bluuebunny/crossref_metadata_2025_split huggingface dataset:
A randomized comparison of health-related quality of life outcomes of dolutegravir versus efavirenz-based antiretroviral treatment initiated in the third trimester of pregnancy
Authors: Ochanda Perez Nicholas , Lamorde Mohammed , Kintu Kenneth , Wang Duolao , Chen Tao , Malaba Thokozile , Myer Landon , Waitt Catriona , Reynolds Helen , Khoo Saye 
Published: June 2022

Abstract
Introduction
Evidence on health-related quality of life (HRQoL) outcomes is limited for new antiretroviral therapies (ART). Dolutegravir-based treatment is being rolled out as the preferred first-line treatment for HIV in many low- and middle-income countries. We compared HRQoL between treatment-naïve pregnant women randomized to dolutegravir- or efavirenz-based ART in a clinical trial in Uganda and South Africa.

Methods
We gathered HRQoL data from 203 pregnant women of mean age 28 years, randomized to either dolutegravir- or efavirenz-based ART. We used the medical outcomes study-HIV health survey at baseline, 24 and 48 weeks between years 2018 and 2019. Physical health summary (PHS) and mental health summary (MHS) scores were the primary study outcomes, while the 11 MOS-HIV subscales were secondary outcomes. We applied mixed model analysis to estimate differences within and between-treatment groups. Multivariate regression analysis was included to identify associations between primary outcomes and selected variables.

Results
At 24 weeks postpartum, HRQoL scores increased from baseline in both treatment arms: PHS (10.40, 95% CI 9.24, 11.55) and MHS (9.23, 95% CI 7.35, 11.10) for dolutegravir-based ART; PHS (10.24, 95% CI 9.10, 11.38) and MHS (7.54, 95% CI 5.66, 9.42) for efavirenz-based ART. Increased scores for all secondary outcomes were significant at p < 0.0001. At 48 weeks, improvements remained significant for primary outcomes within group comparison. Estimated difference in PHS were higher in the dolutegravir-based arm, while increases in MHS were more for women in the efavirenz-based armat 24 and 48 weeks. No significant differences were noted for corresponding PHS scores at these time points compared between groups. Differences between arms were observed in two secondary outcomes: role function (1.11, 95% CI 0.08, 2.13), p = 0.034 and physical function outcomes (2.97, 95% CI 1.20, 4.73), p = 0.001. In the multivariate analysis, internet access was associated with higher PHS scores while owning a bank account, using the internet and longer treatment duration were associated with an increase in MHS scores.

Conclusion
We found no important differences in HRQoL outcomes among HIV-positive women started on dolutegravir relative to efavirenz in late pregnancy. Increases in HRQoL in the first year after delivery provide additional support for the initiation of ART in HIV-positive women presenting late in pregnancy.
Trial Registration Clinical Trial Number: NCT03249181
Floating EMG sensors and stimulators wirelessly powered and operated by volume conduction for networked neuroprosthetics
Authors: Becerra-Fajardo Laura , Krob Marc Oliver , Minguillon Jesus , Rodrigues Camila , Welsch Christine , Tudela-Pi Marc , Comerma Albert , Oliveira Barroso Filipe , Schneider Andreas , Ivorra Antoni 
Published: June 2022

Abstract
Background
Implantable neuroprostheses consisting of a central electronic unit wired to electrodes benefit thousands of patients worldwide. However, they present limitations that restrict their use. Those limitations, which are more adverse in motor neuroprostheses, mostly arise from their bulkiness and the need to perform complex surgical implantation procedures. Alternatively, it has been proposed the development of distributed networks of intramuscular wireless microsensors and microstimulators that communicate with external systems for analyzing neuromuscular activity and performing stimulation or controlling external devices. This paradigm requires the development of miniaturized implants that can be wirelessly powered and operated by an external system. To accomplish this, we propose a wireless power transfer (WPT) and communications approach based on volume conduction of innocuous high frequency (HF) current bursts. The currents are applied through external textile electrodes and are collected by the wireless devices through two electrodes for powering and bidirectional digital communications. As these devices do not require bulky components for obtaining power, they may have a flexible threadlike conformation, facilitating deep implantation by injection.

