bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of type of early reflection, clarity of speech, reverberation and diffuse noise on the spatial perception of a speech source and its intelligibility
Authors: Prodi Nicola , Pellegatti Matteo , Visentin Chiara
Published: May 2022

Changing the balance between the early and late reflections in the impulse response affects the clarity of speech, and also the spatial perception of the sound source is affected when the direction of the early reflections is manipulated. While the effect of noise on early reflections has long been investigated in speech intelligibility studies, it is unclear whether and how the spatial characteristics of the source are altered by noise, and whether this would influence speech intelligibility in any way. The aim of the present work was to analyze the spatial perception of a speech source in noise and its relationship, if any, with speech intelligibility. Impulse responses with specular or scattered early reflections and two different reverberant tails were used to create sound fields with controlled clarity and reverberation. It emerged that noise affects spatial cues compared to the reverberation-only (quiet) condition; ratings are consequently changed, and most percepts are distorted. Speech intelligibility is also sensitive to changes in acoustic variables and the type of reflection, but the direct association between spatial percepts and speech intelligibility is weak.
Multistable shape programming of variable-stiffness electromagnetic devices
Authors: Aksoy Bekir , Shea Herbert
Published: May 2022

Programmable shape morphing enables soft machines to safely and effectively interact with the environment. Stimuli-responsive materials can transform 2D sheets into 3D geometries. However, most solutions cannot hold their shape at zero power, are limited to predetermined configurations, or lack sufficient mechanical stiffness to manipulate common objects. We demonstrate here segmented soft electromagnetic actuators integrated with shape memory polymer (SMP) films, capable of deforming and latching into a broad range of configurations. The device consists of liquid metal (LM) coils in an elastomer shell, laminated between two SMP films. The coils are linked by narrow joints, on which stretchable heaters are patterned. Heating the SMP greatly reduces its stiffness. Driving current through an LM coil in the presence of a magnetic field then leads to large bending or twisting. Cooling the SMP locks in the shape, leading to load-bearing capacity. Complex shapes are obtained from an initially flat device.
Development of oil-based gels as versatile drug delivery systems for pediatric applications
Authors: Kirtane Ameya R. , Karavasili Christina , Wahane Aniket , Freitas Dylan , Booz Katelyn , Le Dao Thi Hong , Hua Tiffany , Scala Stephen , Lopes Aaron , Hess Kaitlyn , Collins Joy , Tamang Siddartha , Ishida Keiko , Kuosmanen Johannes L. P. , Rajesh Netra Unni , Phan Nhi V. , Li Junwei , Krogmann Annlyse , Lennerz Jochen K. , Hayward Alison , Langer Robert , Traverso Giovanni
Published: May 2022

Administering medicines to 0- to 5-year-old children in a resource-limited environment requires dosage forms that circumvent swallowing solids, avoid on-field reconstitution, and are thermostable, cheap, versatile, and taste masking. We present a strategy that stands to solve this multifaceted problem. As many drugs lack adequate water solubility, our formulations used oils, whose textures could be modified with gelling agents to form “oleogels.” In a clinical study, we showed that the oleogels can be formulated to be as fluid as thickened beverages and as stiff as yogurt puddings. In swine, oleogels could deliver four drugs ranging three orders of magnitude in their water solubilities and two orders of magnitude in their partition coefficients. Oleogels could be stabilized at 40°C for prolonged durations and used without redispersion. Last, we developed a macrofluidic system enabling fixed and metered dosing. We anticipate that this platform could be adopted for pediatric dosing, palliative care, and gastrointestinal disease applications.
Chemodivergent Csp
3
─F bond functionalization and cross-electrophile alkyl-alkyl coupling with alkyl fluorides
Authors: Balaraman Kaluvu , Wolf Christian
Published: May 2022

The widespread use of fluorinated organic compounds in the health, agrochemical, and materials sciences is sustained by a steadily growing pool of commercially available fine chemicals. The synthetic utility of the increasingly ubiquitous Csp
3
─F bond, however, remains to be fully exploited, which is often a difficult task because of its paramount stability and chemical inertness. Here, we demonstrate chemodivergent activation of monofluoroalkyl compounds toward either nucleophilic or electrophilic intermediates. This is accomplished under conditions that are compatible with several reaction types and many functional groups, which drastically widens the current scope of organofluorine chemistry and sets the stage for carbon-carbon and carbon-heteroatom bond formations, stereoselective construction of bisoxindole alkaloid scaffolds via in situ Umpolung, and cross-electrophilic coupling methodology. The selective generation of either nucleophilic or electrophilic species and the possibility of doing so simultaneously or, alternatively, switching molecular polarity enable previously unidentified synthetic opportunities that recognize alkyl fluorides as chemodivergent building blocks.
Fixture-free omnidirectional prestretching fabrication and integration of crumpled in-plane micro-supercapacitors
Authors: Wang Ying , Zhao Yang , Han Yuyang , Li Xiangyang , Dai Chunlong , Zhang Xinqun , Jin Xuting , Shao Changxiang , Lu Bing , Wang Chengzhi , Cheng Huhu , Liu Feng , Qu Liangti
Published: May 2022

