bluuebunny/crossref_metadata_2025 huggingface dataset:
59: EVIDENCE BASED DECISION MAKING ABOUT FACTORS AFFECTING CONSULTATION LENGTH OF PHYSICIANS WORLDWIDE: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: HajEbrahimi Sakineh , Janati Ali , Hasanpoor Edris , Arab-Zozani Morteza , Sokhanvar Mobin , Pashzadeh Fariba , HaghGoshyie Elaheh
Published: May 2024

Background and aims:

Consultation length is a crucial aspect of patient-physician interaction that its inadequacy can negatively influence the treatment and diagnosis efficiency. The purpose was to determine factors related to consultation length of physicians and we sought to compare consultation length in different countries worldwide.

Methods:

We searched PubMed, Web of Science, Cochrane, ProQuest, and Scopus. Also, we searched Google Scholar for finding of the entire articles that theses related to consultation length. We used data sources up to November, 2015, without language restriction and searched the reference lists of retrieved articles. We extracted Consultation length and Factors related to it and assessments for their methodological quality using the AXIS (Appraisal tool for Cross-Sectional Studies) checklist. Meta-analyses were conducted using Comprehensive Meta-Analysis Version (CMA) 2.0. We used a random-effects model for the meta-analyses of factors.

Results:

Of the 16 911 identified studies, 189 met full inclusion criteria. Of 189 studies assessed, 125 cases (67%) were conducted in USA, UK, Australia and Netherlands. Only, 49 (26%) studies were strong evidence. 164 (86.77%) studies were face to face consultations. The effect of three variables physicians' gender, patients' gender and type of consultation investigated on the consultation length. According to moderate and strong evidence, no statistically significant difference was found in the consultation length in female and male doctors (p=0.891). Also, no statistically significant difference was found in the consultation length between female and male patients (p=0.314) and telemedicine and face to face (p=0.170) visits.

Conclusions:

According to all evidence, The results showed that no association was identified between consultation length and three factors in the random-effects model. It seems patient-physician interaction more than studied variables, influence the length of consultations.
65: EXPLORING FACTORS INFLUENCING OVER-MEDICALIZATION: A SCOPING REVIEW
Authors: Doshmangir Parinaz , Doshmangir Leila , Shaghaghi Reza
Published: May 2024

Background and aims:

Medicalization is the process of extending medical gaze on human conditions which is not intrinsically bad phenomenon. Engaging in the medicalization out of defined thresholds or the bad form of medicalization is called over-medicalization. Detriment, dispensable death and waste of numerous resources are the causes of over-medicalization. The aim of this scoping review was to explore influential factors on over medicalization in the world.

Methods:

We did search in PubMed, Scopus, Cochrane, Ovid, Proquest as reliable databases. Articles that were investigated determinants of over medicalization in different themes were selected. All data entered in data extractions table and Meta synthesis method was used for qualitative research. Factors were grouped according to the musicalized subjects and categorized into three levels (personal, professional and social).

Results:

Out of 5118 articles identified for the study, over 70 factors were extracted from 30 articles addressing factors affecting over medicalization in various subjects. Among the extracted factors, the social and professional factors were respectively more than personal factors.

Conclusion:

Over-medicalization originates from a wide range of factors. Identifying potential influential factors in provision of unnecessary care is pivotal to eliminate the menace of this phenomenon. Extra social, political and cultural resources will be needed if the reported factors are to be tackled.
70: HEALTH INSURANCE AND THE UTILIZATION OF HEALTH CARE: A SYSTEMATIC REVIEW
Authors: Nosratnejad Shirin , Shami Elham
Published: May 2024

Background and aims:

All the countries are moving towards universal coverage insurance. in their ability to achieve universal coverage, it is likely that they would have similar effects on the health care utilization of the people who gained coverage. This study aimed to examine the relationship between health insurance status and utilization of health services.

Methods:

We conducted a systematic review using five electronic databases (PubMed, Scopus, and Web of science, ProQuest Medical Library, and Science Direct). We did the search up to April 2015. Two authors appraised the identified studies and then examined Factors associated with the coverage and utilization of health insurance of the study. We used two synthesis approaches: narrative synthesis and vote- counting.

Results:

According to inclusion criteria, 19 studies were included in the study. All retrieved articles were qualitative study. age, Gender, Education, Marriage, Employment, Health status, insurance status, household size, Income, Inpatient and Outpatient services, Physician visit, and Emergency visit are important factors on the utilization and influence the utilization of health services positively. Also health services utilization among insured was significantly higher than that of the uninsured households.

Conclusion:

health insurance increased access to health care and utilization of health services. Health insurance can also be induced demand too. But increasing utilization through health insurance doesn't improve health outcomes.
85: KNOWLEDGE, ATTITUDE AND PRACTICE OF HIV/AIDS: A SYSTEMATIC REVIEW AMONG KEY POPULATIONS AT RISK FOR HIV INFECTION IN IRAN
Authors: Hooshyar Samira Hosseini , Shahesmaeili Armita , Faramani Roya Safari , Khajehkazemi Razieh , Nasirian Maryam , Sharifi Hamid , Kamali Kianoosh
Published: May 2024

Background and aims:

According to the Ministry of Health and Medical education in Iran, 27000 cases of HIV/AIDS have been registered so far. Given the importance of key groups in the spread of HIV/AIDS alongside the significant role of prevention as the most important approach to tackle this infection, this study was designed to document the current state of the knowledge, attitude and practices of key populations towards HIV/AIDS in Iran.