Methods
We report the design and evaluation of advanced prototypes based on the above approach. The system consists of an external unit, floating semi-implantable devices for sensing and stimulation, and a bidirectional communications protocol. The devices are intended for their future use in acute human trials to demonstrate the distributed paradigm. The technology is assayed in vitro using an agar phantom, and in vivo in hindlimbs of anesthetized rabbits.

Results
The semi-implantable devices were able to power and bidirectionally communicate with the external unit. Using 13 commands modulated in innocuous 3 MHz HF current bursts, the external unit configured the sensing and stimulation parameters, and controlled their execution. Raw EMG was successfully acquired by the wireless devices at 1 ksps.

Conclusions
The demonstrated approach overcomes key limitations of existing neuroprostheses, paving the way to the development of distributed flexible threadlike sensors and stimulators. To the best of our knowledge, these devices are the first based on WPT by volume conduction that can work as EMG sensors and as electrical stimulators in a network of wireless devices.
Molecular cytogenetic analysis of partial monosomy 10p and trisomy 10q resulting from familial pericentric inversion (10): a first case report in Chinese population
Authors: Zhuang Jianlong , Chen Chunnuan , Huang Rongfu , Luo Qi , Jiang Yuying , Zeng Shuhong , Wang Yuanbai , Xie Yingjun 
Published: June 2022

Abstract
Background
Chromosome aberrations of 10p monosomy and 10q trisomy resulting from parental pericentric inversion 10 are extremely rare, and to date, very few reports have been published on the matter.

Case Presentation
A 30-year-old pregnant woman with recurrent pregnancy loss is enrolled in this research. In this pregnancy, spontaneous abortion occurred in the first trimester of her pregnancy. Chromosomal microarray analysis of the abortion tissue showed a partial 10p monosomy (arr[GRCh37] 10p15.3p11.21(100,047_34,848,853) × 1) and a duplication of 10q (arr[GRCh37] 10q26.13q26.3(126,093,990_135,426,386) × 3). Further parental karyotype analysis indicated that the chromosomal abnormalities in the fetus was resulted from paternal pericenric inversion inv(10)(p11.21q26.13). This study presents the first case of a large deletion of 10p combined with 10q trisomy, resulting in pregnancy loss. Of these two manifestations, the large deletion of chromosome 10p may be the primary reason for spontaneous abortion in this subject.

Conclusions
This study presents the first case of partial 10p monosomy associated with 10q trisomy in Chinese population. It provides more information on the chromosome aberration of 10p monosomy and 10q trisomy and further strengthens the application value of microarray in the molecular etiological diagnosis of recurrent spontaneous abortion.
Baseline plasma IL-18 may predict simvastatin treatment response in patients with ARDS: a secondary analysis of the HARP-2 randomised clinical trial
Authors: Boyle Andrew James , Ferris Peter , Bradbury Ian , Conlon John , Shankar-Hari Manu , Rogers Angela J. , O’Kane Cecilia M. , McAuley Daniel F. 
Published: June 2022

Abstract
Background
Interleukin (IL)-18 is a marker of inflammasome activation, and high baseline plasma IL-18 is associated with increased mortality in patients with sepsis-induced ARDS. The aim of this analysis was to determine if simvastatin was associated with benefit in patients with ARDS and high plasma IL-18.

Methods
In this secondary analysis of the HARP-2 study, we compared 28-day mortality and response to simvastatin according to baseline plasma IL-18 using cox proportional hazards analysis. Separately, monocyte-derived macrophages from healthy volunteers were pre-incubated with simvastatin or rosuvastatin before stimulation with ATP and LPS, and the effect on secreted IL-18 and IL-1β compared.

Results
511 patients from HARP-2 had available data. High baseline plasma IL-18 (≥ 800 pg/ml) was associated with increased 28-day mortality (high IL-18 30.6% vs. low IL-18 17.5%; HR 1.89 [95% CI 1.30–2.73]; p = 0.001). Allocation to simvastatin in patients with high baseline plasma IL-18 was associated with a lower probability of 28-day mortality compared with placebo (24.0% vs 36.8%; p = 0.01). Finally, simvastatin, but not rosuvastatin, reduced stimulated macrophage secretion of IL-18 and IL-1β.