Multidimensional folded structures with elasticity could provide spatial charge storage capability and shape adaptability for micro-supercapacitors (MSCs). Here, highly crumpled in-plane MSCs with superior conformality are fabricated in situ and integrated by a fixture-free omnidirectional elastic contraction strategy. Using carbon nanotube microelectrodes, a single crumpled MSC holds an ultrahigh volumetric capacitance of 9.3 F cm
−3
, and its total areal capacitance is 45 times greater than the initial state. Experimental and theoretical simulation methods indicate that strain-induced improvements of adsorption energy and conductance for crumpled microelectrodes are responsible for the prominent enhancement of electrochemical performance. With outstanding morphological randomicity, the integrated devices can serve as smart coatings in moving robots, withstanding extreme mechanical deformations. Notably, integration on a spherical surface is possible by using a spherical mask, in which a small area of the microdevice array (3.9 cm
2
) can produce a high output voltage of 100 V.
Supplemental Material: Middle Jurassic intracontinental evolution of East Asia: Insights from the Tianshifu-Dongyingfang basin of the Liaodong Peninsula, NE China
Authors: Ren Zhiheng , Dong Shuwen , al. et
Published: May 2022

Table S1. LA-ICP-MS zircon U-Pb data of the samples from the Tianshifu-Dongyingfang basin.
Paradoxical embolisation in right-sided infective endocarditis and patent foramen ovale
Authors: Shimfessel Tyler T , El-Dalati Sami A , Sekela Michael , Ahmed Taha
Published: May 2022

Intravenous drug use (IVDU) is a growing public health crisis worldwide. A known complication of IVDU is right-sided infective endocarditis (RSIE) involving the tricuspid valve. As the tricuspid valve is burdened with infectious vegetations, it becomes a potential source of pulmonary and, very rarely, paradoxical systemic emboli. We report two patients with RSIE involving the tricuspid valve presenting with acute change in mental status. Subsequent imaging demonstrated embolisation to the brain in the setting of elevated right atrial pressures and the presence of a patent foramen ovale (PFO) with right-to-left shunting. We employed a strategy of percutaneous closure of PFO, to prevent further embolisation, as a successful bridge to definitive surgical management of RSIE. We emphasise that clinicians should evaluate for intracardiac shunting and pursue transesophageal echocardiography when encountering systemic emboli of unknown origin, particularly in patients with RSIE.
Crying baby gets the milk? The governmentality of grievance redressal for patient rights violations in Karnataka, India
Authors: Putturaj Meena , Krumeich Anja , Nuggehalli Srinivas Prashanth , Engel Nora , Criel Bart , Van Belle Sara
Published: May 2022

Background

Patient rights aim to protect the dignity of healthcare-seeking individuals. Realisation of these rights is predicated on effective grievance redressal for the victims of patient rights violations.

Methods

We used a critical case (that yields the most information) of patient rights violations reported in Karnataka state (South India) to explore the power dynamics involved in resolving grievances raised by healthcare-seeking individuals. Using interviews, media reports and other documents pertaining to the case, we explored the ‘governmentality’ of grievance redressal for patient rights violations, that is, the interaction of micropractices and techniques of power employed by actors to govern the processes and outcomes. We also examined whether existing governmentality ensured procedural and substantive justice to care-seeking individuals.

Results

Collective action was necessary by the aggrieved women in terms of protests, media engagement, petitions and follow-up to ensure that the State accepted a complaint against a medical professional. Each institution, and especially the medical professional council, exercised its power by problematising the grievance in its own way which was distinct from the problematisation of the grievance by the collective. The State bureaucracy enacted its power by creating a maze of organisational units and by fragmenting the grievance redressal across various bureaucratic units.

Conclusion

There is a need for measures guaranteeing accountability, transparency, promptness, fairness, credibility and trustworthiness in the patient grievance redressal system. Governmentality as a framework enabled to study how subjects (care-seeking individuals) are rendered governable and resist dominant forces in the grievance redressal system for patient rights violations.
Lessons learnt from applying a human-centred design process to develop one of the largest mobile health communication programmes in the world
Authors: Chamberlain Sara , Dutt Priyanka , Mitra Radharani , Godfrey Anna , LeFevre Amnesty E , Scott Kerry , Katiyar Soma , Mendiratta Jai , Chaturvedi Shefali
Published: May 2022

‘Design with the user’ is a guiding principle for creating digital solutions to solve systemic developmental challenges. According to this principle, digital solutions are more likely to be effective if the intended users are involved in the design process, thereby rooting design thinking in a human-centric approach that seeks to understand their characteristics, needs and challenges. However, few examples exist for human-centred design (HCD) processes being successfully applied in low-and-middle-income countries to create digital health interventions that achieve both scale and sustainability. This paper describes the application of a five-stage HCD process to develop a suite of mobile solutions to improve reproductive, maternal, neonatal and child health in Bihar, India, and discusses lessons learnt. Two of the solutions were later adopted by the government and scaled to 10 million subscribers and more than 300 000 front-line health workers (FLHWs) in 13 states. The socio-ecological model, which considers the interplay between individual, interpersonal, organisational, community and public policy factors, provides a conceptual framework for understanding key learnings from the HCD process. At the organisational level, we found that demand generation was constrained by deficiencies in the public health system, while at the community level, gender norms were a barrier to changing health practices. At the interpersonal level, mobile health solutions for mothers also had to address fathers, because they controlled women’s access to mobile phones. At the individual level, FLHWs had limited time to build their skills and needed more flexible, home-based learning opportunities; most FLHWs had access to mobile phones, but devices were overwhelmingly basic and digital skills limited; voice technology was required to maximise reach among low literate women and an authoritative yet empathetic narrator was required to humanise the digital experience, lend credibility and create engagement.
Triple-negative breast cancer prevalence in Africa: a systematic review and meta-analysis
Authors: Hercules Shawn M , Alnajar Meena , Chen Chen , Mladjenovic Stefan M , Shipeolu Bolade Ajarat , Perkovic Olga , Pond Greg R , Mbuagbaw Lawrence , Blenman Kim RM , Daniel Juliet M
Published: May 2022

