bluuebunny/crossref_metadata_2025 huggingface dataset:
Quality framework for remote antenatal care: qualitative study with women, healthcare professionals and system-level stakeholders
Authors: Hinton Lisa , Dakin Francesca H , Kuberska Karolina , Boydell Nicola , Willars Janet , Draycott Tim , Winter Cathy , McManus Richard J , Chappell Lucy C , Chakrabarti Sanhita , Howland Elizabeth , George Jenny , Leach Brandi , Dixon-Woods Mary
Published: May 2022

Background

High-quality antenatal care is important for ensuring optimal birth outcomes and reducing risks of maternal and fetal mortality and morbidity. The COVID-19 pandemic disrupted the usual provision of antenatal care, with much care shifting to remote forms of provision. We aimed to characterise what quality would look like for remote antenatal care from the perspectives of those who use, provide and organise it.

Methods

This UK-wide study involved interviews and an online survey inviting free-text responses with: those who were or had been pregnant since March 2020; maternity professionals and managers of maternity services and system-level stakeholders. Recruitment used network-based approaches, professional and community networks and purposively selected hospitals. Analysis of interview transcripts was based on the constant comparative method. Free-text survey responses were analysed using a coding framework developed by researchers.

Findings

Participants included 106 pregnant women and 105 healthcare professionals and managers/stakeholders. Analysis enabled generation of a framework of the domains of quality that appear to be most relevant to stakeholders in remote antenatal care: efficiency and timeliness; effectiveness; safety; accessibility; equity and inclusion; person-centredness and choice and continuity. Participants reported that remote care was not straightforwardly positive or negative across these domains. Care that was more transactional in nature was identified as more suitable for remote modalities, but remote care was also seen as having potential to undermine important aspects of trusting relationships and continuity, to amplify or create new forms of structural inequality and to create possible risks to safety.

Conclusions

This study offers a provisional framework that can help in structuring thinking, policy and practice. By outlining the range of domains relevant to remote antenatal care, this framework is likely to be of value in guiding policy, practice and research.
Documenting the indication for antimicrobial prescribing: a scoping review
Authors: Saini Sharon , Leung Valerie , Si Elizabeth , Ho Certina , Cheung Anne , Dalton Dan , Daneman Nick , Grindrod Kelly , Ha Rita , McIsaac Warren , Oberai Anjali , Schwartz Kevin , Shiamptanis Anastasia , Langford Bradley J
Published: May 2022

Background

Documenting an indication when prescribing antimicrobials is considered best practice; however, a better understanding of the evidence is needed to support broader implementation of this practice.

Objectives

We performed a scoping review to evaluate antimicrobial indication documentation as it pertains to its implementation, prevalence, accuracy and impact on clinical and utilisation outcomes in all patient populations.

Eligibility criteria

Published and unpublished literature evaluating the documentation of an indication for antimicrobial prescribing.

Sources of evidence

A search was conducted in MEDLINE, Embase, CINAHL and International Pharmaceutical Abstracts in addition to a review of the grey literature.

Charting and analysis

Screening and extraction was performed by two independent reviewers. Studies were categorised inductively and results were presented descriptively.

Results

We identified 123 peer-reviewed articles and grey literature documents for inclusion. Most studies took place in a hospital setting (109, 89%). The median prevalence of antimicrobial indication documentation was 75% (range 4%–100%). Studies evaluating the impact of indication documentation on prescribing and patient outcomes most commonly examined appropriateness and identified a benefit to prescribing or patient outcomes in 17 of 19 studies. Qualitative studies evaluating healthcare worker perspectives (n=10) noted the common barriers and facilitators to this practice.

Conclusion

There is growing interest in the importance of documenting an indication when prescribing antimicrobials. While antimicrobial indication documentation is not uniformly implemented, several studies have shown that multipronged approaches can be used to improve this practice. Emerging evidence demonstrates that antimicrobial indication documentation is associated with improved prescribing and patient outcomes both in community and hospital settings. But setting-specific and larger trials are needed to provide a more robust evidence base for this practice.
Persisting breathlessness and activities reduced or ceased: a population study in older men
Authors: Kochovska Slavica , Currow David , Chang Sungwon , Johnson Miriam , Ferreira Diana , Morgan Deidre , Olsson Max , Ekström Magnus
Published: May 2022

Introduction

Breathlessness is debilitating and increases in prevalence with age, with people progressively reducing their everyday activities to ‘self-manage’ it. This study aimed to evaluate the impact of breathlessness on function in terms of activities that have been reduced or ceased (‘compromised’) in older men.

Methods

A cross-sectional postal survey of Swedish 73-year-old man in the VAScular and Chronic Obstructive Lung disease study self-reporting on demographics, breathlessness (modified Medical Research Council (mMRC) scale, Dyspnoea-12, Multidimensional Dyspnea Scale) and its duration, anxiety/depression (Hospital Anxiety and Depression Scale), performance status (WHO Performance Status), everyday activities reduced/ceased and exertion.

