bluuebunny/crossref_metadata_2025 huggingface dataset:
Design, Calibration, and Control of Compliant Force-Sensing Gripping Pads for Humanoid Robots
Authors: Han Yuanfeng , Jiang Boren , Chirikjian Gregory S.
Published: April 2023

This paper introduces a pair of low-cost, light-weight, and compliant force-sensing gripping pads used for manipulating box-like objects with smaller-sized humanoid robots. These pads measure normal gripping forces and center of pressure (CoP). A calibration method is developed to improve the CoP measurement accuracy. A hybrid force-alignment-position control framework is proposed to regulate the gripping forces and to ensure the surface alignment between the grippers and the object. Limit surface theory is incorporated as a contact friction modeling approach to determine the magnitude of gripping forces for slippage avoidance. The integrated hardware and software system is demonstrated with an NAO humanoid robot. Experiments show the effectiveness of the overall approach.
APOE
ε4 associates with microglial activation independently of Aβ plaques and tau tangles
Authors: Ferrari-Souza João Pedro , Lussier Firoza Z. , Leffa Douglas T. , Therriault Joseph , Tissot Cécile , Bellaver Bruna , Ferreira Pâmela C. L. , Malpetti Maura , Wang Yi-Ting , Povala Guilherme , Benedet Andréa L. , Ashton Nicholas J. , Chamoun Mira , Servaes Stijn , Bezgin Gleb , Kang Min Su , Stevenson Jenna , Rahmouni Nesrine , Pallen Vanessa , Poltronetti Nina Margherita , O’Brien John T. , Rowe James B. , Cohen Ann D. , Lopez Oscar L. , Tudorascu Dana L. , Karikari Thomas K. , Klunk William E. , Villemagne Victor L. , Soucy Jean-Paul , Gauthier Serge , Souza Diogo O. , Zetterberg Henrik , Blennow Kaj , Zimmer Eduardo R. , Rosa-Neto Pedro , Pascoal Tharick A.
Published: April 2023

Animal studies suggest that the apolipoprotein E ε4 (
APOE
ε4) allele is a culprit of early microglial activation in Alzheimer’s disease (AD). Here, we tested the association between
APOE
ε4 status and microglial activation in living individuals across the aging and AD spectrum. We studied 118 individuals with positron emission tomography for amyloid-β (Aβ; [
18
F]AZD4694), tau ([
18
F]MK6240), and microglial activation ([
11
C]PBR28). We found that
APOE
ε4 carriers presented increased microglial activation relative to noncarriers in early Braak stage regions within the medial temporal cortex accounting for Aβ and tau deposition. Furthermore, microglial activation mediated the Aβ-independent effects of
APOE
ε4 on tau accumulation, which was further associated with neurodegeneration and clinical impairment. The physiological distribution of
APOE
mRNA expression predicted the patterns of
APOE
ε4-related microglial activation in our population, suggesting that
APOE
gene expression may regulate the local vulnerability to neuroinflammation. Our results support that the
APOE
ε4 genotype exerts Aβ-independent effects on AD pathogenesis by activating microglia in brain regions associated with early tau deposition.
The landscape of cryptic antisense transcription in human cancers reveals an oncogenic noncoding RNA in lung cancer
Authors: Zhao Zhaozhao , Chen Yu , Cheng Xiaomeng , Huang Leihuan , Wen Haimei , Xu Qiushi , Zhou Xiaolan , Zhang Xiaoyang , Chen Jing , Ni Ting
Published: April 2023

Cryptic transcription initiation has been previously linked to activation of oncogenic transcripts. However, the prevalence and impact of cryptic antisense transcription from the opposite strand of protein-coding genes were mostly unknown in cancer. Applying a robust computational pipeline to publicly available transcriptome and epigenome datasets, we identified hundreds of previously unannotated cryptic antisense polyadenylated transcripts (CAPTs) that were enriched in tumor samples. We showed that the activation of cryptic antisense transcription was associated with increased chromatin accessibility and active histone marks. Accordingly, we found that many of the antisense transcripts were inducible by treatment of epigenetic drugs. Moreover, CRISPR-mediated epigenetic editing assays revealed that transcription of a noncoding RNA
LRRK1
-CAPT promoted LUSC cell proliferation, suggesting its oncogenic role. Our findings largely expand our understanding of cancer-associated transcription events, which may facilitate the development of novel strategies for cancer diagnosis and treatment.
3D reconstruction of the cerebellar germinal layer reveals tunneling connections between developing granule cells
Authors: Cordero Cervantes Diégo , Khare Harshavardhan , Wilson Alyssa Michelle , Mendoza Nathaly Dongo , Coulon-Mahdi Orfane , Lichtman Jeff William , Zurzolo Chiara
Published: April 2023