Methods:

In this study, we systematically reviewed the scientific literature up to July 2014 on HIV/AIDS knowledge, attitude and practices. We focused on four key populations including female sex workers, prisoners, and injecting and non-injecting drug users. We searched PubMed, Scopus, Google Scholar, SID and Iranmedex databases. The search strategy was constructed using “and” and “or” operators and the following keywords: Female Sex Worker, Injecting Drug User, HIV, Prisoners, Drug User, Knowledge, Attitude, Practice and Iran. A checklist was designed to assess the internal validity and overall quality of each paper. Two independent reviewers assessed the quality of each paper. In case of disagreement, a third expert-opinion was sought.

Results:

A total of 195 studies were retrieved, of which 25 were repetitive and only 8 studies were included in the final review based on their good quality. Due to the diversity of research methodologies and applied tools in existing studies, performing a meta-analysis was not considered feasible. Among included studies, none had evaluated the HIV/AIDS related practice. Mean knowledge score was ranged from 40.29 to 50.6 and the mean attitude score was from 38.3 to 67.5. Moreover, the percentage of those with high level of knowledge varied between 6 and 44.5 and those with a high positive attitude between 7.6 and 38.1.

Conclusion:

Despite the importance of preventive behaviors among key groups in breaking the chain of HIV transmission, the lack of evidence in this area is clear. The need to design a comprehensive tool to assess the knowledge, attitude and practice of all subgroups, especially key populations at risk for HIV is a top priority of research in this area.
Randomised controlled trial of the clinical and cost-effectiveness of a peer-delivered self-management intervention to prevent relapse in crisis resolution team users: study protocol
Authors: Johnson Sonia , Mason Oliver , Osborn David , Milton Alyssa , Henderson Claire , Marston Louise , Ambler Gareth , Hunter Rachael , Pilling Stephen , Morant Nicola , Gray Richard , Weaver Tim , Nolan Fiona , Lloyd-Evans Brynmor
Published: May 2024

Introduction

Crisis resolution teams (CRTs) provide assessment and intensive home treatment in a crisis, aiming to offer an alternative for people who would otherwise require a psychiatric inpatient admission. They are available in most areas in England. Despite some evidence for their clinical and cost-effectiveness, recurrent concerns are expressed regarding discontinuity with other services and lack of focus on preventing future relapse and readmission to acute care. Currently evidence on how to prevent readmissions to acute care is limited. Self-management interventions, involving supporting service users in recognising and managing signs of their own illness and in actively planning their recovery, have some supporting evidence, but have not been tested as a means of preventing readmission to acute care in people leaving community crisis care. We thus proposed the current study to test the effectiveness of such an intervention. We selected peer support workers as the preferred staff to deliver such an intervention, as they are well-placed to model and encourage active and autonomous recovery from mental health problems.

Methods and analysis

The CORE (CRT Optimisation and Relapse Prevention) self-management trial compares the effectiveness of a peer-provided self-management intervention for people leaving CRT care, with treatment as usual supplemented by a booklet on self-management. The planned sample is 440 participants, including 40 participants in an internal pilot. The primary outcome measure is whether participants are readmitted to acute care over 1 year of follow-up following entry to the trial. Secondary outcomes include self-rated recovery at 4 and at 18 months following trial entry, measured using the Questionnaire on the Process of Recovery. Analysis will follow an intention to treatment principle. Random effects logistic regression modelling with adjustment for clustering by peer support worker will be used to test the primary hypothesis.

Ethics and dissemination

The CORE self-management trial was approved by the London Camden and Islington Research Ethics Committee (REC ref: 12/LO/0988). A Trial Steering Committee and Data Monitoring Committee oversee the progress of the study. We will report on the results of the clinical trial, as well as on the characteristics of the participants and their associations with relapse.

Trial registration number

ISRCTN01027104; pre-results stage.
Return-to-work intervention versus usual care for sick-listed employees: health-economic investment appraisal alongside a cluster randomised trial
Authors: Lokman Suzanne , Volker Danielle , Zijlstra-Vlasveld Moniek C , Brouwers Evelien PM , Boon Brigitte , Beekman Aartjan TF , Smit Filip , Van der Feltz-Cornelis Christina M
Published: May 2024

Objective

To evaluate the health-economic costs and benefits of a guided eHealth intervention (E-health module embedded in Collaborative Occupational healthcare (ECO)) encouraging sick-listed employees to a faster return to work.

Design

A two-armed cluster randomised trial with occupational physicians (OPs) (n=62), clustered and randomised by region into an experimental and a control group, to conduct a health-economic investment appraisal. Online self-reported data were collected from employees at baseline, after 3, 6, 9 and 12 months.

Setting

Occupational health care in the Netherlands.

Participants

Employees from small-sized and medium-sized companies (≥18 years), sick-listed between 4 and 26 weeks with (symptoms of) common mental disorders visiting their OP.

Interventions

In the intervention group, employees (N=131) received an eHealth module aimed at changing cognitions regarding return to work, while OPs were supported by a decision aid for treatment and referral options. Employees in the control condition (N=89) received usual sickness guidance.