Results

148/828 (17.9%) respondents reported breathlessness (mMRC>2), of whom 51.9% had reduced/ceased activities compared with 9.6% who did not. Physical activity was the most common activity reduced/ceased (48.0%) followed by sexual activity (41.2%) and social activities (37.8%). Of 16.0% of respondents with mMRC 3–4 talking on the phone was affected compared with only 2.9% of respondents with mMRC 2. Worsening breathlessness was associated with increasingly sedentary lifestyles and more limited function, those reporting reduced/ceased activities had an associated increase in reporting anxiety and depression. In adjusted analyses, breathlessness was associated with increased likelihood of activities being ceased overall as well as physical and sexual activities being affected separately.

Conclusion

Worsening breathlessness was associated with decreasing levels of self-reported physical activity, sexual activity and function. Overall, the study showed that people with persisting breathlessness modify their lifestyle to avoid it by reducing or ceasing a range of activities, seeking to minimise their exposure to the symptom.
Patients’ and their caregivers’ experiences with regular, low-dose, sustained-release morphine for chronic breathlessness associated with COPD: a qualitative study
Authors: Ferreira Diana , Kochovska Slavica , Honson Aaron , Phillips Jane , Currow David
Published: May 2022

Introduction

Regular, low-dose, sustained-release morphine is effective in reducing chronic breathlessness in people with advanced disease, particularly in patients with chronic obstructive pulmonary disease (COPD). Despite experiencing a reduction in breathlessness, some patients choose not to continue long-term treatment.

Aim

This study aimed to explore patients’ and caregivers’ experiences with regular, low-dose, sustained-release morphine for chronic breathlessness associated with COPD.

Methods

A qualitative study embedded in a randomised controlled trial (RCT) of regular low-dose, sustained-release morphine for chronic breathlessness for people with COPD and modified Medical Research Council breathlessness scale 3–4. After completing the RCT or withdrawing, patients and their caregivers were invited to participate in interviews in their homes focused on their experiences with the trial medication while still blinded to the arm to which they had been allocated. Data analysis used a constant comparative method informed by the principles of grounded theory.

Results

Thirteen patients and nine caregivers participated. Four themes were identified: (1) Receptivity and knowledge; (2) Function as a priority; (3) Harmful and helpful side effects; and (4) Therapy-centred aspects. The concept of ‘net effect’ emerged from the interplay between themes, subthemes and the decision to continue taking sustained-release morphine during the trial and after trial completion.

Conclusion

Clinicians’ support and preconceived ideas about morphine influence the decision to commence sustained-release morphine. The hope for functional improvement is the great driver influencing positively the decision to take sustained-release morphine in the long term. The degree of symptom reduction, improved function, side-effects’ severity and caregivers’ availability creates a net effect driving patients’ decisions to continue or discontinue the medication.
Assessment of 24-hour physical behaviour in children and adolescents via wearables: a systematic review of free-living validation studies
Authors: Giurgiu Marco , Kolb Simon , Nigg Carina , Burchartz Alexander , Timm Irina , Becker Marlissa , Rulf Ellen , Doster Ann-Kathrin , Koch Elena , Bussmann Johannes B J , Nigg Claudio , Ebner-Priemer Ulrich W , Woll Alexander
Published: May 2022

Objectives

Studies that assess all three dimensions of the integrative 24-hour physical behaviour (PB) construct, namely, intensity, posture/activity type and biological state, are on the rise. However, reviews on validation studies that cover intensity, posture/activity type and biological state assessed via wearables are missing.

Design

Systematic review. The risk of bias was evaluated by using the QUADAS-2 tool with nine signalling questions separated into four domains (ie, patient selection/study design, index measure, criterion measure, flow and time).

Data sources

Peer-reviewed validation studies from electronic databases as well as backward and forward citation searches (1970–July 2021).

Eligibility criteria for selecting studies

Wearable validation studies with children and adolescents (age <18 years). Required indicators: (1) study protocol must include real-life conditions; (2) validated device outcome must belong to one dimension of the 24-hour PB construct; (3) the study protocol must include a criterion measure; (4) study results must be published in peer-reviewed English language journals.

Results

Out of 13 285 unique search results, 76 articles with 51 different wearables were included and reviewed. Most studies (68.4%) validated an intensity measure outcome such as energy expenditure, but only 15.9% of studies validated biological state outcomes, while 15.8% of studies validated posture/activity type outcomes. We identified six wearables that had been used to validate outcomes from two different dimensions and only two wearables (ie, ActiGraph GT1M and ActiGraph GT3X+) that validated outcomes from all three dimensions. The percentage of studies meeting a given quality criterion ranged from 44.7% to 92.1%. Only 18 studies were classified as ‘low risk’ or ‘some concerns’.

Validation studies on biological state and posture/activity outcomes are rare in children and adolescents. Most studies did not meet published quality principles. Standardised protocols embedded in a validation framework are needed.