Objective

The aggressive triple-negative breast cancer (TNBC) subtype disproportionately affects women of African ancestry across the diaspora, but its frequency across Africa has not been widely studied. This study seeks to estimate the frequency of TNBC among African populations.

Design

Systematic review and meta-analysis using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework.

Data sources

PubMed, EMBASE, African Journals Online and Web of Science were searched on 25 April 2021.

Eligibility criteria for selecting studies

We included studies that use breast cancer tissue samples from indigenous African women with sample size of eligible participants ≥40 and full receptor status for all three receptors (oestrogen receptor (ER)/progesterone receptor (PR)/human epidermal growth factor receptor 2 (HER2)) reported.

Data extraction and synthesis

Two independent reviewers extracted data and assessed risk of bias using the modified assessment tool by Hoy et al. (2012) for prevalence studies. A random-effects meta-analysis was performed, and data were pooled using the inverse-variance method and logit transformation. Pooled frequencies were reported with 95% CIs calculated with the Clopper-Pearson method and heterogeneity quantified with I2 statistic. GRADE assessed the certainty of the evidence.

Results

1808 potentially eligible studies were identified of which 67 were included in the systematic review and 60 were included in the meta- analysis. Pooled TNBC frequency across African countries represented was estimated to be 27.0%; 95% CI: 24.0% to 30.2%, I2=94%. Pooled TNBC frequency was highest across West Africa, 45.7% (n=15, 95% CI: 38.8% to 52.8%, I2=91%) and lowest in Central Africa, 14.9% (n=1, 95% CI: 8.9 % to 24.1%). Estimates for TNBC were higher for studies that used Allred guidelines for ER/PR status compared with American Society of Clinical Oncology(ASCO)/College of American Pathologists(CAP) guidelines, and for studies that used older versions of ASCO/CAP guidelines for assessing HER2 status. Certainty of evidence was assessed to be very low using GRADE approach.

Conclusion

TNBC frequency was variable with the highest frequency reported in West Africa. Greater emphasis should be placed on establishing protocols for assessing receptor status due to the variability among studies.
Allostatic load as predictor of mortality: a cohort study from Lolland-Falster, Denmark
Authors: Bruun-Rasmussen Neda Esmailzadeh , Napolitano George , Christiansen Christian , Bojesen Stig Egil , Ellervik Christina , Jepsen Randi , Rasmussen Knud , Lynge Elsebeth
Published: May 2022

Objectives

The purposes of the present study were to determine the association between (1) 10 individual biomarkers and all-cause mortality; and between (2) allostatic load (AL), across three physiological systems (cardiovascular, inflammatory, metabolic) and all-cause mortality.

Design

Prospective cohort study.

Setting

We used data from the Lolland-Falster Health Study undertaken in Denmark in 2016–2020 and used data on systolic blood pressure (SBP) and diastolic blood pressure (DBP), pulse rate (PR), waist–hip ratio (WHR) and levels of low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), triglycerides, glycated haemoglobin A1c (HbA1c), C-reactive protein (CRP) and serum albumin. All biomarkers were divided into quartiles with high-risk values defined as those in the highest (PR, WHR, triglycerides, HbA1c, CRP) or lowest (HDL-c, albumin) quartile, or a combination hereof (LDL-c, SBP, DBP). The 10 biomarkers were combined into a summary measure of AL index. Participants were followed-up for death for an average of 2.6 years.

Participants

We examined a total of 13 725 individuals aged 18+ years.

Primary outcome measure

Cox proportional hazard regression (HR) analysis were performed to examine the association between AL index and mortality in men and women.

Results

All-cause mortality increased with increasing AL index. With low AL index as reference, the HR was 1.33 (95% CI: 0.89 to 1.98) for mid AL, and HR 2.37 (95% CI: 1.58 to 3.54) for high AL.

Conclusions

Elevated physiological burden measured by mid and high AL index was associated with a steeper increase of mortality than individual biomarkers.
Internet-based support for informal caregivers to individuals with head and neck cancer (Carer eSupport): a study protocol for the development and feasibility testing of a complex online intervention
Authors: Langegård Ulrica , Cajander Åsa , Carlsson Maria , von Essen Louise , Ahmad Awais , Laurell Göran , Tiblom Ehrsson Ylva , Johansson Birgitta
Published: May 2022

Introduction

It is strongly recommended that randomised controlled trials are preceded with an exploration of the needs of the target population and feasibility testing of the intervention. The present study protocol is set out to describe these steps in the development of a complex intervention.