The difficulty of retrieving high-resolution, in vivo evidence of the proliferative and migratory processes occurring in neural germinal zones has limited our understanding of neurodevelopmental mechanisms. Here, we used a connectomic approach using a high-resolution, serial-sectioning scanning electron microscopy volume to investigate the laminar cytoarchitecture of the transient external granular layer (EGL) of the developing cerebellum, where granule cells coordinate a series of mitotic and migratory events. By integrating image segmentation, three-dimensional reconstruction, and deep-learning approaches, we found and characterized anatomically complex intercellular connections bridging pairs of cerebellar granule cells throughout the EGL. Connected cells were either mitotic, migratory, or transitioning between these two cell stages, displaying a chronological continuum of proliferative and migratory events never previously observed in vivo at this resolution. This unprecedented ultrastructural characterization poses intriguing hypotheses about intercellular connectivity between developing progenitors and its possible role in the development of the central nervous system.
Diverse rescue potencies of p53 mutations to ATO are predetermined by intrinsic mutational properties
Authors: Song Huaxin , Wu Jiale , Tang Yigang , Dai Yuting , Xiang Xinrong , Li Ya , Wu Lili , Wu Jiaqi , Liang Ying , Xing Yangfei , Yan Ni , Li Yuntong , Wang Zhengyuan , Xiao Shujun , Li Jiabing , Zheng Derun , Chen Xinjie , Fang Hai , Ye Chenjing , Ma Yuting , Wu Yu , Wu Wen , Li Junming , Zhang Sujiang , Lu Min
Published: April 2023

Tumor suppressor p53 is inactivated by thousands of heterogeneous mutations in cancer, but their individual druggability remains largely elusive. Here, we evaluated 800 common p53 mutants for their rescue potencies by the representative generic rescue compound arsenic trioxide (ATO) in terms of transactivation activity, cell growth inhibition, and mouse tumor–suppressive activities. The rescue potencies were mainly determined by the solvent accessibility of the mutated residue, a key factor determining whether a mutation is a structural one, and the temperature sensitivity, the ability to reassemble the wild-type DNA binding surface at a low temperature, of the mutant protein. A total of 390 p53 mutants were rescued to varying degrees and thus were termed as type 1, type 2a, and type 2b mutations, depending on the degree to which they were rescued. The 33 type 1 mutations were rescued to amounts comparable to the wild type. In PDX mouse trials, ATO preferentially inhibited growth of tumors harboring type 1 and type 2a mutants. In an ATO clinical trial, we report the first-in-human mutant p53 reactivation in a patient harboring the type 1 V272M mutant. In 47 cell lines derived from 10 cancer types, ATO preferentially and effectively rescued type 1 and type 2a mutants, supporting the broad applicability of ATO in rescuing mutant p53. Our study provides the scientific and clinical communities with a resource of the druggabilities of numerous p53 mutations (
www.rescuep53.net
) and proposes a conceptual p53-targeting strategy based on individual mutant alleles rather than mutation type.
Salmonella Invasion Is Controlled by Competition among Intestinal Chemical Signals
Authors: Chowdhury Rimi , Pavinski Bitar Paulina D. , Chapman Hanora M. , Altier Craig
Published: April 2023

Enteric pathogens acutely sense their environment for signals to regulate their virulence functions. We demonstrate here that the enteric pathogen
Salmonella
utilizes the competition among certain regional intestinal constituents to modulate its virulence determinants in that region.
A Decrease in Fatty Acid Synthesis Rescues Cells with Limited Peptidoglycan Synthesis Capacity
Authors: Willdigg Jessica R. , Patel Yesha , Helmann John D.
Published: April 2023

Understanding how a bacterium coordinates cell envelope synthesis is essential to fully appreciate how bacteria grow, divide, and resist cell envelope stresses, such as β-lactam antibiotics. Balanced synthesis of the peptidoglycan cell wall and the cell membrane is critical for cells to maintain shape and turgor pressure and to resist external cell envelope threats.
Intragranuloma Accumulation and Inflammatory Differentiation of Neutrophils Underlie Mycobacterial ESX-1-Dependent Immunopathology
Authors: Lienard Julia , Munke Kristina , Wulff Line , Da Silva Clément , Vandamme Julien , Laschanzky Katie , Joeris Thorsten , Agace William , Carlsson Fredric
Published: April 2023

The ESX-1 type VII secretion system is required for virulence of pathogenic mycobacteria, including
Mycobacterium tuberculosis
. ESX-1 interacts with infected macrophages, but its potential roles in regulating other host cells and immunopathology have remained largely unexplored.
Draft Genome Sequence of Pseudomonas carnis Strain 23-145, Causing Blue Discolorations on Rabbit Carcasses
Authors: Biggel Michael , Lienhard Julia , Stephan Roger
Published: April 2023

Here, we report the genome sequence of
Pseudomonas carnis
strain 23-145, which was recovered from a rabbit carcass with blue discolorations. The strain harbored two
trpABCDF
loci involved in tryptophan biosynthesis, which is characteristic of blue-pigment-producing
Pseudomonas
strains.
Reconnaissance of Oxygenic Denitrifiers in Agriculturally Impacted Soils
Authors: Schmitz Emily V. , Just Craig L. , Schilling Keith , Streeter Matthew , Mattes Timothy E.
Published: April 2023