PROSPERO registration number

CRD42021230894.
Mindfulness-based supportive therapy on reducing suffering in patients with advanced cancer: randomised controlled trial
Authors: Tan Seng Beng , Chee Chung Huey , Ngai Chin Fei , Hii Siew Lin , Tan Yi Wen , Ng Chong Guan , Capelle David Paul , Zainuddin Sheriza Izwa , Loh Ee Chin , Lam Chee Loong , Chai Chee Shee , Ng Diana Leh Ching
Published: May 2022

Objectives

Suffering is common among patients with advanced cancer. The practice of mindfulness during patient care can potentially reduce suffering. We aimed to examine the efficacy of mindfulness-based supportive therapy (MBST) on reducing suffering in patients with advanced cancer.

Methods

We conducted a parallel-group, single-blinded, randomised controlled trial at the University of Malaya Medical Centre, Malaysia. Seventy-three patients with advanced cancer with an overall suffering score ≥4/10 based on the Suffering Pictogram were recruited and randomly assigned into either the MBST group (n=34) or the control group (n=39).

Results

There was a statistically significant reduction in the overall suffering score in the MBST group compared with the control group (U=432.5, median1=−2.0, median2=−1.0, z=−2.645, p=0.008). There was also significant improvement in the total Hospital Anxiety and Depression Scale score (U=483.5, median1=−4.0, median2=−3.0, z=−1.994, p=0.046), and the total Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being score (U=252.0, median1=+14.5, median2=+5.0, z=−4.549, p=0.000) in the MBST group compared with the control group.

Conclusions

The results provided evidence that the practice of MBST during patient care could promote positive psychosocial outcomes.
Clinical nurse specialists and survival in patients with cancer: the UK National Cancer Experience Survey
Authors: Alessy Saleh A , Davies Elizabeth , Rawlinson Janette , Baker Matthew , Lüchtenborg Margreet
Published: May 2022

Objective

To examine whether having a better care experience with a clinical nurse specialist (CNS) is associated with better overall survival of patients with cancer in England.

Methods

We identified 99 371 patients with colorectal, lung, breast and prostate cancer who reported their care experience with CNS from the National Cancer Patient Experience Survey (2010–2014) and English cancer registration linked dataset. We categorised patients’ experiences into three groups (excellent, non-excellent and no CNS name was given), across three aspects of CNS care: the ease of contacting their CNS, feeling that a CNS had listened to them and the degree to which explanations given by a CNS were understandable. We used univariable and multivariable Cox proportional hazards regression analyses to estimate HRs with 95% CIs by patient experience for each cancer adjusting for patients’ sociodemographic and disease stage at diagnosis.

Results

Among the three compared groups, patients who reported not being given a CNS name had the lowest survival. In the adjusted Cox regression analysis, the results show that among those who reported not being given a CNS name, the highest risk of death was in those with colorectal, breast and prostate cancers only (colorectal HR: 1.40; 95% CI: 1.32 to 1.84; breast HR: 1.34; 95% CI: 1.25 to 1.44; prostate HR: 1.09; 95% CI: 0.99 to 1.13). However, this association seemed reversed among patients with lung cancer, although attenuated when accounting for potential confounders.

Conclusion

These findings provide new evidence of the vital contribution CNS may make to cancer survival and suggest CNS input and support should be available to all patients after the diagnosis.
Missing data in palliative care research: estimands and estimators
Authors: Roydhouse Jessica , Floden Lysbeth , Braat Sabine , Grobler Anneke , Kochovska Slavica , Currow David C , Bell Melanie L
Published: May 2022

There are several methodological challenges when conducting randomised controlled trials in palliative care. These include worsening function and high mortality, leading to treatment discontinuation, some of which will be unrelated to the intervention being evaluated.

Recently, a new framework for handling postrandomisation events, such as attrition, has been released. This framework aims to align trial objectives, design, conduct and analysis by clarifying what and how to estimate treatment effects in the presence of data affected by postrandomisation events.

The purpose of this paper is to introduce palliative care researchers to this framework and how it can guide trial design, and efficacy and safety analysis in a palliative care context where individual withdrawal from the trial is common.

In this paper, we describe the estimand framework and the background for it. We also consider postrandomisation events that are frequently encountered in palliative care trials and how these might affect objectives of interest. We then construct efficacy and safety estimands for a trial in palliative care. Better trial design and alignment of objectives with analysis can improve our understanding of what treatments do and do not work in palliative care.
Allogeneic haematopoietic stem cell transplantation and patient falls: impact of lower extremity muscle strength
Authors: Kondo Shin , Inoue Tatsuro , Saito Takashi , Kawamura Yuka , Katayama Ayane , Nakamura Masafumi , Sumitani Ryohei , Takahashi Mamiko , Oura Masahiro , Sogabe Kimiko , Harada Takeshi , Fujii Shiro , Nakamura Shingen , Miki Hirokazu , Kagawa Kumiko , Sato Nori , Ono Rei , Abe Masahiro , Katoh Shinsuke
Published: May 2022

Objectives

Patients undergoing allogeneic haematopoietic stem cell transplantation (allo-HSCT) have a higher risk of falls than those receiving other therapies for haematological disorders. This study aimed to investigate the impact of pretransplant lower extremity muscle strength (LEMS) on post-transplant falls.