The past decades’ transition of care from inpatient to outpatient settings has increased the complexity of caregivers’ responsibilities, which they may not be prepared for. There is a need to support informal caregivers (ICs) to prepare them for caregiving and decrease the caregiver burden. The main aim of this study is to describe the development of an internet-based intervention (Carer eSupport) to improve ICs’ ability to support individuals with head and neck cancer and to describe the testing of the feasibility and acceptability of Carer eSupport.

Methods and analysis

This is a multicentre study involving the ear, nose and throat clinics and the oncology and radiotherapy clinics at three university hospitals. The study protocol comprises two phases, development and feasibility testing, using the Medical Research Council framework for developing a complex intervention. Carer eSupport will be based on the results from focus group discussions with ICs and healthcare professionals (planned for n=6–8 in respective groups) and scientific evidence, the Social Cognitive Theory and the Theory of Acceptance and Use of Technology. The feasibility testing will include 30 ICs who will have access to Carer eSupport for 1 month. The feasibility testing will be evaluated with a mixed-method design.

Ethics and dissemination

All procedures have been approved by the Ethics Committee at Uppsala University (Dnr: 2020-04650). Informed consent will be obtained before enrolment of patients, their ICs and healthcare staff. The feasibility testing is registered at Clinicaltrials.gov (Identifier: NCT05028452). Findings will be disseminated in peer-reviewed journal publications.

Trial registration number

Clinicaltrials.gov (Identifier: NCT05028452).
Implementation of the Diabetes Community Exercise and Education Programme (DCEP) for the management of type 2 diabetes: qualitative process evaluation
Authors: Stokes Tim , Wilkinson Amanda , Jayakaran Prasath , Higgs Christopher , Keen Donna , Mani Ramakrishnan , Sullivan Trudy , Gray Andrew R , Doolan-Noble Fiona , Mann Jim , Hale Leigh
Published: May 2022

Objectives

To examine context-specific delivery factors, facilitators and barriers to implementation of the Diabetes Community Exercise and Education Programme (DCEP) for adults with type 2 diabetes (T2D) using the Reach, Effectiveness, Adoption, Implementation and Maintenance framework.

Design

A qualitative evaluation embedded within the DCEP pragmatic randomised controlled trial. Data collected via focus groups and interviews and analysed thematically.

Setting

Community-based in two cities (Dunedin and Invercargill) in the lower south island of New Zealand.

Participants

Seventeen adults diagnosed with T2D attending DCEP and 14 healthcare professionals involved in DCEP delivery.

Intervention

DCEP is a twice weekly session of exercise and education over 12 weeks, followed by a twice weekly ongoing exercise class.

Results

While our reach target was met (sample size, ethnic representation), the randomisation process potentially deterred Māori and Pasifika from participating. The reach of DCEP may be extended through the use of several strategies: promotion of self-referral, primary healthcare organisation ownership and community champions. DCEP was considered effective based on perceived benefit. The social and welcoming environment created relationships and connections. People felt comfortable attending DCEP and empowered to learn. Key to implementation and adoption was the building of trusting relationships with local health providers and communities. This takes time and care and cannot be rushed. Training of staff and optimising communication needed further attention. To maintain DCEP, delivery close to where people live and a generic approach catering for people with multiple chronic conditions may be required.

Conclusions

For success, lifestyle programmes such as DCEP, need time and diligence to build and maintain networks and trust. Beyond frontline delivery staff and target populations, relationships should extend to local healthcare organisations and communities. Access and ongoing attendance are enabled by healthcare professionals practicing in a nuanced person-centred manner; this, plus high staff turnover, necessitates ongoing training.

Trial registration number

ACTRN12617001624370.
Cohort profile: the Swedish Pancreatitis Cohort (SwePan)
Authors: Selin Daniel , Yang Bei , Lindblad Mats , Arnelo Urban , Nilsson Magnus , Sadr-Azodi Omid , Maret-Ouda John
Published: May 2022

Purpose

The Swedish Pancreatitis Cohort (SwePan) was designed to study long-term outcomes following an episode of acute pancreatitis. It can also be used to study various risk factors for developing acute pancreatitis.

Participants

The SwePan is a register-based nationwide matched cohort. It includes all Swedish cases of acute pancreatitis during 1990–2019. It contains 95 632 individuals with acute pancreatitis and 952 783 pancreatitis-free individuals matched on sex, age and municipality of residence. Follow-up was censored at death, emigration or end of study (31 December 2019). The dataset includes comprehensive information based on several registries, and includes diagnoses, prescribed medications and socioeconomic factors both prior to inclusion and during follow-up.

Findings to date

During the study period, the number of cases of acute pancreatitis in Sweden has more than doubled from 1977 cases in 1990 to 4264 cases in 2019. The median age of first episode of acute pancreatitis has increased from 58 years (IQR 44–73 years) in 1990 to 64 years (IQR 49–76 years) in 2019. Cases with acute pancreatitis were generally less healthy compared with the pancreatitis-free individuals (Charlson Comorbidity Index of 0 in 59.2% and 71.4%, respectively).