The direct investigation of
nod
genes in agricultural sites is limited, with no prior studies investigating
nod
genes at tile drains. An improved understanding of
nod
gene diversity and distribution is significant to the field of bioremediation and ecosystem services. The expansion of the
nod
gene database will advance oxygenic denitrification as a potential strategy for sustainable nitrate and nitrous oxide mitigation, specifically for agricultural sites.
Impacts of Nutrients on Alkene Biodegradation Rates and Microbial Community Composition in Enriched Consortia from Natural Inocula
Authors: Byrne Emily , Schum Simeon , Schaerer Laura , Techtmann Stephen M.
Published: April 2023

Excess plastic waste poses a major environmental problem. Microorganisms can metabolize many of the breakdown products (alkenes) of plastics.
Oil-Based Sanitization in Low-Moisture Environments: Delivery of Acetic Acid with Water-in-Oil Emulsions
Authors: Chuang Shihyu , Ghoshal Mrinalini , McLandsborough Lynne
Published: April 2023

Aqueous-based cleaning and sanitation are undesirable in processing facilities that manufacture low-moisture foods such as peanut butter and chocolate. Alcohol-based sanitization is advantageous because it leaves no residue on the contact surface but requires the processing facility to close temporarily due to flammability.
Tulsa 1000: a naturalistic study protocol for multilevel assessment and outcome prediction in a large psychiatric sample
Authors: Victor Teresa A , Khalsa Sahib S , Simmons W Kyle , Feinstein Justin S , Savitz Jonathan , Aupperle Robin L , Yeh Hung-Wen , Bodurka Jerzy , Paulus Martin P
Published: April 2023

Introduction

Although neuroscience has made tremendous progress towards understanding the basic neural circuitry underlying important processes such as attention, memory and emotion, little progress has been made in applying these insights to psychiatric populations to make clinically meaningful treatment predictions. The overall aim of the Tulsa 1000 (T-1000) study is to use the NIMH Research Domain Criteria framework in order to establish a robust and reliable dimensional set of variables that quantifies the positive and negative valence, cognition and arousal domains, including interoception, to generate clinically useful treatment predictions.

Methods and analysis

The T-1000 is a naturalistic study that will recruit, assess and longitudinally follow 1000 participants, including healthy controls and treatment-seeking individuals with mood, anxiety, substance use and eating disorders. Each participant will undergo interview, behavioural, biomarker and neuroimaging assessments over the course of 1 year. The study goal is to determine how disorders of affect, substance use and eating behaviour organise across different levels of analysis (molecules, genes, cells, neural circuits, physiology, behaviour and self-report) to predict symptom severity, treatment outcome and long-term prognosis. The data will be used to generate computational models based on Bayesian statistics. The final end point of this multilevel latent variable analysis will be standardised assessments that can be developed into clinical tools to help clinicians predict outcomes and select the best intervention for each individual, thereby reducing the burden of mental disorders, and taking psychiatry a step closer towards personalised medicine.

Ethics and dissemination

Ethical approval was obtained from Western Institutional Review Board screening protocol #20101611. The dissemination plan includes informing health professionals of results for clinical practice, submitting results to journals for peer-reviewed publication, presenting results at national and international conferences and making the dataset available to researchers and mental health professionals.

Trial registration number

NCT02450240; Pre-results.
Photomodulation in the treatment of chronic pain in patients with temporomandibular disorder: protocol for cost-effectiveness analysis
Authors: Sobral Ana Paula Taboada , Godoy Camila Leal H de , Fernandes Kristianne P Santos , Bussadori Sandra Kalil , Ferrari Raquel Agnelli Mesquita , Horliana Anna Carolina Ratto Tempestini , Monken Sonia F , Motta Lara J
Published: April 2023

Introduction

Epidemiological data show that the signs and symptoms of temporomandibular disorder (TMD) start becoming apparent from 6 years of age, and during adolescence these signs and symptoms are similar to those of adults. The present study aims to estimate the direct costs for treatment of chronic muscle pain with photobiomodulation therapy, occlusal splint and placebo in patients with TMD; to evaluate the effectiveness of photobiomodulation therapy and occlusal splint for treatment of muscle pain in patients with TMD; to analyse the cost-effectiveness of the two proposed treatments for pain; and to describe and compare the results of the analyses of these treatments.

Methods and analysis

This is a prospective trial of clinical and economic analyses that will include 135 patientswith TMD aged between 15 years and 25 years, randomly assigned to a treatment group: G1 (photobiomodulation), G2 (occlusal splint) and G3 (placebo). The analyses will be based on the cost of each treatment during the 12-month period. The outcome of the analysis of effectiveness will be pain, measured periodically by means of clinical examination of Research Diagnostic Criteria for Temporomandibular Disorders. The cost-effectiveness ratio will be calculated using, as end points, pain and the ratio of the differences in costs between the groups studied. The evaluation of the impact of the treatment on quality of life will be determined by applying the adapted EuroQol-5D.

Ethics and dissemination

This protocol has been ethically approved by the local medical ethical committee, protocol number 2.014.339. Results will be submitted to international peer-reviewed journals and presented at international conferences.

Trial registration number

NCT03096301.
Determinants of return at work of breast cancer patients: results from the OPTISOINS01 French prospective study
Authors: Arfi Alexandra , Baffert Sandrine , Soilly Anne-Laure , Huchon Cyrille , Reyal Fabien , Asselain Bernard , Neffati Souhir , Rouzier Roman , Héquet Delphine
Published: April 2023

Introduction

Return to work (RTW) after breast cancer (BC) is still a new field of research. The factors determining shorter sick leave duration of patients with BC have not been clearly identified. The aim of this study was to describe work during BC treatment and to identify factors associated with sick leave duration.