Outcomes Measures

Net benefits and return on investment based on absenteeism, presenteeism, health care use and quality-adjusted life years (QALYs) gained.

Results

From the employer’s perspective, the incremental net benefits were €3187 per employee over a single year, representing a return of investment of €11 per invested Euro, with a break-even point at 6 months. The economic case was also favourable from the employee’s perspective, partly because of QALY health gains. The intervention was costing €234 per employee from a health service financier’s perspective. The incremental net benefits from a social perspective were €4210. This amount dropped to €3559 in the sensitivity analysis trimming the 5% highest costs.

Conclusions

The data suggest that the ECO intervention offers good value for money for virtually all stakeholders involved, because initial investments were more than recouped within a single year. The sometimes wide 95% CIs suggest that the costs and benefits are not always very precise estimates and real benefits could vary considerably.

Trial Registration

NTR2108; Results.
Qualitative interview study of antibiotics and self-management strategies for respiratory infections in primary care
Authors: McDermott Lisa , Leydon Geraldine M , Halls Amy , Kelly Jo , Nagle Amanda , White Jennifer , Little Paul
Published: May 2024

Objective

To explore perceptions of illness, the decisions to consult and the acceptability of delayed antibiotic prescriptions and self-help treatments for respiratory tract infections (RTIs).

Design

Qualitative semistructured interview study.

Setting

UK primary care.

Participants

20 adult patients who had been participating in the ‘PIPS’ (Pragmatic Ibuprofen Paracetamol and Steam) trial in the South of England.

Method

Semistructured telephone interviews were conducted with participants to explore their experiences and views on various treatments for RTI.

Results

Participants had concerns about symptoms that were not clinically serious and were mostly unaware of the natural history of RTIs, but were aware of the limitations of antibiotics and did not expect them with every consultation. Most viewed delayed prescriptions positively and had no strong preference over which technique is used to deliver the delayed antibiotic, but some patients received mixed messages, such as being told their infection was viral then being given an antibiotic, or were sceptical about the rationale. Participants disliked self-help treatments that involved taking medication and were particularly concerned about painkillers in combination. Steam inhalation was viewed as only moderately helpful for mild symptoms.

Conclusion

Delayed prescribing is acceptable no matter how the delay is operationalised, but explanation of the rationale is needed and care taken to minimise mixed messages about the severity of illnesses and causation by viruses or bacteria. Better access is needed to good natural history information, and the signs and symptoms requiring or not requiring general practitioner advice. Significant concerns about paracetamol, ibuprofen and steam inhalation are likely to need careful exploration in the consultation.
Pharmacy Diabetes Screening Trial: protocol for a pragmatic cluster-randomised controlled trial to compare three screening methods for undiagnosed type 2 diabetes in Australian community pharmacy
Authors: Krass Ines , Carter Rob , Mitchell Bernadette , Mohebbi Mohammadreza , Shih Sophy T F , Trinder Peta , Versace Vincent L , Wilson Frances , Namara Kevin Mc
Published: May 2024

Introduction

With the rising prevalence of type 2 diabetes in Australia, screening and earlier diagnosis is needed to provide opportunities to intervene with evidence-based lifestyle and treatment options to reduce the individual, social and economic impact of the disease. The objectives of the Pharmacy Diabetes Screening Trial are to compare the clinical effectiveness and cost-effectiveness of three screening models for type 2 diabetes in a previously undiagnosed population.

Methods and analysis

The Pharmacy Diabetes Screening Trial is a pragmatic cluster randomised controlled trial to be conducted in 363 community pharmacies across metropolitan, regional and remote areas of Australia, randomly allocated by geographical clusters to one of three groups, each with 121 pharmacies and 10 304 screening participants. The three groups are: group A: risk assessment using a validated tool (AUSDRISK); group B: AUSDRISK assessment followed by point-of-care glycated haemoglobin testing; and group C: AUSDRISK assessment followed by point-of-care blood glucose testing. The primary clinical outcome measure is the proportion of newly diagnosed cases of type 2 diabetes. Primary outcome comparisons will be conducted using the Cochran-Mantel-Haenszel test to account for clustering. The secondary clinical outcomes measures are the proportion of those who (1) are referred to the general practitioner (GP), (2) take up referral to the GP, (3) are diagnosed with pre-diabetes, that is, impaired glucose tolerance or impaired fasting glucose and (4) are newly diagnosed with either diabetes or pre-diabetes. The economic outcome measure is the average cost (direct and indirect) per confirmed new case of diagnosed type 2 diabetes based on the incremental net trial-based costs of service delivery and the associated incremental longer term health benefits from a health funder perspective.

Ethics and dissemination

The protocol has been approved by the Human Research Ethics Committees at University of Sydney and Deakin University. Results will be available on the Sixth Community Pharmacy Agreement website and will be published in peer reviewed journals.