Methods

In this retrospective cohort study, patients aged ≥18 years who underwent allo-HSCT were included. All data were extracted from medical records. LEMS was defined as the knee extension force measured by a handheld dynamometer divided by the patient’s weight. The receiver operating characteristic (ROC) curve was used to calculate the optimal LEMS cut-off value for prediction of falls. Patients were categorised into low and normal LEMS groups based on the cut-off value. The impact of pretransplant LEMS on post-transplant falls was analysed using a Cox proportional hazards model.

Results

In total, 101 patients were analysed. During the observation period, falls occurred in 32 patients (31.7%). The ROC curve analysis results showed that the optimal LEMS cut-off value for prediction of falls was 45.4% per body weight. In multivariate analysis, pretransplant low LEMS was a significant predictor of falls in model 1 with patient characteristics as a confounding factor and model 2 with medications-inducing falls as a confounding factor, respectively (model 1: HR 3.23, 95% CI 1.37 to 7.64; model 2: HR 2.82, 95% CI 1.20 to 6.59).

Conclusions

Pretransplant LEMS was a significant predictor of post-transplant falls. The results of this study may help to prevent falls in patients undergoing allo-HSCT.
Development of a measure of clinicians’ self-efficacy for medical communication (SEMC)
Authors: Feldman David B. , O'Rourke Mark A. , Corn Benjamin W. , Hudson Matthew F. , Patel Naimik , Agarwal Rajiv , Fraser Valerie L. , Deininger Heidi , Fowler Lauren A. , Bakitas Marie A. , Krouse Robert A. , Subbiah Ishwaria M.
Published: May 2022

Objectives

Studies of clinician–patient communication have used varied, ad hoc measures for communication efficacy. We developed and validated the Self-Efficacy for Medical Communication (SEMC) scale as a standard, quantitative measure of clinician-reported skills in communicating difficult news.

Methods

Using evidence-based scale development guidelines, we created two 16-item forms of the SEMC, one assessing communication with patients and one assessing communication with families. Clinicians providing oncological care in four organisations were invited to participate and provided consent. Participant demographics, responses to the SEMC items and responses to convergent and discriminant measures (those expected to relate strongly and weakly to the SEMC) were collected online. We performed analyses to determine the convergent and discriminant validity of the SEMC as well as its reliability and factor structure.

Results

Overall, 221 oncology clinicians (including physicians, residents, fellows, medical students, nurses, nurse practitioners and physician assistants) participated. The patient and family forms both demonstrated high internal consistency reliability (alpha=0.94 and 0.96, respectively) and were strongly correlated with one another (r=0.95, p<0.001). Exploratory factor analysis demonstrated that the SEMC measures a unitary construct (eigenvalue=9.0), and its higher mean correlation with convergent (r=0.46) than discriminant (r=0.22) measures further supported its validity.

Conclusions

Our findings support the SEMC’s validity and reliability as a measure of clinician-rated communication skills regarding conducting difficult conversations with patients and families. It provides a useful standard tool for future research in oncology provider–patient serious illness communication.
Hot flash clinical trial baseline measurements: how long is needed?
Authors: Childs Daniel S , Novotny Paul J , Marell Paulina S , Ruddy Kathryn J , Loprinzi Charles L
Published: May 2022

Objectives

Classically, hot flash studies included a baseline period of 1 week or longer. The objective of this study was to compare the accuracy of a 1-day baseline diary to a traditional 1-week diary.

Methods

Raw data from 5 pilot studies and 15 phase III randomised controlled trials (RCTs), all of which used a 1-week baseline period, were obtained. Descriptive statistics were used to describe day-by-day variations in hot flash frequencies and scores, during the baseline week. Additional analyses evaluated whether the conclusions from any of the individual pilot studies would have been changed if only a 1-day baseline period had been used. For the RCTs, p values were recalculated using mixed models, adjusting for the baseline value by including it as a covariate.

Results

A total of 2573 participants were included. On average, participants had 8.5 hot flashes per day on day 1. Mean hot flash frequencies and scores on subsequent days (days 2–7) were within 6% of day 1 values. When comparing a 1-day to a 1-week baseline period, there was an absolute difference of only 0.29 hot flashes per day (SD 2.25). Reanalysis for each pilot study revealed that no individual study conclusions would have been altered by a shorter baseline. For the RCTs, a shorter baseline period changed the results of only 1 of 24 comparisons from statistically significant to not significant, or vice versa.

Conclusions

A 1-day hot flash diary appears to accurately reflect the true frequency and severity of baseline symptoms in appropriately sized cohorts.
COVID-19 vaccine hesitancy and related factors among primary healthcare workers in a district of Istanbul: a cross-sectional study from Turkey
Authors: İkiışık Hatice , Sezerol Mehmet Akif , Taşçı Yusuf , Maral Işıl
Published: May 2022

Objectives

This study aimed to determine the COVID-19 risk perceptions, vaccination intentions and predictive factors of family physicians and family healthcare staff working in primary care in Üsküdar.

Design

A cross-sectional study was performed using an online questionnaire to determine the demographic and general characteristics of the participants and their willingness to be vaccinated.