Materials and methods

An observational, prospective, multicentre study was conducted among women with operable BC. A logbook was given to all working patients to record sociodemographic and work-related data over a 1-year period.

Results

Work-related data after BC were available for 178 patients (60%). The median age at diagnosis was 50 years (27–77), 87.9% of patients had an invasive form of BC and 25.3% a lymph node involvement. 25.9% had a radical surgery and 24.2% had an axillary dissection. Radiotherapy was performed in 90.9% of patients and chemotherapy in 48.1%. Sick leave was prescribed for 165 patients (92.7%) for a median of 155 days. On univariate analysis, invasive BC (p=0.025), lymph node involvement (p=0.005), radical surgery (p=0.025), axillary dissection (p=0.004), chemotherapy (p<0.001), personal income <€1900/month (p=0.03) and not having received the patient information booklet on RTW (p=0.047) were found to be associated with a longer duration of sick leave. On multivariate analysis, chemotherapy was found to be associated with longer sick leave (OR: 3.5; 95% CI 1.6 to 7.9; p=0.002). The cost of sick leave to French National Health Insurance was fourfold higher in the case of chemotherapy (p<0.001).

Conclusion

Advanced disease and chemotherapy are major factors that influence sick leave duration during the management of BC.

Trial registration number

NCT02813317.
We12BFit!-Improving lifestyle physical activity in children aged 7-12 years with developmental coordination disorder: protocol of a multicentre single-arm mixed-method study
Authors: Braaksma Petra , Stuive Ilse , Boomsma Hinke , van der Sluis Corry K , Schoemaker Marina M , Dekker Rienk
Published: April 2023

Introduction

Children with developmental coordination disorder (DCD) are less physically active than their typically developing peers. No substantiated interventions are available to address this issue. Therefore, this study aims to describe the design and rationale of (1) a family-focused intervention to increase motivation for physical activity (PA) and, indirectly, lifestyle PA in children aged 7–12 years with DCD and (2) the methods to examine its preliminary effectiveness and feasibility.

Methods and analysis

This intervention is the second part of a more comprehensive, multidisciplinary treatment called We12BFit! The intervention was developed using the steps of treatment theory which includes the concept of targets, mechanism of action and essential ingredients. The content of the intervention is based on the transtheoretical model of change (TTM). In the intervention, the motivation for PA will be targeted through application of behaviour change strategies that fit the stages of the TTM. The modes of delivery include: pedometer, poster, parent meeting, booklet and coaching. At least 19 children with DCD, aged 7–12 years, will be included from two schools for special education and two rehabilitation centres. The intervention will be evaluated using a single-arm mixed-method design. Effectiveness will be assessed at three instances by using ActiGraph accelerometers accompanied by an activity log. Feasibility will be assessed using interviews with the participants and coaches. This evaluation may add to our understanding of motivation for PA in children with DCD and may eventually improve the rehabilitation programme of children with DCD.

Ethics and dissemination

The study has been approved by the Medical Ethics Committee of the University Medical Center of Groningen (METc 2015.216). We will disseminate the final results to the public through journal publications and presentations for practice providers and scientists. A final study report will also be provided to funding organisations.

Protocol version

4, 12 April 2018.

Trial registration number

NCT6334; Pre-results.
Randomised controlled feasibility trial of standard wound management versus negative-pressure wound therapy in the treatment of adult patients having surgical incisions for hip fractures
Authors: Masters James P M , Achten Juul , Cook Jonathan , Dritsaki Melina , Sansom Lucy , Costa Matthew L
Published: April 2023

Introduction

Deep wound infection is a catastrophic complication after hip fracture surgery. However, current understanding of infection rates in this population is limited. Many technologies such as incisional negative-pressure wound therapy (NPWT) show promise in reducing the rate of infection. This trial is a feasibility study looking to establish a value estimated with a greater precision of the rate of deep infection after hip fracture treatment in patients treated with NPWT versus standard dressing following hip fracture surgery.

Methods and analysis

A randomised controlled trial of 464 patients will be run across multiple centres. It is embedded in the World Hip Trauma Evaluation cohort study. Any patient over the age of 65 years having surgery for hip fracture is eligible unless they are being treated with percutaneous screw fixation. A web-based randomisation sequence will stratify patients by centre. Patients will be allocated to either NPWT or standard care on a 1:1 basis. The primary outcome measure is the Centre for Disease Control definition of deep infection at 30 days. Follow-up at 4 months will also assess deep infection and the core outcome dataset for hip fractures. This includes health-related quality of life (EQ-5D-5L), mobility, mortality and late complications such as further surgery. The primary analysis will be intention to treat.

Ethics and dissemination

Oxford C Research Ethics Committee granted ethical approval on 28/04/2017, 17/SC/0207. The results of this study will be reported in a peer-reviewed publication and inform the design of a future full-scale trial.