Trial registration number

ACTRN12616001240437; Pre-results.
Factors influencing smartwatch use and comfort with health data sharing: a sequential mixed-method study protocol
Authors: Goodings Anthony James , Fadahunsi Kayode Philip , Tarn Derjung Mimi , Henn Patrick , Shiely Frances , O'Donoghue John
Published: May 2024

Introduction

Smartwatches have become ubiquitous for tracking health metrics. These data sets hold substantial potential for enhancing healthcare and public health initiatives; it may be used to track chronic health conditions, detect previously undiagnosed health conditions and better understand public health trends. By first understanding the factors influencing one’s continuous use of the device, it will be advantageous to assess factors that may influence a person’s willingness to share their individual data sets. This study seeks to comprehensively understand the factors influencing the continued use of these devices and people’s willingness to share the health data they generate.

Methods and analysis

A two-section online survey of smartwatch users over the age of 18 will be conducted (n ≥200). The first section, based on the expectation-confirmation model, will assess factors influencing continued use of smartwatches while the second section will assess willingness to share the health data generated from these devices. Survey data will be analysed descriptively and based on structural equation modelling.

Subsequently, six focus groups will be conducted to further understand the issues raised in the survey. Each focus group (n=6) will consist of three smartwatch users: a general practitioner, a public health specialist and an IT specialist. Young smartwatch users (aged 18–44) will be included in three of the focus groups and middle-aged smartwatch users (aged 45–64) will be included in the other three groups. This is to enhance comparison of opinions based on age groups. Data from the focus groups will be analysed using the microinterlocutor approach and an executive summary.

After the focus group, participants will complete a brief survey to indicate any changes in their opinions resulting from the discussion.

Ethics and dissemination

The results of this study will be disseminated through publication in a peer-reviewed journal, and all associated data will be deposited in a relevant, publicly accessible data repository to ensure transparency and facilitate future research endeavours.

This study was approved by the Social Research Ethic Committee (SREC), University College Cork—SREC/SOM/21062023/2.
Personalised functional imaging-guided multitarget continuous theta burst stimulation for post-stroke aphasia: study protocol for a randomised controlled trial
Authors: Huang Jianting , Ren Jianxun , Xie Wuxiang , Pan Ruiqi , Xu Na , Liu Hesheng
Published: May 2024

Introduction

Continuous theta burst stimulation (cTBS), a form of repetitive transcranial magnetic stimulation (rTMS), targeting the language network in the right hemisphere of post-stroke aphasia (PSA) patients shows promising results in clinical trials. However, existing PSA studies have focused on single-target rTMS, leaving unexplored the potential benefits of multitarget brain stimulation. Consequently, there is a need for a randomised clinical trial aimed to evaluate the efficacy and safety of cTBS targeting on multiple critical nodes in the language network for PSA.

Methods and analysis

This is a prospective, multicentre, double-blind, two-arm parallel-group, sham-controlled randomised trial. The study will include a total of 60 participants who will be randomly assigned in a 1:1 ratio to either the active cTBS group or the sham cTBS group. Using precision resting-state functional MRI for each participant, we will map personalised language networks and design personalised targets in the inferior frontal gyrus, superior temporal gyrus and superior frontal gyrus. Participants will undergo a 3-week cTBS intervention targeting the three personalised targets, coupled with speech and language therapy. The primary outcome is the change in the Western Aphasia Battery-Revised aphasia quotient score among participants after a 3-week treatment. Secondary outcomes include Boston Diagnostic Aphasia Examination severity ratings, Token Test and the Chinese-version of the Stroke and Aphasia Quality of Life Scale 39-generic version.

Ethics and dissemination

The study has been approved by the ethics committees of Affiliated Hospital of Hebei University, Hebei General Hospital and Affiliated Hospital of Chengde Medical University. The findings of this study will be reported in peer-reviewed scientific journals.

Trial registration number

The study has been registered on ClinicalTrials.gov (NCT05957445).
11 Caring for patients in a faith based setting: demonstrating a model for ‘hard to reach’ communities and achieving preferred place of death
Authors: Craig Rachel , Tookman Adrian , Gishen Faye
Published: May 2024

Introduction

A Marie Curie review1highlighted that the Jewish population, alongside Black and Minority Ethnic (BME) groups, are under-represented in utilising palliative care.2Explanations may include concerns around gaining trust and being culturally understood. Preferred Place of Death (PPoD) has been used as a key performance indicator (KPI) for measuring effective palliative care.

Aim

To establish a palliative care outreach clinic in a faith-based setting and subsequently evaluate patient experience and measure the KPI of PPoD.

Methods

In 2011 a cancer charity supporting the Jewish community, in collaboration with Marie Curie and The Royal Free London NHS Foundation Trust, developed a palliative care clinic, serving an area with a large Jewish population. The clinic runs weekly. A palliative care consultant sees and discusses all patients at the Marie Curie multidisciplinary team meeting. Data was collected via anonymous semi-structured patient experience survey in 2013 and 2016 and all patients are offered Advance Care Planning, including PPoD. Actual place of death has been recorded for all deceased patients.

Results

39 patients completed the survey. 100% rated the service ‘excellent’ or ‘good’

In 2016, 17 patients in the service died. 13 achieved their PPoD (76%).

Conclusion

Achieving a 76% PPoD contrasts with the London average of 38.1% deaths in usual place of residence.3This demonstrates the success of a faith based service catering for a traditionally ‘hard to reach’ population and represents a unique model within the United Kingdom. This model could be extended to other faith based communities to broaden access to palliative care.