Conclusion
In patients with high baseline plasma IL-18, simvastatin is associated with a higher probability of survival, and this effect may be due to reduced inflammasome activation. These data suggest that baseline plasma IL-18 may allow a personalised treatment approach by identifying patients with ARDS who could benefit from simvastatin therapy.
Early intubation and patient-centered outcomes in septic shock: a secondary analysis of a prospective multicenter study
Authors: Mellado-Artigas Ricard , Ferrando Carlos , Martino Frédéric , Delbove Agathe , Ferreyro Bruno L. , Darreau Cedric , Jacquier Sophie , Brochard Laurent , Lerolle Nicolas 
Published: June 2022

Abstract
Purpose
Despite the benefits of mechanical ventilation, its use in critically ill patients is associated with complications and had led to the growth of noninvasive techniques. We assessed the effect of early intubation (first 8 h after vasopressor start) in septic shock patients, as compared to non-early intubated subjects (unexposed), regarding in-hospital mortality, intensive care and hospital length of stay.

Methods
This study involves secondary analysis of a multicenter prospective study. To adjust for baseline differences in potential confounders, propensity score matching was carried out. In-hospital mortality was analyzed in a time-to-event fashion, while length of stay was assessed as a median difference using bootstrapping.

Results
A total of 735 patients (137 intubated in the first 8 h) were evaluated. Propensity score matching identified 78 pairs with similar severity and characteristics on admission. Intubation was used in all patients in the early intubation group and in 27 (35%) subjects beyond 8 h in the unexposed group. Mortality occurred in 35 (45%) and in 26 (33%) subjects in the early intubation and unexposed groups (hazard ratio 1.44 95% CI 0.86–2.39, p = 0.16). ICU and hospital length of stay were not different among groups [9 vs. 5 (95% CI 1 to 7) and 14 vs. 16 (95% CI − 7 to 8) days]. All sensitivity analyses confirmed the robustness of our findings.

Conclusions
An early approach to invasive mechanical ventilation did not improve outcomes in this matched cohort of patients. The limited number of patients included in these analyses out the total number included in the study may limit generalizability of these findings.
Trial registration NCT02780466. Registered on May 19, 2016.
Dissection of multiple sclerosis genetics identifies B and CD4+ T cells as driver cell subsets
Authors: Guo Michael H. , Sama Prashanth , LaBarre Brenna A. , Lokhande Hrishikesh , Balibalos John , Chu Ci , Du Xiaomi , Kheradpour Pouya , Kim Charles C. , Oniskey Taylor , Snyder Thomas , Soghoian Damien Z. , Weiner Howard L. , Chitnis Tanuja , Patsopoulos Nikolaos A. 
Published: June 2022

Abstract
Background
Multiple sclerosis (MS) is an autoimmune condition of the central nervous system with a well-characterized genetic background. Prior analyses of MS genetics have identified broad enrichments across peripheral immune cells, yet the driver immune subsets are unclear.

Results
We utilize chromatin accessibility data across hematopoietic cells to identify cell type-specific enrichments of MS genetic signals. We find that CD4 T and B cells are independently enriched for MS genetics and further refine the driver subsets to Th17 and memory B cells, respectively. We replicate our findings in data from untreated and treated MS patients and find that immunomodulatory treatments suppress chromatin accessibility at driver cell types. Integration of statistical fine-mapping and chromatin interactions nominate numerous putative causal genes, illustrating complex interplay between shared and cell-specific genes.

Conclusions
Overall, our study finds that open chromatin regions in CD4 T cells and B cells independently drive MS genetic signals. Our study highlights how careful integration of genetics and epigenetics can provide fine-scale insights into causal cell types and nominate new genes and pathways for disease.
INSPIRA: study protocol for a randomized-controlled trial about the effect of spirometry-assisted preoperative inspiratory muscle training on postoperative complications in abdominal surgery
Authors: Birrer D. L. , Kuemmerli C. , Obwegeser A. , Liebi M. , von Felten S. , Pettersson K. , Horisberger K. 
Published: June 2022

Abstract
Background
Rehabilitation strategies after abdominal surgery enhance recovery and improve outcome. A cornerstone of rehabilitation is respiratory physiotherapy with inspiratory muscle training to enhance pulmonary function.
Pre-habilitation is the process of enhancing functional capacity before surgery in order to compensate for the stress of surgery and postoperative recovery. There is growing interest in deploying pre-habilitation interventions prior to surgery.
The aim of this study is to assess the impact of preoperative inspiratory muscle training on postoperative overall morbidity. The question is, whether inspiratory muscle training prior to elective abdominal surgery reduces the number of postoperative complications and their severity grade.