Trial registration number

NCT55305726
Reperfusion Injury after ischemic Stroke Study (RISKS): single-centre (Florence, Italy), prospective observational protocol study
Authors: Piccardi Benedetta , Arba Francesco , Nesi Mascia , Palumbo Vanessa , Nencini Patrizia , Giusti Betti , Sereni Alice , Gadda Davide , Moretti Marco , Fainardi Enrico , Mangiafico Salvatore , Pracucci Giovanni , Nannoni Stefania , Galmozzi Francesco , Fanelli Alessandra , Pezzati Paola , Vanni Simone , Grifoni Stefano , Sarti Cristina , Lamassa Maria , Poggesi Anna , Pescini Francesca , Pantoni Leonardo , Gori Anna Maria , Inzitari Domenico
Published: April 2023

Introduction

Treatments aiming at reperfusion of the acutely ischaemic brain tissue may result futile or even detrimental because of the so-called reperfusion injury. The processes contributing to reperfusion injury involve a number of factors, ranging from blood–brain barrier (BBB) disruption to circulating biomarkers. Our aim is to evaluate the relative effect of imaging and circulating biomarkers in relation to reperfusion injury.

Methods and analysis

Observational hospital-based study that will include 140 patients who had ischaemic stroke, treated with systemic thrombolysis, endovascular treatment or both. BBB disruption will be assessed with CT perfusion (CTP) before treatment, and levels of a large panel of biomarkers will be measured before intervention and after 24 hours. Relevant outcomes will include: (1) reperfusion injury, defined as radiologically relevant haemorrhagic transformation at 24 hours and (2) clinical status 3 months after the index stroke. We will investigate the separate and combined effect of pretreatment BBB disruption and circulating biomarkers on reperfusion injury and clinical status at 3 months. Study protocol is registered athttp://www.clinicaltrials.gov(ClinicalTrials.gov ID:NCT03041753).

Ethics and dissemination

The study protocol has been approved by ethics committee of the Azienda Ospedaliero Universitaria Careggi (Università degli Studi di Firenze). Informed consent is obtained by each patient at time of enrolment or deferred when the participant lacks the capacity to provide consent during the acute phase. Researchers interested in testing hypotheses with the data are encouraged to contact the corresponding author. Results from the study will be disseminated at national and international conferences and in medical thesis.

Trial registration number

NCT03041753.
Height-based dosing algorithm of bupivacaine in spinal anaesthesia for decreasing maternal hypotension in caesarean section without prophylactic fluid preloading and vasopressors: study protocol for a randomised controlled non-inferiority trial
Authors: Huang Bowan , Huang Qiang , Hai Chao , Zheng Zihao , Li Yali , Zhang Zhongjun
Published: April 2023

Introduction

Effectively preventing or treating spinal-induced maternal hypotension is considered to be the Holy Grail of obstetric anaesthesia. Prophylactic fluid preloading and vasopressors decrease hypotension but may aggravate heart load, induce fetal acidosis or maternal bradycardia. Using low-dose local anaesthetic decreases hypotension but may cause insufficient anaesthesia. Whether there is a height-based dosing algorithm of local anaesthetic in spinal anaesthesia for caesarean section that can provide sufficient anaesthesia with less hypotension without prophylactic fluid preloading and vasopressors is unclear. This study was designed to investigate a height-based dosing algorithm of bupivacaine in spinal anaesthesia for caesarean section.

Methods and analysis

This single-centre, double-blinded, prospective, non-inferiority, randomised controlled trial will include 264 parturients (between 18 and 45 years of age) who are scheduled for caesarean section. All participants will not receive prophylactic fluid preloading. The participants will be randomly divided into two groups: the test group or conventional group. For parturients in the test group, 0.5% isobaric bupivacaine (1.15–1.70 mL) will be injected into the subarachnoid space without prophylactic vasopressors. The bupivacaine dose depends on the height of subjects. For parturients in the conventional group, 0.5% bupivacaine (1.8 mL) will be injected into the subarachnoid space along with prophylactic vasopressors. The primary outcome is the incidence of maternal hypotension. The secondary outcomes include the failure rate of spinal anaesthesia, level of sensory block, degree of motor block, other complications in parturients, time of operation, neonatal outcome and quality of anaesthesia.

Ethics and dissemination

This study was approved by the Ethics Committee of Shenzhen People’s Hospital of Jinan University (Permit No. SZY-00251, chairperson Xiaofang Yu) on 8 February 2018The study results will be disseminated through peer-reviewed journals, professional societies and meetings.

Trial registration number

NCT03497364; Pre-results.
Effect of continuum-of-care intervention package on improving contacts and quality of maternal and newborn healthcare in Ghana: a cluster randomised controlled trial
Authors: Okawa Sumiyo , Gyapong Margaret , Leslie Hannah , Shibanuma Akira , Kikuchi Kimiyo , Yeji Francis , Tawiah Charlotte , Addei Sheila , Nanishi Keiko , Oduro Abraham Rexford , Owusu-Agyei Seth , Ansah Evelyn , Asare Gloria Quansah , Yasuoka Junko , Hodgson Abraham , Jimba Masamine
Published: April 2023

Objective

To evaluate the effect of a continuum-of-care intervention package on adequate contacts of women and newborn with healthcare providers and their reception of high-quality care.