Setting

An online questionnaire was applied to family physicians and family health workers working in primary care family health centres in Üsküdar between 25 and 29 December 2020. Multivariate analysis was performed to identify independent predictors of the willingness of individuals to be vaccinated.

Participants

Out of 323 health workers working in 44 family health centres in the district, a total of 276 health workers were reached, including 126 physicians (n=158, 79.7%) and 150 midwives/nurses (n=165, 90.9%) (response rate 85.4%).

Results

50.4% (n=139) of the healthcare workers were willing to have the COVID-19 vaccine, 29% (n=80) were undecided and 20.7% (n=57) refused the vaccine. The rate of acceptance to be vaccinated was higher in physicians, in men and in those who had not received a seasonal influenza vaccination regularly each year.

Conclusions

Half of the primary healthcare workers, one of the high-risk groups in the pandemic, were hesitant or refused to be vaccinated for COVID-19. Knowing the factors affecting the vaccine acceptance rates of healthcare professionals can be considered one of the most strategic moves in reaching the target of high community vaccination rates. For evidence-based planning in vaccination studies, there is a need to investigate the reasons for COVID-19 vaccine acceptance by healthcare workers at all levels.
Abnormal neural oscillations in clinical high risk for psychosis: a magnetoencephalography method study
Authors: Hu Yegang , Wu Jun , Cao YuJiao , Tang XiaoChen , Wu GuiSen , Guo Qian , Xu LiHua , Qian ZhenYing , Wei YanYan , Tang YingYing , Li ChunBo , Zhang Tianhong , Wang Jijun
Published: May 2022

Background

Neural oscillations directly reflect the rhythmic changes of brain activities during the resting state or while performing specific tasks. Abnormal neural oscillations have been discovered in patients with schizophrenia. However, there is limited evidence available on abnormal spontaneous neural oscillations in clinical high risk for psychosis (CHR-P). The brain signals recorded by the magnetoencephalography (MEG) technique are not to be disrupted by the skull and scalp.

Methods

In this study, we applied the MEG technique to record the resting-state neural activities in CHR-P. This was followed by a detailed MEG analysis method including three steps: (1) preprocessing, which was band-pass filtering based on the 0.5–60 Hz frequency range, removal of 50 Hz power frequency interference, and removal of electrocardiography (ECG) and electrooculography (EOG) artefacts by independent component analysis; (2) time-frequency analysis, a multitaper time-frequency transformation based on the Hanning window, and (3) source localisation, an exact low-resolution brain electromagnetic tomography. The method was verified by comparing a participant with CHR-P with a healthy control during the MEG recordings with an eyes-closed resting state.

Results

Experimental results show that the neural oscillations in CHR-P were significantly abnormal in the theta frequency band (4–7 Hz) and the delta frequency band (1–3 Hz). Also, relevant brain regions were located in the left occipital lobe and left temporo-occipital junction for the theta band and in the right dorsolateral prefrontal lobe and near orbitofrontal gyrus for the delta band.

Conclusions

Abnormal neural oscillations based on specific frequency bands and corresponding brain sources may become biomarkers for high-risk groups. Further work will validate these characteristics in CHR-P cohorts.
Endoscopic pyloromyotomy for the treatment of severe and refractory gastroparesis: a pilot, randomised, sham-controlled trial
Authors: Martinek Jan , Hustak Rastislav , Mares Jan , Vackova Zuzana , Spicak Julius , Kieslichova Eva , Buncova Marie , Pohl Daniel , Amin Sunil , Tack Jan
Published: May 2022

Objective

Endoscopic pyloromyotomy (G-POEM) is a minimally invasive treatment option with promising uncontrolled outcome results in patients with gastroparesis.

Design

In this prospective randomised trial, we compared G-POEM with a sham procedure in patients with severe gastroparesis. The primary outcome was the proportion of patients with treatment success (defined as a decrease in the Gastroparesis Cardinal Symptom Index (GCSI) by at least 50%) at 6 months. Patients randomised to the sham group with persistent symptoms were offered cross-over G-POEM.

Results

The enrolment was stopped after the interim analysis by the Data and Safety Monitoring Board prior to reaching the planned sample of 86 patients. A total of 41 patients (17 diabetic, 13 postsurgical, 11 idiopathic; 46% male) were randomised (21 G-POEM, 20-sham). Treatment success rate was 71% (95% CI 50 to 86) after G-POEM versus 22% (8–47) after sham (p=0.005). Treatment success in patients with diabetic, postsurgical and idiopathic gastroparesis was 89% (95% CI 56 to 98), 50% (18–82) and 67% (30–90) after G-POEM; the corresponding rates in the sham group were 17% (3–57), 29% (7–67) and 20% (3–67).

Median gastric retention at 4 hours decreased from 22% (95% CI 17 to 31) to 12% (5–22) after G-POEM and did not change after sham: 26% (18–39) versus 24% (11–35). Twelve patients crossed over to G-POEM with 9 of them (75%) achieving treatment success.

Conclusion

In severe gastroparesis, G-POEM is superior to a sham procedure for improving both symptoms and gastric emptying 6 months after the procedure. These results are not entirely conclusive in patients with idiopathic and postsurgical aetiologies.