Methods
We describe a prospective randomized-controlled single-centre trial in a tertiary referral centre. The primary outcome is the Comprehensive Complication Index (CCI) at 90 days after surgery. The CCI expresses morbidity on a continuous numeric scale from 0 (no complication) to 100 (death) by weighing all postoperative complications according to the Clavien-Dindo classification for their respective severity.
In the intervention group, patients will be instructed by physiotherapists to perform inspiratory muscle training containing of 30 breaths twice a day for at least 2 weeks before surgery using Power®Breathe KHP2. Depending on the surgical schedule, training can be extended up to 6 weeks. In the control group, no preoperative inspiratory muscle training will be performed. After the operation, both groups receive the same physiotherapeutic support.

Discussion
Existing data about preoperative inspiratory muscle training on postoperative complications are ambiguous and study protocols are often lacking a clear design and a clearly defined endpoint. Most studies consist of multi-stage concepts, comprehensively supervised and long-term interventions, whose implementation in clinical practice is hardly possible. There is a clear need for randomized-controlled studies with a simple protocol that can be easily transferred into clinical practice. This study examines the effortless adjustment of the common respiratory physiotherapy from currently postoperative to preoperative. The external measurement by the device eliminates the diary listing of patients’ performances and allows the exercise adherence and thus the effect to be objectively recorded.

Trial registration
ClinicalTrials.govNCT04558151. Registered on September 15, 2020.
E-HEalth treatment in Long-term Dialysis (E-HELD): study protocol for a multicenter randomized controlled trial evaluating personalized Internet-based cognitive-behavioral therapy in dialysis patients
Authors: Tommel Judith , Evers Andrea W. M. , van Hamersvelt Henk W. , van Dijk Sandra , Chavannes Niels H. , Wirken Lieke , Hilbrands Luuk B. , van Middendorp Henriët 
Published: June 2022

Abstract
Background
Kidney failure and dialysis treatment have a large impact on a patient’s life. Patients experience numerous, complex symptoms and usually have multiple comorbid conditions. Despite the multitude of problems, patients often have priorities for improvement of specific aspects of their functioning, which would be helpful for clinicians to become informed of. This highlights a clear need for patient-centered care in this particular patient group, with routine screening as a vital element to timely recognize symptoms and tailored treatment to match individual patients’ needs and priorities. By also providing feedback on patient’s screening results to the patient itself, the patient is empowered to actively take control in one’s mostly uncontrollable disease process. The current paper describes the study design of a multicenter randomized controlled trial evaluating the effectiveness of the “E-HEealth treatment in Long-term Dialysis” (E-HELD) intervention. This therapist-guided Internet-based cognitive-behavioral therapy (ICBT) intervention is focused on and personalized to the myriad of problems that dialysis patients experience and prioritize.

Methods
After a screening procedure on adjustment problems, 130 eligible dialysis patients will be randomized to care as usual or the E-HELD intervention. Patients will complete questionnaires on distress (primary outcome measure), several domains of functioning (e.g., physical, psychological, social), potential predictors and mediators of treatment success, and the cost-effectiveness of the intervention, at baseline, 6-month follow-up, and 12-month follow-up. In addition, to take account of the personalized character of the intervention, the Personalized Priority and Progress Questionnaire (PPPQ) will be administered which is a personalized instrument to identify, prioritize, and monitor individual problems over time.

Discussion
The present study design will provide insight in the effectiveness of tailored ICBT in patients with kidney failure who are treated with dialysis. When proven effective, the screening procedure and the subsequent ICBT intervention could be implemented in routine care to detect, support, and treat patients struggling with adjustment problems.