Future plans

SwePan will be used to determine the incidence of acute pancreatitis in Sweden over time and assess long-term all-cause and cause-specific mortality after an episode of acute pancreatitis. Some examples of additional planned studies are (1) assessment of long-term risk of diabetes and (2) risk of malignancy in adjacent organs following acute pancreatitis and (3) assessment of risk factors for development of acute pancreatitis including various drugs.
Evaluating the impact of a maternity and neonatal emergencies education programme in Australian regional and rural health services on clinician knowledge and confidence: a pre-test post-test study
Authors: Cullinane Meabh , Zugna Stefanie A , McLachlan Helen L , Newton Michelle S , Forster Della A
Published: May 2022

Introduction

Almost 78 000 women gave birth in the state of Victoria, Australia, in 2019. While most births occurred in metropolitan Melbourne and large regional centres, a significant proportion of women birthed in rural services. In late 2016, to support clinicians to recognise and respond to clinical deterioration, the Victorian government mandated provision of an emergency training programme, called Maternity and Newborn Emergencies (MANE), to rural and regional maternity services across the state. This paper describes the evaluation of MANE.

Design and setting

A quasi-experimental study design was used; the Kirkpatrick Evaluation Model provided the framework.

Participants

Participants came from the 17 rural and regional Victorian maternity services who received MANE in 2018 and/or 2019.

Outcome measures

Baseline data were collected from MANE attendees before MANE delivery, and at four time points up to 12 months post-delivery. Clinicians’ knowledge of the MANE learning objectives, and confidence ratings regarding the emergencies covered in MANE were evaluated. The Safety Attitudes Questionnaire (SAQ) assessed safety climate pre-MANE and 6 months post-MANE among all maternity providers at the sites.

Results

Immediately post-MANE, most attendees reported increased confidence to escalate clinical concerns (n=251/259). Knowledge in the non-technical and practical aspects of the programme increased. Management of perinatal emergencies was viewed as equally stressful pre-MANE and post-MANE, but confidence to manage these emergencies increased post-delivery. Pre-MANE SAQ scores showed consistently strong and poor performing services. Six months post-MANE, some services showed improvements in SAQ scores indicative of improved safety climate.

Conclusion

MANE delivery resulted in both short-term and sustained improvements in knowledge of, and confidence in, maternity emergencies. Further investigation of the SAQ across Victoria may facilitate identification of services with a poor safety climate who could benefit from frequent targeted interventions (such as the MANE programme) at these sites.
Current status of medical device malfunction reporting: using end user experience to identify current problems
Authors: Tase Arkeliana , Ni Melody Z , Buckle Peter W , Hanna George B
Published: May 2022

Introduction

The current under-reporting of medical device malfunctions, difficulties with the current system and absence of continuous good-quality data has removed the possibility for constant data interrogation and trend recognition to identify evolving issues. This research used end user experiences aiming to understand causes for the lack of data and knowledge on device performance and associated patient risks. This approach was used to identify existing barriers and methods for improvement.

Methods

This is a qualitative study involving semistructured interviews and surveys with clinicians (15 interviews, 39 surveys) and manufacturers (13 interview participants, 5 surveys). Multiple sources of recruiting were used. Data collected were thematically analysed. Interview results were used to design the surveys. Standards for Reporting Qualitative Research was used.

Results

Medical device use is based on personal experience rather than evidence which is scarce. Multiple barriers to reporting were identified alongside patient safety and system related aspects. Furthermore, the acceptable level of error was variable as were effects on working practice. Many workarounds have been developed to overcome problems and have become normalised in daily work. These factors were found to have a limiting impact on improvements and learning. Greater system transparency, feedback on submitted reports, a more efficient system of reporting and better communication with manufacturers were reported as some of the required improvements.

Conclusions

This study has identified numerous complex issues affecting reporting of medical device performance and their subsequent effect on patient safety and clinical staff. The focus on incidents has created many limitations to learning and development. The rich experience of end users should be appropriately used to identify system weaknesses and seek improvement methods. Better communication methods should be developed between healthcare and MedTech (Medical Technologies) industry.
Personalised multicomponent interventions for tobacco dependence management in low socioeconomic populations: a systematic review and meta-analysis
Authors: Huynh Nina , Tariq Saania , Charron Catherine , Hayes Tavis , Bhanushali Onkar , Kaur Tina , Jama Sadia , Ambade Preshit , Bignell Ted , Hegarty Terry , Shorr Risa , Pakhale Smita
Published: May 2022

Background

There remains a disproportionally high tobacco smoking rate in low-income populations. Multicomponent tobacco dependence interventions in theory are effective. However, which intervention components are necessary to include for low socioeconomic status (SES) populations is still unknown.

Objective

To assess the effectiveness of multicomponent tobacco dependence interventions for low SES and create a checklist tool examining multicomponent interventions.

Methods

EMBASE and MEDLINE databases were searched to identify randomised controlled trials (RCTs) published with the primary outcome of tobacco smoking cessation measured at 6 months or post intervention. RCTs that evaluated tobacco dependence management interventions (for reduction or cessation) in low SES (experience of housing insecurity, poverty, low income, unemployment, mental health challenges, illicit substance use and/or food insecurity) were included. Two authors independently abstracted data. Random effects meta-analysis and post hoc sensitivity analysis were performed.

Results

Of the 33 included studies, the number of intervention components ranged from 1 to 6, with smoking quit rates varying between 1% and 36.6%. Meta-analysis revealed that both the 6-month and 12-month outcome timepoints, multicomponent interventions were successful in achieving higher smoking quit rates than the control (OR 1.64, 95% Cl 1.41 to 1.91; OR 1.74, 95% Cl 1.30 to 2.33). Evidence of low heterogeneity in the effect size was observed at 6-month (I2=26%) and moderate heterogeneity at 12-month (I2=56%) outcomes.