Design

Cluster randomised controlled trial.

Setting

32 subdistricts in 3 rural sites in Ghana.

Participants

The baseline survey involved 1480 women who delivered before the trial, and the follow-up survey involved 1490 women who received maternal and newborn care during the trial.

Interventions

The intervention package included training healthcare providers, using an educational and recording tool named ‘continuum-of-care card’, providing the first postnatal care (PNC) by retaining women and newborns at healthcare facility or home visit by healthcare providers.

Outcome measures

Adequate contacts were defined as at least four contacts during pregnancy, delivery with assistance of skilled healthcare providers at a healthcare facility and three timely contacts within 6 weeks postpartum. High-quality care was defined as receiving 6 care items for antenatal care (ANC), 3 for peripartum care (PPC) and 14 for PNC.

Results

The difference-in-difference method was used to assess the effects of the intervention on the study outcome. The percentage of adequate contacts with high-quality care in the intervention group in the follow-up survey and the adjusted difference-in-difference estimators were 12.6% and 2.2 (p=0.61) at ANC, 31.5% and 1.9 (p=0.73) at PPC and 33.7% and 12.3 (p=0.13) at PNC in the intention-to-treat design, whereas 13.0% and 2.8 (p=0.54) at ANC, 34.2% and 2.7 (p=0.66) at PPC and 38.1% and 18.1 (p=0.02) at PNC in the per-protocol design that assigned the study sample by possession of the continuum-of-care card.

Conclusions

The interventions improved contacts with healthcare providers and quality of care during PNC. However, having adequate contact did not guarantee high-quality care. Maternal and newborn care in Ghana needs to improve its continuity and quality.

Trial registration number

NCT90618993.
Psychotropic medication and psychotherapeutic treatment of adults with intellectual disabilities (PROMPT-ID): a cross-sectional, epidemiological study in Saxony, Germany
Authors: Koch Andrea , Dobrindt Julia , Schützwohl Matthias
Published: April 2023

Introduction

The psychotropic medication and psychotherapeutic treatment of adults with intellectual disabilities study is a cross-sectional, epidemiological study carried out in Saxony, Germany. The main aim of the study is, among others, to assess the prevalence and quality of psychotropic medication in adults with ID.

Methods

Inclusion criteria are mild to profound forms of ID and an age of 18 years or older. A representative sample is realised by a two-stage sampling procedure. Study participants will be recruited from sheltered workshops (SW) and sheltered housings (SH). The stratified cluster sampling is realised by a random selection of service providing institutions followed by a random selection of adults with ID. An estimated total number of n=200 study participants via SW and n=400 via SH will be contacted to obtain data of approximately n=131 study participants recruited through SW and n=232 participants through SH. Thus, based on a psychotropic medication prevalence of 30%, an estimated number of n=109 in-depth interviews about psychotropic prescription practice will be carried out. Data collection is realised through interviews with key carers in the living environment. If psychotropics are prescribed currently, basic information (eg, dosage, treatment duration) are obtained, and a newly developed interview targeting the quality of the psychotropic medication treatment is conducted both with the carers and with the prescribing physicians. In addition to the prevalence and quality of psychotropic treatment, other parameters (eg, mental healthcare utilisation, psychiatric symptomatology, problem behaviour, institutional factors and parameters of the provision area) are assessed using well-established instruments.

Ethics and dissemination

Approval of the responsible ethics committee was obtained. Findings will be disseminated to participating institutions, published in journals and conferences and fill the lack of representative data that is urgently needed in this often criticised health service area. They shall help to improve mental health services in adults with ID prospectively.

Trial registration number

NCT03558815
The AID study: protocol for a randomised controlled trial of intrauterine insemination in the natural cycle compared with intracervical insemination in the natural cycle
Authors: Kop Petronella , van Wely Madelon , Nap Annemiek , Willem Mol Ben , Bernardus Rob , Brucker Michael De , Janssens Pim , Cohlen Ben , Pieters Jacqueline , Repping Sjoerd , van der Veen Fulco , Mochtar Monique H
Published: April 2023

Introduction

At present, studies comparing intrauterine insemination in the natural cycle versus intracervical insemination in the natural cycle in women undergoing artificial insemination with donor sperm are scarce.

Methods and analysis

We perform a randomised controlled non-inferiority trial among five secondary and tertiary fertility clinics in the Netherlands and one tertiary fertility clinic in Belgium. Women eligible for artificial insemination with donor sperm are included. We perform six cycles of artificial insemination with donor sperm within a time horizon of 8 months comparing intrauterine insemination in the natural cycle with intracervical insemination in the natural cycle. The primary outcome is ongoing pregnancy leading to live birth conceived within eight months after randomisation. Secondary outcomes are clinical pregnancy rate, miscarriage rate, multiple pregnancy rate, pregnancy complications (preterm birth, birth weight <2500 g, pregnancy induced hypertension, (pre-) eclampsia, Hemolysis Elevated Liver enzymes Low Platelets (HELLP)), time to ongoing pregnancy, direct and indirect costs. To demonstrate the non-inferiority of intracervical insemination with a margin of 12%, we need 208 women per arm.