References

1. https://www.mariecurie.org.uk/globalassets/media/documents/policy/policy-publications/june-2013/palliative-and-end-of-life-care-for-black-asian-and-minority-ethnic-groups-in-the-uk.pdf

2. Dorff E. End of Life; Jewish Perspectives.The Lancet2005;366:862–5

3. https://www.endoflifecare.org.uk/data_sources/place_of_death
24 The nordoff robbins music therapy service at marie curie hospice
Authors: Jezard Joseph
Published: May 2024

Introduction

The music therapy provision at Marie Curie Hospice Hampstead was established in September 2016. The service is provided by Nordoff-Robbins, the largest independent music therapy charity in the UK. The therapeutic approach is based on Nordoff-Robbins music therapy theory,1Community Music Therapy theory2and Resource Orientated music therapy theory.3The findings presented here are taken from a service evaluation report undertaken in March 2017.

Aim(s)

To inform music therapists and other health care professionals how a successful music therapy provision can be implemented and of the perceived impact a music therapy service can have within a hospice or similar setting.based on findings from a service evaluation report.

Marie Curie aims to ‘help people and their families with terminal illness make the most of the time they have together by delivering expert care, emotional support, research and guidance.‘ (1) This study will present if Nordoff Robbins music therapy fulfils the aim.

Method(s)

Questionnaires were distributed to service-users, family members, carers, friends, staff and the music therapist. Where appropriate participants were also asked to leave comments.

Results

The findings show that music therapy was seen to have a positive impact in four key themes: 100% of the respondents reported that music therapy had a positive impact on the skills and working environment within the Marie Curie Hospice, 96% of respondents reported that music therapy enabled people to engage in music, 93% of respondents reported a positive impact on interaction, communication and relationships and 90% of respondents reporting a positive impact of quality of life and well being.

Conclusion(s)

Marie Curie aims to ‘help people and their families with terminal illness make the most of the time they have together by delivering expert care, emotional support, research and guidance.4The results from the service evaluation indicate that the music therapy provision successfully contributes to the attainment of these aims and is a valued intervention.

References

. Nordoff P, Robbins C. Creative Music Therapy: A Guide to Fostering Clinical Musicianship (2nd Edition) 2007. Gilsum, NH: Barcelona Publishers.

. Pavlicevic M, Ansdell G, (Eds). Community Music Therapy 2004. London: Jessica Kingsley

. Rolvsjord R. Resource-Oriented Music Therapy in Mental Health Care 2010. Gilsum, NH: Barcelona Publishers.

. Marie Curie2017. Vision and Strategic Plan, UK, viewed 13 June 2017 https://www.mariecurie.org.uk/who/plans-reports-policies/vision-strategic-plan.
31 ’I’m fine’: exploring patient and carer assertions of status in advanced COPD and clinical implications
Authors: Moore Caroline , Gardener Anita Carole , Farquhar Morag , Ewing Gail , Duschinsky Robbie
Published: May 2024

Introduction

Patients can be reluctant to say that they need help and support, telling clinicians they are ‘’fine’’ despite having unmet needs. Research with patients in mental health settings suggests that when patients do this they are less likely to follow their treatment plans, and that their informal carers may be at a risk of depression. To date these findings have not been explored in patients with advancing physical health conditions or their carers.

Aim

To explore the presence and role of “I’m Fine” or equivalent assertions for patients with advanced COPD and their carers; and to examine the impact denials of support needs may have on their health and service-use.

Methods

Criteria based on Attachment Theory was used to identify ‘I’m Fine’ cases from the Living with Breathlessness Study (LWB) dataset of 235 patient and 115 carer qualitative interview transcripts. Data will be further analysed to explore discourses within cases using a Framework approach.

Results

Patients and carers who asserted they were ‘fine’ and not in need of further clinical support despite unmet needs had a distinct profile. Patients’ self-management attitudes and beliefs included minimising the effects and symptoms towards COPD, avoidance of thinking about the future and using stoical language in an attempt to downplay experiences. Carers focused on the needs of the patient whilst downplaying their own problems or distress.

Conclusion

Better understanding of the processes and implications of assertions of status will support future work on interventions to support patients and carers.
Safety and biological outcomes following a phase 1 trial of GD2-specific CAR-T cells in patients with GD2-positive metastatic melanoma and other solid cancers
Authors: Gargett Tessa , Truong Nga T H , Gardam Bryan , Yu Wenbo , Ebert Lisa M , Johnson Amy , Yeo Erica C F , Wittwer Nicole L , Tapia Rico Gonzalo , Logan Jesikah , Sivaloganathan Purany , Collis Maria , Ruszkiewicz Andrew , Brown Michael P
Published: May 2024

Background

Chimeric antigen receptor (CAR) T cell therapies specific for the CD19 and B-cell maturation antigen have become an approved standard of care worldwide for relapsed and refractory B-cell malignancies. If CAR-T cell therapy for non-hematological malignancies is to achieve the same stage of clinical development, then iterative early-phase clinical testing can add value to the clinical development process for evaluating CAR-T cell products containing different CAR designs and manufactured under differing conditions.