Trial registration
NL63422.058.17 [Registry ID: METC-LDD]
NL7160 [Netherlands Trial Register; registered on 16 July 2018]
Keeping up with the guidelines: design changes to the STREAM stage 2 randomised controlled non-inferiority trial for rifampicin-resistant tuberculosis
Authors: Goodall Ruth L. , Sanders Karen , Bronson Gay , Gurumurthy Meera , Torrea Gabriela , Meredith Sarah , Nunn Andrew , Rusen I. D. ,   on behalf of the STREAM Trial Team, Bronson Gay , Gurumurthy Meera , Komrska Jan , Patel Leena , Qawiy Ishmael , Rusen I. D. , Ali Sonia , Bellenger Katharine , Bennet Deborah , Bennet Rachel , Dodds Wendy , Goodall Ruth , Meredith Sarah , Murphy Brendan , Nunn Andrew , Roach Carol , Sanders Karen , Whitney Johanna , Van Deun Armand , Torrea Gabriela , Chiang Chen-Yuan , Rosu Laura , Squire Bertie , Madan Jason 
Published: June 2022

AbstractResults from the STREAM stage 1 trial showed that a 9-month regimen for patients with rifampicin-resistant tuberculosis was non-inferior to the 20-month regimen recommended by the 2011 WHO treatment guidelines. Similar levels of severe adverse events were reported on both regimens suggesting the need for further research to optimise treatment. Stage 2 of STREAM evaluates two additional short-course regimens, both of which include bedaquiline. Throughout stage 2 of STREAM, new drug choices and a rapidly changing treatment landscape have necessitated changes to the trial’s design to ensure it remains ethical and relevant. This paper describes changes to the trial design to ensure that stage 2 continues to answer important questions. These changes include the early closure to recruitment of two trial arms and an adjustment to the definition of the primary endpoint. If the STREAM experimental regimens are shown to be non-inferior or superior to the stage 1 study regimen, this would represent an important contribution to evidence about potentially more tolerable and more efficacious MDR-TB regimens, and a welcome advance for patients with rifampicin-resistant tuberculosis and tuberculosis control programmes globally.Trial registration: ISRCTN ISRCTN18148631. Registered 10 February 2016
Behavioural intervention to promote the uptake of planned care in urgent dental care attenders: study protocol for the RETURN randomised controlled trial
Authors: Harris R. , Lowers V. , Hulme C. , Burnside G. , Best A. , Clarkson J. E. , Cooke R. , Van Der Zande M. , Maitland R. 
Published: June 2022

AbstractBackgroundPeople with disadvantaged backgrounds are less likely to visit the dentist for planned care, even though they have disproportionately poorer oral health. They are correspondingly more likely to experience dental problems and use urgent dental care, general practices and Accident and Emergency departments, which not only makes meeting their needs expensive, but, since these services often rely on prescriptions rather than addressing the clinical cause, can contribute to antimicrobial resistance.MethodsThe RETURN intervention has been developed with substantial community co-production, to be delivered opportunistically in urgent dental care settings. This brief intervention is delivered by dental nurses and involves material relevant to the ‘in-group’ targeted. The material includes booklets relating to barriers to planned dental visiting with corresponding short video clips featuring local people and including a modelling element. Dental nurses are trained to have supportive and non-judgemental conversations, assisting patients to set personal goals and action plans, which are reinforced in a follow-up text within a few weeks. A randomised controlled trial will be undertaken in 3 types of sites: dental practices delivering urgent care (a) within working hours, (b) out of hours, and (c) in a Dental Hospital. The trial will recruit 1180 adult urgent dental care users over 12 months, who have not visited a dentist for a planned care appointment for 2 years or more and do not have a dentist who they visit for routine care. It aims to investigate the effectiveness and cost-effectiveness of the intervention and to explore whether the intervention has different effects across the socio-economic gradient. Participants will be followed up at 6, 12 and 18 months after randomisation. Co-primary outcomes are attendance at a dental practice for planned care within 12 months and self-reported oral health-related quality of life at 12 months.DiscussionThis is a pragmatic trial, evaluating the effectiveness of the intervention under the usual condition in which it might be applied. Since dental practices work as independent contractors to the NHS, this brings implementation and fidelity challenges which will be explored and described in embedded qualitative work.Trial registrationISRCTN registry identifier ISRCTN84666712. Registered 12/04/2021.