporting. Poorer baseline psycho-social status predicted both Medical and Social events, and poorer psycho-social status better predicted Social rather than Medical events. Baseline predictors of Social AEs included being younger at recruitment (OR = 0.78 (CI = 0.67 to 0.90), p = 0.001), receiving benefits (OR = 1.60 (CI = 1.09 to 2.35), p = 0.016), and having a higher antisocial behaviour score (OR = 1.22 (CI = 1.09 to 1.36), p < 0.001). Baseline predictors of Medical AEs included having a limiting long-term illness (OR = 1.37 (CI = 1.01 to 1.88), p = 0.046), poorer mental health (OR = 1.03 (CI = 1.01 to 1.05), p = 0.004), and being in the intervention arm of the trial (OR = 1.34 (CI = 1.07 to 1.70), p = 0.012).

Conclusions
Continuity between baseline and subsequent adverse experiences was expected despite potentially beneficial intervention impact. We hypothesise that excess events reported for intervention-arm participants is likely attributable to surveillance bias. We interpreted our findings against a new model that explicates processes that may drive event occurrence, presentation and reporting. Focussing only upon Medical events may miss the well-being and social circumstances that are important for interpreting intervention safety and participant management.

Trial registration
ISRCTN, ID: ISRCTN23019866. Registered on 20 April 2009.
Microglia in the developing retina
Authors: Li Fenge , Jiang Danye , Samuel Melanie A. 
Published: December 2019

AbstractMicroglia are increasingly shown to be key players in neuron development and synapse connectivity. However, the underlying mechanisms by which microglia regulate neuron function remain poorly understood in part because such analysis is challenging in the brain where neurons and synapses are intermingled and connectivity is only beginning to be mapped. Here, we discuss the features and function of microglia in the ordered mammalian retina where the laminar organization of neurons and synapses facilitates such molecular studies. We discuss microglia origins and consider the evidence for molecularly distinct microglia subpopulations and their potential for differential roles with a particular focus on the early stages of retina development. We then review the models and methods used for the study of these cells and discuss emerging data that link retina microglia to the genesis and survival of particular retina cell subtypes. We also highlight potential roles for microglia in shaping the development and organization of the vasculature and discuss cellular and molecular mechanisms involved in this process. Such insights may help resolve the mechanisms by which retinal microglia impact visual function and help guide studies of related features in brain development and disease.