Methods

We conducted a phase 1 trial of third-generation GD2-specific CAR-T cell therapy, which has previously been tested in neuroblastoma patients. In this study, the GD2-CAR-T therapy was evaluated for the first time in metastatic melanoma patients in combination with BRAF/MEK inhibitor therapy, and as a monotherapy in patients with colorectal cancer and a patient with fibromyxoid sarcoma. Feasibility and safety were determined and persistence studies, multiplex cytokine arrays on sera and detailed immune phenotyping of the original CAR-T products, the circulating CAR-T cells, and, in select patients, the tumor-infiltrating CAR-T cells were performed.

Results

We demonstrate the feasibility of manufacturing CAR-T products at point of care for patients with solid cancer and show that a single intravenous infusion was well tolerated with no dose-limiting toxicities or severe adverse events. In addition, we note significant improvements in CAR-T cell immune phenotype, and expansion when a modified manufacturing procedure was adopted for the latter 6 patients recruited to this 12-patient trial. We also show evidence of CAR-T cell-mediated immune activity and in some patients expanded subsets of circulating myeloid cells after CAR-T cell therapy.

Conclusions

This is the first report of third-generation GD2-targeting CAR-T cells in patients with metastatic melanoma and other solid cancers such as colorectal cancer, showing feasibility, safety and immune activity, but limited clinical effect.

Trial registration number

ACTRN12613000198729.
Cognitive rehabilitation effects on grey matter volume and Go-NoGo activity in progressive multiple sclerosis: results from the CogEx trial
Authors: Rocca Maria A , Valsasina Paola , Romanò Francesco , Tedone Nicolò , Amato Maria Pia , Brichetto Giampaolo , Boccia Vincenzo Daniele , Chataway Jeremy , Chiaravalloti Nancy D , Cutter Gary , Dalgas Ulrik , DeLuca John , Farrell Rachel A , Feys Peter , Freeman Jennifer , Inglese Matilde , Meza Cecilia , Motl Robert W , Salter Amber , Sandroff Brian M , Feinstein Anthony , Filippi Massimo
Published: May 2024

Background

Research on cognitive rehabilitation (CR) and aerobic exercise (EX) to improve cognition in progressive multiple sclerosis (PMS) remains limited. CogEx trial investigated the effectiveness of CR and EX in PMS: here, we present MRI substudy volumetric and task-related functional MRI (fMRI) findings.

Methods

Participants were randomised to: ‘CR plus EX’, ‘CR plus sham EX (EX-S)’, ‘EX plus sham CR (CR-S)’ and ‘CR-S plus EX-S‘ and attended 12-week intervention. All subjects performed physical/cognitive assessments at baseline, week 12 and 6 months post intervention (month 9). All MRI substudy participants underwent volumetric MRI and fMRI (Go-NoGo task).

Results

104 PMS enrolled at four sites participated in the CogEx MRI substudy; 84 (81%) had valid volumetric MRI and valid fMRI. Week 12/month 9 cognitive performances did not differ among interventions; however, 25–62% of the patients showed Symbol Digit Modalities Test improvements. Normalised cortical grey matter volume (NcGMV) changes at week 12 versus baseline were heterogeneous among interventions (p=0.05); this was mainly driven by increased NcGMV in ‘CR plus EX-S’ (p=0.02). Groups performing CR (ie, ‘CR plus EX’ and ‘CR plus EX-S’) exhibited increased NcGMV over time, especially in the frontal (p=0.01), parietal (p=0.04) and temporal (p=0.04) lobes, while those performing CR-S exhibited NcGMV decrease (p=0.008). In CR groups, increased NcGMV (r=0.36, p=0.01) at week 12 versus baseline correlated with increased California Verbal Learning Test (CVLT)-II scores. ‘CR plus EX-S’ patients exhibited Go-NoGo activity increase (p<0.05, corrected) at week 12 versus baseline in bilateral insula.

Conclusions

In PMS, CR modulated grey matter (GM) volume and insular activity. The association of GM and CVLT-II changes suggests GM plasticity contributes to cognitive improvements.

Trial registration number

NCT03679468.
Microscopic modeling and experimental investigation of inner surface magnetorheological polishing based on particle micromechanics
Authors: Song Wanli , Hou Chenlong , Yang Shiyu , Niu Tianying , Wang Na
Published: May 2024

Traditional surface polishing methods are no longer able to meet the ultra-precision requirements of the high-tech industry for the inner surface of the pipe, but magnetorheological polishing technology is very suitable due to its advantages of high precision, fast controllability and good deposition stability. However, there is even less investigation on the microforce analysis, chaining mechanism and micromodeling methods of magnetorheological polishing fluid (MRPF), and the polishing mechanism of MRPF has not been explored yet. As a step to completely develop the magnetorheological polishing (MRP) technique, this paper proposed the simulation method of MRPF based on particle dynamics, and the shear stress model of magnetorheological fluid (MRF) is optimized under the action of the magnetic field after performing the chain simulation. On the basis of the optimized shear stress model and the hexagonal close-packed structure of MRF, the holding mechanism of polishing abrasive particles is explored for the MRPF and the corresponding holding models are proposed. Then, the shear yield stress models and material removal model are also established for the inner surface polishing, respectively. Eventually, the above theoretical analysis and related models have been verified though the polishing experiment of the titanium alloy pipe.
Deformation and Failure Evolution Law and Support Optimization of Gob‐Side Entry in Weakly Cemented Soft Rock under the Influence of Fault
Authors: Ma Chengfu , Yu Fenghai , Zhou Kai , Yang Xuerui , Sun Bo , Yao Xinyu , Chi Yani , Zhang Yuanzhi
Published: May 2024