Ethics and dissemination

The study has been approved by the Medical Ethical Committee of the Academic Medical Centre and from the Dutch Central Committee on research involving human subjects (47330-018-13). The boards of the participating hospitals approved the study. Results will be disseminated through peer-reviewed publications and presentations at international scientific meetings.

Trial registration number

NCT4462
Design of a randomised controlled trial of the effects of empagliflozin on myocardial perfusion, function and metabolism in type 2 diabetes patients at high cardiovascular risk (the SIMPLE trial)
Authors: Jürgens Mikkel , Schou Morten , Hasbak Philip , Kjær Andreas , Wolsk Emil , Zerahn Bo , Wiberg Mikkel , Brandt Niels Høgh , Gæde Peter Haulund , Rossing Peter , Faber Jens , Inzucchi Silvio , Gustafsson Finn , Kistorp Caroline Michaela
Published: April 2023

Introduction

A diagnosis of type 2 diabetes (T2D) more than doubles the risk of cardiovascular disease (CVD), with heart failure (HF) being one of the most common complications with a severe prognosis. The landmark Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Paitients (EMPA-REG OUTCOME) study demonstrated that treatment with the sodium glucose cotransporter-2 (SGLT-2) inhibitor empagliflozin rapidly and significantly reduces CVD mortality and admission rates for HF. However, the mechanisms behind this reduction in clinical events are unknown.

This study was designed to investigate the effects of the SGLT-2 inhibitor empagliflozin on myocardial perfusion and function in patients with T2D and high CVD risk.

Methods and analysis

In this investigator-initiated, randomised, double-blind controlled clinical trial, 92 patients with T2D and established CVD or high CVD risk will be randomised to treatment with empagliflozin 25 mg or a matching placebo for 13 weeks. The primary outcome measure is change in myocardial flow reserve measured quantitatively by Rubidium-82 position emission tomography. In a substudy, invasive haemodynamics at rest and during exercise will be measured at baseline and following the intervention, using right heart catheterisation.

Ethics and dissemination

The study protocol (v7, 02/08/2018) has been approved by the Ethics Committee of the Capital Region, Danish Data Protection Board and the Danish Medicines Agency, and it will be monitored according to the Good Clinical Practice regulations from the International Conference on Harmonization. The results be submitted to international peer-reviewed journals and be presented at conferences. The data will be made available to the public via EudraCT andwww.clinicaltrials.gov.

Trial registration number

NCT03151343.
Efficacy and safety of modified-release paracetamol for acute and chronic pain: a systematic review protocol
Authors: Margan Koletic Zeljana , Dosenovic Svjetlana , Puljak Livia
Published: April 2023

Introduction

Paracetamol (acetaminophen) is widely used for management of mild-to-moderate pain and reduction of fever. It is available as immediate release (IR) and modified-release (MR) formulation. In 2017, European Medicines Agency recommended a suspension of marketing of MR paracetamol in the European Union. Benefit-risk balance of these products has been assessed as negative as data showed that existing procedures for overdose management may not be efficient. Since MR paracetamol is still available in other countries (Australia and USA) and there is no available systematic review (SR) of efficacy and safety of MR paracetamol in the literature, we have decided to perform one to evaluate available data from randomised clinical trials (RCTs).

Methods and analysis

Using predefined search criteria, we will search EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov and WHO International Clinical Trials Registry Platform to identify RCTs evaluating efficacy and safety of MR paracetamol alone in any dose or duration for any pain. Participants are defined as adults and adolescents (over 12 years). Primary efficacy outcomes will be pain intensity, pain relief and sleep. Primary safety outcomes will be the number of patients experiencing any (serious) adverse event, the number of patients withdrawn due to adverse events and the number of patients with gastrointestinal and hepatic adverse events. Data analysis will be subdivided based on different clinical syndromes. Meta-analysis will be conducted if possible. Cochrane risk of bias (RoB) tool with seven dimensions will be used to assess RoB of individual studies.

Ethics and dissemination

This SR will include only data collected from trial reports; therefore, an ethical approval will not be sought. We will publish the protocol and our findings in peer-reviewed journals.

PROSPERO registration number

NCT42018115769.
Rehabilitation of cognitive deficits poststroke: protocol for a systematic review and meta-analysis of randomised controlled trials of non-pharmacological interventions
Authors: O Donoghue Mairead , Boland Pauline , Galvin Rose , Coote Susan , Hayes Sara
Published: April 2023

Introduction

Stroke is among the leading causes of death and disability worldwide. Poststroke cognitive impairment is a common sequela of stroke. The burden of cognitive impairment poststroke has significant impacts on the individual poststroke, their family and wider society. Despite the prevalence and associated burden of poststroke cognitive impairment, the optimal approach to rehabilitate cognitive deficits poststroke has yet to be established. A range of conservative interventions for cognitive impairment poststroke exist including self-efficacy training, physical activity interventions, neuropsychological interventions, electronic interventions, music therapy and occupational therapies. This systematic review aims to explore the totality of evidence with regard to non-pharmacological rehabilitation interventions wherein the primary or secondary aim is to improve cognitive function in individuals poststroke.