Trial registration number

NCT03356067; ClinicalTrials.gov.
Clinical relevance of biomarkers in cholangiocarcinoma: critical revision and future directions
Authors: Macias Rocio I R , Cardinale Vincenzo , Kendall Timothy J , Avila Matias A , Guido Maria , Coulouarn Cedric , Braconi Chiara , Frampton Adam E , Bridgewater John , Overi Diletta , Pereira Stephen P , Rengo Marco , Kather Jakob N , Lamarca Angela , Pedica Federica , Forner Alejandro , Valle Juan W , Gaudio Eugenio , Alvaro Domenico , Banales Jesus M , Carpino Guido
Published: May 2022

Cholangiocarcinoma (CCA) is a malignant tumour arising from the biliary system. In Europe, this tumour frequently presents as a sporadic cancer in patients without defined risk factors and is usually diagnosed at advanced stages with a consequent poor prognosis. Therefore, the identification of biomarkers represents an utmost need for patients with CCA. Numerous studies proposed a wide spectrum of biomarkers at tissue and molecular levels. With the present paper, a multidisciplinary group of experts within the European Network for the Study of Cholangiocarcinoma discusses the clinical role of tissue biomarkers and provides a selection based on their current relevance and potential applications in the framework of CCA. Recent advances are proposed by dividing biomarkers based on their potential role in diagnosis, prognosis and therapy response. Limitations of current biomarkers are also identified, together with specific promising areas (ie, artificial intelligence, patient-derived organoids, targeted therapy) where research should be focused to develop future biomarkers.
Association between exercise habit changes and mortality following a cardiovascular event
Authors: Kang Dong-Seon , Sung Jung-Hoon , Kim Daehoon , Jin Moo-Nyun , Jang Eunsun , Yu Hee Tae , Kim Tae-Hoon , Pak Hui-Nam , Lee Moon-Hyoung , Lip Gregory , Yang Pil-Sung , Joung Boyoung
Published: May 2022

Objective

To investigate the associations between exercise habit changes following an incident cardiovascular event and mortality in older adults.

Methods

We analysed the relationship between exercise habit change and all-cause, cardiovascular and non-cardiovascular deaths in adults aged ≥60 years between 2003 and 2012 who underwent two consecutive health examinations within 2 years before and after diagnosis of cardiovascular disease (CVD). They were categorised into four groups according to exercise habit changes: persistent non-exercisers, exercise dropouts, new exercisers and exercise maintainers. Differences in baseline characteristics were adjusted using inverse probability of treatment weighting.

Results

Of 6076 participants, the median age was 72 (IQR 69–76) years and men accounted for 50.6%. Compared with persistent non-exercisers (incidence rate (IR) 4.8 per 100 person-years), new exercisers (IR 3.5, HR 0.73, 95% CI 0.58 to 0.91) and exercise maintainers (IR 2.9, HR 0.53, 95% CI 0.38 to 0.73) were associated with reduced risk of all-cause death. The rate of non-cardiovascular death was significantly lower in new exercisers (IR 2.3, HR 0.73, 95% CI 0.56 to 0.95) and exercise maintainers (IR 2.3, HR 0.61, 95% CI 0.42 to 0.90) than in persistent non-exercisers (IR 3.2). Also, trends towards reduced cardiovascular death in new exercisers and exercise maintainers were observed (p value for trend <0.001).

Conclusions

More virtuous exercise trajectories in older adults with CVD are associated with lower mortality rates. Our results support public health recommendations for older adults with CVD to perform physical activity.
A Qualitative study on diverse perspectives and identities of firearm owners
Authors: Thomas Arielle C. , Siry-Bove Bonnie J. , Barnard Leslie M. , Rooney Lauren , McCarthy Megan , Mustafa Ayah , Rowhani-Rahbar Ali , Rivara Frederick P. , Betz Marian E. , Knoepke Christopher
Published: May 2022

Objective

Research surrounding firearm ownership is often contextualised within the perspectives of older white men. We expand this description using the perceptions of a diverse group of firearm-owning stakeholders.

Methods

We conducted semistructured interviews from October 2020 to May 2021 with Colorado/Washington State stakeholders representing (1) firearm ranges/retailers; (2) law enforcement agencies or (3) relevant state/national firearm organisations. Data were analysed using standard qualitative techniques and included 25 participants, representing varied sociocultural groups including racial and ethnic minorities, political minorities and sexual minorities.

Results

Participants for this analysis were of different self-identified sociocultural groups including racial and ethnic minorities (African American, Hispanic and Asian), political minorities (liberal) and sexual minorities, defined as Lesbian, Gay, Bisexual, and Transgender (LGBT). Perspectives on firearm ownership included an idea of gun culture as a component of (1) personal identity, (2) an expression of full citizenship and (3) necessary for self-protection. A strong subtheme was the intersection of minority group and firearm owner identities, creating a need for divergent social communities because of ideas on traditional gun culture. These communities are a safe place for individuals belonging to minority groups to escape negative external and internal group associations with firearms.