Under the condition of weakly cemented soft rock in Western China, the surrounding rock deformation of gob‐side entry is obvious, especially under the influence of fault, and the problem of surrounding rock control becomes increasingly prominent. To solve this issue, this paper firstly studied and obtained the evolution law of the ground pressure appearance of the gob‐side entry in the fault area, then put forward the concept of surrounding rock control in the fault area of the gob‐side entry, put forward a targeted pressure relief + increase preload + passive reinforcement parallel to the roadway surrounding rock strengthening control scheme, and carried out field applications. The results show that the roof subsidence and mining side heave of the roadway in the fault area increase significantly, accompanied by the characteristics of broken cables, the length of the broken cable is 0.2 m–0.6 m, and the breaking process is divided into multiple breaks. The stress evolution of gob‐side entry in fault area presents a stage characteristic of “rapid growth‐stable.” The surrounding rock control effect is improved under the bolt cable high pre‐tightening support, and the roadway deformation is effectively controlled under the pressure relief + active + passive support, with a good application effect.
Facile Synthesis of WS2/WO3 Materials in a Batch Reactor for the Hydrogen Evolution Reaction
Authors: Nguyen Tuan Van , Huynh Kim Anh , Le Quyet Van , Ahn Sang Hyun , Kim Soo Young
Published: May 2024

In this study, a new and facile process was developed for the preparation of composite catalysts based on tungsten oxide (WO3) by batch reactor routes. The structures, morphologies, compositions, and characteristics of synthesized materials were investigated and confirmed. Using batch reactor processes, WO3 nanorods (WO3 NR), heterostructures of WS2/WO3 nanobricks (WS2/WO3 NB), and WS2/WO3 nanorods (WS2/WO3 NR) were successfully prepared. The prepared materials were then employed for hydrogen evolution reaction (HER) to investigate their catalytic performance. The results indicated that the electrocatalytic activities of WS2/WO3 NR are significantly improved compared to those of WO3 NR and WS2/WO3 NB. This improvement could be attributed to the formation of heterostructure between WS2 and WO3 elements in highly uniform materials, which could create the synergistic effect and further improve the catalytic activities of the catalyst. The data shows that the Tafel slope of WS2/WO3 NR (82.7 mV dec−1) is significantly lower than that of WO3 NR (112.5 mV dec−1) and WS2/WO3 NB (195.5 mV dec−1). Furthermore, the resistance of WS2/WO3 NR (397.7 Ω) is markedly decreased compared to those of WO3 NR (1816 Ω) and WS2/WO3 NB (3597 Ω). The results indicate that WS2/WO3 NR could be a great catalyst for electrochemical applications.
Low Serum Apolipoprotein A1 Levels Impair Antitumor Immunity of CD8+ T Cells via the HIF-1α–Glycolysis Pathway
Authors: Lv Qiaoying , Su Tong , Liu Wei , Wang Lulu , Hu Jiali , Cheng Yali , Ning Chengcheng , Shan Weiwei , Luo Xuezhen , Chen Xiaojun
Published: May 2024

An immunosuppressive microenvironment promotes the occurrence and development of tumors. Low apolipoprotein A1 (ApoA1) is closely related to tumor development, but the underlying mechanisms are unclear. This study investigated the association between serum ApoA1 levels and the immune microenvironment in endometrial, ovarian, and lung cancers. The serum ApoA1 level was decreased significantly in patients with endometrial and ovarian cancers compared with healthy controls. In endometrial cancer (EC) tissues, the low serum ApoA1 level group showed increased CD163+ macrophage infiltration and decreased CD8+ T-cell infiltration compared with the normal serum ApoA1 group. Compromised tumor-infiltrating CD8+ T-cell functions and decreased CD8+ T-cell infiltration also were found in tumor-bearing Apo1-knockout mice. CD8+ T-cell depletion experiments confirmed that ApoA1 exerted its antitumor activity in a CD8+ T-cell–dependent manner. In vitro experiments showed that the ApoA1 mimetic peptide L-4F directly potentiated the antitumor activity of CD8+ T cells via a HIF-1α–mediated glycolysis pathway. Mechanistically, ApoA1 suppressed ubiquitin-mediated degradation of HIF-1α protein by downregulating HIF-1α subunit α inhibitor. This regulatory process maintained the stability of HIF-1α protein and activated the HIF-1α signaling pathway. Tumor-bearing Apoa1 transgenic mice showed an increased response to anti–PD-1 therapy, leading to reduced tumor growth along with increased infiltration of activated CD8+ T cells and enhanced tumor necrosis. The data reported herein demonstrate critical roles for ApoA1 in enhancing CD8+ T-cell immune functions via HIF-1α–mediated glycolysis and support clinical investigation of combining ApoA1 supplementation with anti–PD-1 therapy for treating cancer.
Complications in Emergency Department Patients with Acute Coronary Syndrome with Contemporary Care
Authors: Nilsson Tsvetelina , Mokhtari Arash , Sandgren Jenny , Lundager Forberg Jakob , Olsson de Capretz Pontus , Ekelund Ulf
Published: May 2024