Methods and analysis

A systematic review of randomised controlled trials which investigate the effectiveness of interventions wherein the primary or secondary aim is to improve cognitive function in individuals poststroke will be conducted (August 2019). The following electronic databases will be searched: PubMed, Embase, CINAHL, CENTRAL and PsycInfo. Reference lists of all identified studies will be reviewed to identify additional studies for inclusion. Titles and abstracts will be screened independently by two review authors for inclusion and exclusion. Any disagreement regarding inclusion will be resolved by discussion or by referral to a third assessor if necessary. Methodological quality will be assessed using the Cochrane Risk of Bias Tool for Randomised Controlled Trials. Meta-analyses will be performed if studies are sufficiently homogeneous. The review will be reported in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement.

Ethics and dissemination

As this systematic review will collect secondary data only, ethical approval is not required. Findings will be disseminated through presentations and peer-reviewed journals.

Trial registration number

NCT42019125289.
Hybrid cardiac rehabilitation trial (HYCARET): protocol of a randomised, multicentre, non-inferiority trial in South America
Authors: Serón Pamela , Oliveros Maria J , Marzuca-Nassr Gabriel N , Lanas Fernando , Morales Gladys , Román Claudia , Muñoz Sergio R , Saavedra Nicolás , Grace Sherry L
Published: April 2023

Introduction

Cardiac rehabilitation (CR) programmes are well established, and their effectiveness and cost-effectiveness are proven. In spite of this, CR remains underused, especially in lower-resource settings such as Latin America. There is an urgent need to create more accessible CR delivery models to reach all patients in need. This trial aims to evaluate if the prevention of recurrent cardiovascular events is not inferior in a hybrid CR programme compared with a standard programme.

Method and analysis

A non-inferiority, pragmatic, multicentre, parallel (1:1), prospective, randomised and open with blinded endpoint assessment clinical trial will be conducted. 308 patients with coronary artery disease will be recruited consecutively. Participants will be randomised to hybrid or standard rehabilitation programme. The hybrid CR programme includes 10 supervised exercise sessions and individualised lifestyle counselling by a physiotherapist, with a transition after 4–6 weeks to unsupervised delivery via text messages and phone calls. The standard CR consists of 18–22 supervised exercise sessions, as well as group education sessions about lifestyle. Intervention in both groups is between 8 and 12 weeks. The primary outcome is a composite of cardiovascular mortality and hospitalisations due to cardiovascular causes. Secondary outcomes are health-related quality of life, exercise capacity, muscle strength, heart-healthy behaviour, return-to-work, cardiovascular risk factor, adherence, and exercise-related adverse events. The outcomes will be measured at the end of intervention, at 6 months and at 12 months follow-up from recruitment. The primary outcome will be tracked through the end of the trial. Per-protocol and intention-to-treat analysis will be undertaken.Cox regression model will be used to compare primary outcome among study groups.

Ethics and dissemination

Ethics committees at the sponsor institution and each centre where participants will be recruited approved the study protocol and the Informed Consent. Research findings will be published in peer-reviewed journals; additionally, results will be disseminated among region stakeholders.

Trial registration number

NCT03881150.

Date and version

01 October 2019.
ALADDIN study: does assisted hatching of vitrified/warmed blastocysts improve live birth rate? Protocol for a multicentric randomised controlled trial
Authors: Alteri Alessandra , Guarneri Cristina , Corti Laura , Restelli Liliana , Reschini Marco , Giardina Paolo , Papaleo Enrico , Somigliana Edgardo , Viganò Paola , Paffoni Alessio
Published: April 2023

Introduction

Recent data suggest a higher clinical pregnancy rate performing assisted hatching (AH) on previously cryopreserved embryos but fail to demonstrate significant effects on live birth rate. However, current evidence is based on studies with a small sample size and may hide a type II error. Moreover, poor attention has been given to the specific effect of AH on frozen/thawed blastocysts. To shed light on this topic, we developed the present protocol for a randomised trial to investigate the benefits of the laser-mediated partial removal of the zona pellucida in vitrified/warmed blastocysts.

Methods and analysis

The pArtiaL zonA pelluciDa removal by assisteD hatchINg of blastocysts (ALADDIN) study is a multicentric prospective comparative study with a parallel randomised controlled design aiming to investigate whether AH performed on warmed blastocysts before embryo transfer can improve live birth rate. Women allocated to the control group will undergo embryo transfer of blastocysts not previously subjected to AH. Two infertility units will be involved in the study. Enrolment of patients will last 18 months with quarterly monitoring and the entire study is foreseen to be closed in 36 months. Secondary outcomes include: proportion of transferred blastocysts/thawed blastocyst, morphological features of blastocysts before embryo transfer, implantation, biochemical pregnancy, clinical pregnancy (ultrasound visible gestational sac), miscarriage, multiple pregnancy, preterm birth (<37 weeks of gestation), obstetrical and neonatal complications and congenital anomaly rates.

Ethics and dissemination

This protocol received a favourable ethical opinion from the Ethical Committee of IRCCS San Raffaele Scientific Institute and the Ethical Committee Area 2 Milan. Each participant will provide written consent to participate and remain encoded during the study. The trial results will be published in peer-reviewed journals and presented at conferences.

Trial registration number

NCT03623659.