Conclusion

Perspectives on firearms and firearm ownership in the secondary analysis were heterogeneous and related to personal experiences, external and internal group pressures that influence individual behaviour. Understanding the breadth of perspectives on firearm ownership is imperative to engaging individuals for risk reduction. This study adds to the literature by expanding an understanding of the motivation for firearm ownership among diverse communities.
Treatment gaps, 1-year readmission and mortality following myocardial infarction by diabetes status, sex and socioeconomic disadvantage
Authors: Morton Jedidiah I , Ilomäki Jenni , Wood Stephen J , Bell J Simon , Huynh Quan , Magliano Dianna J , Shaw Jonathan E
Published: May 2022

Aims

We evaluated variation in treatment for, and outcomes following, myocardial infarction (MI) by diabetes status, sex and socioeconomic disadvantage.

Methods

We included all people aged ≥30 years who were discharged alive from hospital following MI between 1 July 2012 and 30 June 2017 in Victoria, Australia (n=43 272). We assessed receipt of inpatient procedures and discharge dispensing of cardioprotective medications for each admission, as well as 1-year all-cause, cardiovascular, and MI readmission rates and 1-year all-cause mortality.

Results

Risk of all-cause (HR: 1.22 (1.19–1.26)), cardiovascular (1.29 (1.25–1.34)), MI (1.52 (1.43–1.62)) and heart failure readmission (1.62 (1.50–1.75)) and mortality (1.18 (1.11–1.26)) were higher in people with diabetes. Males and people in more disadvantaged areas were at increased risk of readmission and mortality following MI. People with diabetes (vs without) were more likely to receive coronary artery bypass grafting (CABG) but less likely to receive percutaneous coronary intervention (PCI) during, or within 30 days of, their index admission. Females were less likely to receive either (eg, 87% of males with a STEMI received PCI or CABG vs 70% of females), and people in more disadvantaged areas were less likely to receive PCI. People with diabetes, males and people in more disadvantaged areas were more likely to be dispensed cardioprotective medications at or within 90 days of discharge.

Conclusions

Following an MI, people with diabetes and males had poorer outcomes but received more intensive cardiovascular treatments. However, socioeconomic disadvantage was associated with both less intensive inpatient treatment and poorer outcomes.
Monitoring sociodemographic inequality in COVID-19 vaccination uptake in England: a national linked data study
Authors: Dolby Ted , Finning Katie , Baker Allan , Fowler-Dowd Leigh , Khunti Kamlesh , Razieh Cameron , Yates Thomas , Nafilyan Vahe
Published: May 2022

Background

The UK began an ambitious COVID-19 vaccination programme on 8 December 2020. This study describes variation in vaccination uptake by sociodemographic characteristics between December 2020 and August 2021.

Methods

Using population-level administrative records linked to the 2011 Census, we estimated monthly first dose vaccination rates by age group and sociodemographic characteristics among adults aged 18 years or over in England. We also present a tool to display the results interactively.

Results

Our sample included 35 223 466 adults. A lower percentage of males than females were vaccinated in the young and middle age groups (18–59 years) but not in the older age groups. Vaccination rates were highest among individuals of White British and Indian ethnic backgrounds and lowest among Black Africans (aged ≥80 years) and Black Caribbeans (18–79 years). Differences by ethnic group emerged as soon as vaccination roll-out commenced and widened over time. Vaccination rates were also lower among individuals who identified as Muslim, lived in more deprived areas, reported having a disability, did not speak English as their main language, lived in rented housing, belonged to a lower socioeconomic group, and had fewer qualifications.

Conclusion

We found inequalities in COVID-19 vaccination uptake rates by sex, ethnicity, religion, area deprivation, disability status, English language proficiency, socioeconomic position and educational attainment, but some of these differences varied by age group. Research is urgently needed to understand why these inequalities exist and how they can be addressed.
Camrelizumab plus famitinib for advanced or metastatic urothelial carcinoma after platinum-based therapy: data from a multicohort phase 2 study
Authors: Qu Yuan-Yuan , Sun Zhongquan , Han Weiqing , Zou Qing , Xing Nianzeng , Luo Hong , Zhang Xuepei , He Chaohong , Bian Xiao-Jie , Cai Jinling , Chen Chunxia , Wang Quanren , Ye Ding-Wei
Published: May 2022

Background

Dual blockade of immune checkpoint and angiogenesis is an effective strategy for multiple cancers. Camrelizumab is a monoclonal antibody against PD-1, and famitinib is a multitargeted receptor tyrosine kinase inhibitor with antiangiogenesis and antiproliferation activities against tumor cells. We conducted an open-label, multicenter phase 2 basket study of camrelizumab and famitinib in eight cohorts of genitourinary or gynecological cancers. Here, findings in cohort of advanced or metastatic urothelial carcinoma with platinum-progressive disease (cohort 2) are presented.

Methods

Patients who had progressed after platinum-based chemotherapy for advanced or metastatic disease or had progressed within 12 months after completion of platinum-based (neo)adjuvant therapy were given camrelizumab (200 mg intravenously every 3 weeks) plus famitinib (20 mg orally once daily). Primary endpoint was objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1.