Conclusion

Multicomponent tobacco dependence interventions should focus on inclusion of social support, frequency and duration of components. Employing community-based participatory-action research approach is essential to addressing underlying psychosocioeconomic-structural factors, in addition to the proven combination pharmacotherapies.

PROSPERO registration number

CRD42017076650.
Phase II trial of efficacy, safety and biomarker analysis of sintilimab plus anlotinib for patients with recurrent or advanced endometrial cancer
Authors: Wei Wei , Ban Xiaohua , Yang Fan , Li Jibin , Cheng Xiaqin , Zhang Rong , Huang Xin , Huang Yongwen , Li Qiaqia , Qiu Ya , Zheng Min , Zhu Xiaofeng , Li Jundong
Published: May 2022

Background

Although co-inhibition of the angiogenesis and programmed death 1 (PD-1) pathways is proposed as an effective anticancer strategy, studies in Chinese patients with endometrial cancer are sufficient. Anlotinib is an oral multi-targeted tyrosine kinase inhibitor affecting tumor angiogenesis and proliferation; sintilimab is an anti-PD-1 monoclonal antibody.

Methods

This was a phase II trial using Simon’s two-stage design. This study enrolled patients with endometrial cancer who had progressed after platinum-based chemotherapy. Sintilimab 200 mg was administered intravenously on day 1 every 3 weeks, and anlotinib 12 mg was administered on days 1–14 in a 21-day cycle. The primary endpoint was the objective response rate (ORR) using the immune-related Response Evaluation Criteria in Solid Tumors criteria. Immunohistochemistry and whole-exome sequencing were used as correlative investigations.

Results

Between November 2019 and September 2020, 23 eligible patients were enrolled. The ORR and disease control rates were 73.9% (95% CI, 51.6 to 89.8) and 91.3% (95% CI, 72.0 to 98.9), respectively, with 4 complete and 12 partial responses. With a median follow-up of 15.4 months (95% CI, 12.6 to 18.3), the median progression-free survival was not reached, and the probability of PFS >12 months was 57.1% (95% CI, 33.6 to 75.0). Exploratory analysis revealed that mutations in the homologous repair pathway showed a trend for higher ORR (100% vs 0%, p=0.07). Treatment-related grade 3/4 adverse events were observed in 50.0% of the patients.

Conclusions

Sintilimab plus anlotinib demonstrated robust therapeutic benefits with tolerable toxicity in endometrial cancer.

Trial registration number

NCT04157491.
064  Imilimumab/nivolumab induced paraspinal myositis causing dysphagia
Authors: Warner Graham
Published: May 2022

Immune checkpoint inhibitors have transformed metastatic melanoma treatment. Imilimumab/Nivolumab combination increases progression-free survival [1], but Imilimumab can cause immune-related condi- tions including hepatitis, colitis and dermatitis[2]. We present a case of Imilimumab/Nivolumab-induced posterior paraspinal muscles myositis.

A 78 year-old man with metastatic melanoma with hepatic, osseous, and lymph node spread had 3 weeks of dysphagia to solids but not liquids, 2 months after his last cycle of immunotherapy. He complained of hoarse voice, weight loss, unsteadiness and falls.

Examination revealed symmetrical, normal palatal rise without tongue wasting or fasciculation. Speech was hypernasal with poor pharyngeal phonation. There was no fatigue nor ptosis nor extra-ocular motor weakness. Small muscle hand wasting was modest in keeping with general cachexia. Power in all limbs was preserved with no fasciculation.

CK was mildly elevated at 522 u/l. Brain MRI showed a normal brain stem with scant cerebral white matter ischaemia. Neck imaging showed no pharyngeal infiltration but extensive muscular oedema involving trapezii and para-spinal muscles (skull base to sacrum), consistent with myositis secondary to immunotherapy.

He received 13 days Methylprednisolone 2mg/kg and speech and swallow improved markedly on serial SALT assessments.

Inflammatory myopathy is recognised with novel metastatic melanoma treatments, others reporting dysphagia[3] or limb-girdle weakness[4]. Our case highlights the evolving recognition of immunotherapy side effects and awareness for myositis in these patients.

graham.warner@nhs.net
066  Clinical and imaging findings in MOG antibody positive patients presenting to Kings College Hospital
Authors: Raftopoulos Rhian , Williams Victoria , Brex Peter , O’Sullivan Eoin
Published: May 2022

We identified all patients testing positive for MOG antibodies at KCH and reviewed their clinical phenotype and imaging findings. 22 patients tested positive for MOG antibodies between Jan 2015 and Aug 2019 (11 female, mean age 39 (SD 18)). The majority of patients 15/22 presented with optic neuritis, 3 patients bilateral, 2 bilateral sequential. Other presentations included LETM (2), ADEM(2), brain stem syndrome (1), lower cord/conus syndrome (1) seizures (1). Mean logMar visual acuity at nadir in patients present- ing with an optic neuritis was 0.69 (SD 0.58). Mean logMar visual acuity at recovery was logMAR 0.1 (SD 0.54), 12/15 eyes had documented optic disc swelling. MRI brain was performed in 20 patients and was normal in 10, 6 had non-specific white matter changes the remainder had inflammatory brainstem and ADEM –like changes. MRI orbits was performed in 13 patients, 4 had bilateral optic nerve involvement and 5 had longitudinally extensive optic nerve lesions. Spinal cord imaging was performed in 9 patients, 2 had a LETM, 1 multifocal signal change and the remainder normal imaging. The cervical cord was the most frequently involved region of the spinal cord. 5 patients developed relapses (all optic neuritis), 3 relapses occurred off treatment.