Introduction: With the implementation of early reperfusion therapy, the number of complications in patients with acute coronary syndrome (ACS) has diminished significantly. However, ACS patients are still routinely admitted to units with high-level monitoring such as the coronary or intensive care unit (CCU/ICU). The cost of these admissions is high and there is often a shortage of beds. The aim of this study was to analyze the complications in contemporary emergency department (ED) patients with ACS and to map patient management. Methods: This observational study was a secondary analysis of data collected in the ESC-TROP trial (NCT03421873) that included 26,545 consecutive chest pain patients ≥18 years at five Swedish EDs. Complications were defined as the following within 30 days: death, cardiac arrest, cardiogenic shock, pulmonary edema, severe ventricular arrhythmia, high-degree atrioventricular (AV) block that required a pacemaker, and mechanical complications such as papillary muscle rupture, cardiac tamponade, or ventricular septum defects (VSDs). Complications were identified via diagnosis and/or intervention codes in the database, and manual chart review was performed in cases with complications. Results: Of all 26,545 patients, 2,463 (9.3%) were diagnosed with ACS, and 151 of these (6.1%) suffered any complication within 30 days. Mean age was higher in patients with (79.2 years) than without (69.4 years) complications, and more were female (39.7% vs. 33.0%). Eighty-four (3.4% of all ACS patients) patients died, 33 (1.3%) had cardiac arrest, 22 (0.9%) respiratory failure, 13 (0.5%) high-degree AV block, 10 (0.4%) cardiogenic shock, 12 (0.5%) severe ventricular arrhythmia, and 2 each (<0.1%) had VSD or cardiac tamponade. Almost 30% of the complications were present already at the ED, and 40% of patients with complications were not admitted to the CCU/ICU. Only 80 (53%) of the patients with complications underwent coronary angiography and 62 (41%) were revascularized with percutaneous coronary intervention or coronary artery bypass grafting. Conclusion: With current care, serious complications occurred in only 6 out of 100 ACS patients, and 2 of these complications were present already at the ED. Four out of 10 ACS patients with complications were not admitted to the CCU/ICU and about half did not undergo coronary angiography. Further research is needed to improve risk assessment in ED ACS patients, which may allow more effective use of cardiac monitoring and hospital resources.
Synchronous Computed Tomography-Guided Percutaneous Transthoracic Needle Biopsy and Microwave Ablation for Highly Suspicious Malignant Pulmonary Ground-Glass Nodules
Authors: Chen Zhide , Zeng Junli , Lin Yan , Zhang Xiaoling , Wu Xuemei , Yong Yazhi , Tang Lihua , Ke Mingyao
Published: May 2024

Introduction: There is no consensus regarding the most appropriate management of suspected malignant pulmonary ground-glass nodules (GGNs). Objective: We aimed to explore the feasibility and safety of synchronous computed tomography-guided percutaneous transthoracic needle biopsy (PTNB) and microwave ablation (MWA) for patients highly suspicious of having malignant GGNs. Methods: We retrospectively reviewed medical records between July 2020 and April 2023 from our medical center. Eligible patients synchronously underwent PTNB and MWA (either MWA immediately after PTNB [PTNB-first group] or PTNB immediately after MWA [MWA-first group]) at the the physician’s discretion. We analyzed the rate of definitive diagnosis and technical success, the length of hospital stay, the postoperative efficacy, and periprocedural complications. Results: Of 65 patients who were enrolled, the rate of definitive diagnosis was 86.2%, which did not differ when stratified by the tumor size, the consolidation-to-tumor ratio, or the sequence of the two procedures (all p > 0.05). The diagnostic rate of malignancy was 83.1%. After the median follow-up duration of 18.5 months, the local control rate was 98.2% and the rate of completed ablation was 48.2%. The rate of perioperative minor and major complications was 44.6% and 6.2%, respectively. The most common adverse events included pain, cough, and mild hemorrhage. Mild hemorrhage took place significantly less frequently in the MWA-first group than in the PTNB-first group (16.7% vs. 45.5%, p < 0.05). Conclusion: Synchronous PTNB and MWA are feasible and well tolerated for patients highly suspicious of having malignant GGNs, providing an alternative option for patients who are ineligible for surgical resection.
Cell Signaling in the Circadian Pacemaker: New Insights from in vivo Imaging
Authors: Bonnefont Xavier
Published: May 2024

Background: “One for all, and all for one,” the famous rallying cry of the Three Musketeers, in Alexandre Dumas’s popular novel, certainly applies to the 20,000 cells composing the suprachiasmatic nuclei (SCN). These cells work together to form the central clock that coordinates body rhythms in tune with the day-night cycle. Like virtually every body cell, individual SCN cells exhibit autonomous circadian oscillations, but this rhythmicity only reaches a high level of precision and robustness when the cells are coupled with their neighbors. Therefore, understanding the functional network organization of SCN cells beyond their core rhythmicity is an important issue in circadian biology. Summary: The present review summarizes the main results from our recent study demonstrating the feasibility of recording SCN cells in freely moving mice and the significance of variations in intracellular calcium over several timescales. Key Message: We discuss how in vivo imaging at the cell level will be pivotal to interrogate the mammalian master clock, in an integrated context that preserves the SCN network organization, with intact inputs and outputs.