r.raftopoulos@ucl.ac.uk
072  The oblique path of a transverse lesion
Authors: Kesserwani Jad , Cooper Rebecca , Wickremaratchi Mirdhu , Palace Jaqueline , Fisniku Leonora
Published: May 2022

A 38-year-old man presented in September 2016 with left hand numbness which progressed over 2 days to disabling weakness of his left arm and leg. He initially presented to a stroke unit, stroke being ruled out by brain MRI. An MRI spine showed an intramedullary lesion extending from C2-C7. He was referred to neurosurgery who queried an astrocytoma and performed a biopsy. Biopsy demonstrated a demyelinat- ing lesion leading to referral to neurology.

Following a battery of investigations, visual evoked potentials showed left sided delay and positive serum aquaporin-4 antibodies (AQP4-Abs). A diagnosis of Neuromyelitis Optica Spectrum Disorder (NMOSD) was made.

He received dexamethasone and his symptoms dramatically improved. He deteriorated on weaning but responded well to subsequent plasma exchange.

He remained clinically and radiologically stable on azathioprine and prednisolone until Spring 2019 before suffering two clinical and radiological relapses. Both relapses involved sensory disturbance and mild weakness in his left upper and lower limbs, responding to pulsed methylprednisolone. Rituximab treatment is being set up.

This case highlights that NMOSD can mimic both stroke and spinal cord tumour and needs to be con- sidered in similar presentations to avoid unnecessary morbidity from cord biopsy, and to enable prompt initiation of immunotherapeutic treatment.

Rebeccacooper@doctors.org.uk
076  Increased physiological responses to threat in Duchenne muscular dystrophy: a potential CNS outcome measure
Authors: Maresh Kate E , Papageorgiou Andriani , Ridout Deborah , Harrison Neil A , Mandy William , Skuse David , Muntoni Francesco
Published: May 2022

Dystrophin is expressed in brain as well as muscle, and its loss in Duchenne muscular dystrophy (DMD) causes CNS disturbance in addition to muscle pathology. A DMD mouse model (mdx) exhibits exagger- ated fear responses to threat, which normalise with postnatal dystrophin-restoration therapies.

To investigate whether fear responses are abnormal in DMD patients, we tested 31 DMD and 25 male control participants aged 7–12 years using a fear conditioning task. Participants viewed trials of two neutral visual stimuli: one ‘safe’ stimulus and one paired with a ‘threat’ (aversive noise) to enable fear condi- tioning. Both stimuli were subsequently presented without the noise to assess extinction of conditioned autonomic fear responses (skin conductance).

The initial (unconditioned) response to threat was significantly greater in DMD than controls (p=0.016). Both groups similarly acquired conditioned fear responses (p=0.55). These were retained in controls during early extinction, and later extinguished, however DMD participants showed no significant discrimination between threat/safe stimuli in extinction.

This study is the first to investigate fear responses in DMD boys, showing exaggerated unconditioned responses to threat, similar to mdx mice, and abnormalities of fear extinction. Establishing this objective measure of a potentially reversible CNS phenotype will benefit clinical trials of CNS-targeted dystrophin- restoration therapies.

drkatemaresh@gmail.com
102  The cost of misdiagnosis in POEMS syndrome
Authors: Keddie Stephen , Marsh Eleanor , D’Sa Shirley , Terris-Prestholt Fern , Lunn Michael
Published: May 2022

Background

POEMS syndrome is a rare cause of neuropathy misdiagnosed as Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) in 60% of cases. Ineffective CIDP directed therapy is expensive, introduces risk of complications, and often results in disease progression. Vascular endothelial growth factor (VEGF) is a sensitive and specific biomarker in the diagnosis of POEMS syndrome costing approximately £50. Introducing early directed screening with VEGF more accurately distinguishes POEMS syndrome from CIDP than the current standard of care (SOC).

Methods

100 cases from the UCLH POEMS database were selected. We grouped patients according to diagnostic pathway and compared health outcomes. We conducted a model-based cost-effectiveness analysis to compare diagnostic outcomes and costs of the current SOC with intervention pathways using VEGF screening. We used a study cohort of 1,250 patients with polyneuropathy (UK incidence) and conducted costing from a health-services perspective.

Results

Treatments associated with POEMS misdiagnosis led to a total healthcare expenditure in our cohort of £808,550-£1,111,756 over 20 years, with an average cost-per-POEMS-syndrome-patient misdiagnosed of

£14,701-£20,214. Our intervention pathway which introduces VEGF screening into the current SOC results in 4 additional early POEMS diagnoses per year and a cost-saving of almost £40,000 through avoidance of non-POEMS directed therapy and related hospital costs.

Conclusion

VEGF testing should be routine for patients presenting with an acquired demyelinating neu- ropathy. This will improve early diagnosis of POEMS syndrome, enable effective therapy and reduce cos8ts5.

stephen.keddie@nhs.net
106  Inflammatory peripheral neuropathy in haematological malignancies
Authors: Zirra Alexandra , Baheerathan Aravindhan , D’Sa Shirley , Lunn Michael
Published: May 2022

Background

We report the case of a 62-year-old female with demyelinating sensorimotor polyneuropathy in the context of lymphoplasmacytic lymphoma.

Case Presentation

62-year-old woman presenting with distal lower limb numbness bilaterally, with a 9-year progressive course. Over the next 3 years, foot drop developed with gradual lower and upper limb involvement.

Investigations showed raised IgM paraprotein, 20 g/dL. Bone marrow biopsy identified 2-B cell clonal populations with positive MYD88 mutation in keeping with lymphoplasmacytic lymphoma (LPL). Neuro- physiological studies showed very severe length-dependent, sensorimotor neuropathy. She was VEGF/anti-MAG negative, but anti-GM2 positive. Widely-spaced myelin and moderate axonal loss were seen on sural nerve biopsy.

She was diagnosed with a progressive demyelinating neuropathy in the context of LPL.

Initial IVIG treatment failed.

Second line treatment – cyclophosphamide/rituximab/dexamethasone, improved her lower limb weakness. Ibrutinib later stabilised her weakness in the lower but not upper limbs.

Plexus nerve biopsy showed general inflammation, excluding direct clonal infiltration and amyloid deposi- tion. This reconfirmed the diagnosis: inflammatory neuropathy driven by a haematological malignancy. She received further treatment with rituximab-bendamustine.

Conclusion

Understanding the pathological mechanism of polyneuropathies in haematological malignan- cies is of paramount importance for choosing the most effective therapy, as illustrated by the above cas8e7.

a.zirra@nhs.net
117  The role of the cerebellum in cortical myoclonus: a neurophysiological study
Authors: Latorre Anna , Rocchi Lorenzo , Rothwell John , Bhatia Kailash
Published: May 2022

Objective

To investigate whether primary writing tremor (PWT) and dystonia share a common pathophysiology.

Background

PWT is probably the most common form of task-specific tremor. Its pathophysiology is still debated and there is controversy about it being a type of focal dystonia, a variant of essential tremor or a separate entity.

Methods

We recruited 7 patients with PWT, who underwent the following neurophysiological tests: blink recovery cycle (BRC), eye-blink classical conditioning (EBCC), short and long-intracortical inhibition (SICI-LICI). Moreover, motor-evoked potentials (MEP), SICI and LICI were measured pre and post paired associative stimulation (PAS) plasticity paradigm. Data were compared with those obtained in 7 dystonic patients (DYT).

Results

Data analysis for BRC showed a similar inhibition between DYT and PWT. There was no difference between DYT and PWT in the number of conditioned response (CR) during. Baseline SICI and LICI were similar in the two patients’ group, but whereas they were unchanged in PWT after PAS, they were reduced in DYT.

Conclusions

The present results suggest that PWT and DYT have similar brainstem excitability and associative learning. Cortical plasticity induced by PAS had a different effect on SICI and LICI in the two groups. Overall this data suggests that PWT and DYT share some pathophysiological mechanisms.

a.latorre@ucl.ac.uk
119  NeuroToolkit CSF biomarkers track the progression of Alzheimer’s disease at very early stages
Authors: Molinuevo JL , Salvadó G , Kollmorgen G , Milà-Alomà M , Blennow K , Zetterberg H , Farrar G , Suarez-Calvet M , Gispert JD
Published: May 2022

Introduction

NeuroToolkit is a set of cerebrospinal fluid (CSF) biomarkers developed to identify Alzheimer’s disease co-pathologies, identify and characterize disease progression and treatment response. We assess the association between NeuroToolkit biomarkers and cerebral amyloid deposition in the ALFA+ cohort [1].

Methods

326 cognitively unimpaired individuals from the ALFA+ cohort [1] underwent a lumbar puncture and amyloid [18F]flutemetamol PET imaging. Biomarkers in NeuroToolkit (Figure 1) were determined using prototype Roche Elecsys® assays. CSF pTau levels were measured using the Elecsys® CSF assay. We cal- culated cross-correlation values between NeuroToolkit biomarkers and Centiloids. Voxel-wise associations between NeuroToolkit biomarkers and [18F]flutemetamol images were sought, accounting for the effect of various demographics. Additional analyses were performed after correcting also for the Aα42/40 ratio or Centiloid values.

Results

Figure 1. Shows associations between NeuroToolkit biomarkers and Centiloids. NeuroToolkit bio- markers were significantly associated with cerebral amyloid deposition measured by [18F]flutemetamol PET (Figure 2). Correcting for global amyloid deposition, higher levels CSF YKL-40, an astroglial activity marker, were associated to increased cerebral amyloid deposition in the inferior and lateral temporal lobe, in parietal and orbitofrontal areas, and the caudate heads (Figure 3).

Conclusions

Results of NeuroToolkit biomarkers support early involvement of the astroglial response to cerebral amyloid deposition.

Disclosure

This study was conducted through a collaboration with Roche Diagnostics International. These data will be presented at Advances in Alzheimer’s and Parkinson’s Therapies. Ref: Molinuevo. TRCI 2 (2016) 82–92

gwendlyn.kollmorgen@roche.com