Results

Totally, 36 patients were recruited. With a median duration from enrollment to data cut-off of 11.9 months (range 6.1–28.5), ORR was 30.6% (95% CI 16.3% to 48.1%). Median duration of response (DoR) was 6.3 months (95% CI 2.1 to not reached). Median progression-free survival (PFS) was 4.1 months (95% CI 2.2 to 8.2), and median overall survival (OS) was 12.9 months (95% CI 8.8 to not reached). Patients with bladder cancer (n=18) had numerically better outcomes, with an ORR of 38.9% (95% CI 17.3% to 64.3%) and a median PFS of 8.3 months (95% CI 4.1 to not reached). Median DoR and OS in this subpopulation had not been reached with lower limit of 95% CI of 4.2 months for DoR and 11.3 months for OS, respectively. Of 36 patients, 22 (61.1%) had grade 3 or 4 treatment-related adverse events, mainly decreased platelet count and hypertension.

Conclusions

Camrelizumab plus famitinib showed potent antitumor activity in advanced or metastatic urothelial carcinoma patients after platinum-based chemotherapy. Patients with bladder cancer seemed to have better response to this combination.

Trial registration number

NCT03827837.
A2Badenosine receptor antagonists rescue lymphocyte activity in adenosine-producing patient-derived cancer models
Authors: Tay Apple Hui Min , Prieto-Díaz Rubén , Neo Shiyong , Tong Le , Chen Xinsong , Carannante Valentina , Önfelt Björn , Hartman Johan , Haglund Felix , Majellaro Maria , Azuaje Jhonny , Garcia-Mera Xerardo , Brea Jose M , Loza Maria I , Jespers Willem , Gutierrez-de-Teran Hugo , Sotelo Eddy , Lundqvist Andreas
Published: May 2022

Background

Adenosine is a metabolite that suppresses antitumor immune response of T and NK cells via extracellular binding to the two subtypes of adenosine-2 receptors, A2ARs. While blockade of the A2AARs subtype effectively rescues lymphocyte activity, with four A2AAR antagonists currently in anticancer clinical trials, less is known for the therapeutic potential of the other A2BAR blockade within cancer immunotherapy. Recent studies suggest the formation of A2AAR/A2BAR dimers in tissues that coexpress the two receptor subtypes, where the A2BAR plays a dominant role, suggesting it as a promising target for cancer immunotherapy.

Methods

We report the synthesis and functional evaluation of five potent A2BAR antagonists and a dual A2AAR/A2BAR antagonist. The compounds were designed using previous pharmacological data assisted by modeling studies. Synthesis was developed using multicomponent approaches. Flow cytometry was used to evaluate the phenotype of T and NK cells on A2BAR antagonist treatment. Functional activity of T and NK cells was tested in patient-derived tumor spheroid models.

Results

We provide data for six novel small molecules: five A2BAR selective antagonists and a dual A2AAR/A2BAR antagonist. The growth of patient-derived breast cancer spheroids is prevented when treated with A2BAR antagonists. To elucidate if this depends on increased lymphocyte activity, immune cells proliferation, and cytokine production, lymphocyte infiltration was evaluated and compared with the potent A2AAR antagonist AZD-4635. We find that A2BAR antagonists rescue T and NK cell proliferation, IFNγ and perforin production, and increase tumor infiltrating lymphocytes infiltration into tumor spheroids without altering the expression of adhesion molecules.

Conclusions

Our results demonstrate that A2BAR is a promising target in immunotherapy, identifying ISAM-R56A as the most potent candidate for A2BAR blockade. Inhibition of A2BAR signaling restores T cell function and proliferation. Furthermore, A2BAR and dual A2AAR/A2BAR antagonists showed similar or better results than A2AAR antagonist AZD-4635 reinforcing the idea of dominant role of the A2BAR in the regulation of the immune system.
Functional tremor developing after successful MRI-guided focused ultrasound thalamotomy for essential tremor
Authors: Alshimemeri Sohaila , Vargas-Méndez Daniel , Chen Robert , Lipsman Nir , Schwartz M L , Lozano Andres M , Fasano Alfonso
Published: May 2022

Objective

To describe a case of functional tremor occurring after a successful MR-guided focused ultrasound thalamotomy (MRgFUS) for essential tremor.

Methods

A 71-year-old right-handed man with essential tremor was referred to us for consideration of deep brain stimulation surgery for worsening bilateral upper limb tremor after a successful left MRgFUS for essential tremor.

Results

On clinical exam, signs compatible with a functional tremor were noted, including entertainability and suppressibility. Electrophysiological studies were consistent with essential tremor and superimposed tremor fulfilling the laboratory-supported criteria for functional tremor.

Discussion

We describe the first reported case of a functional movement disorder occurring after successful MRgFUS procedure for essential tremor. Recognising this entity and its development after such therapeutic interventions is essential to avoid further unnecessary invasive therapies.
Cerebellar atrophy and its implications on gait in cerebral amyloid angiopathy
Authors: Horn Mitchell J , Gokcal Elif , Becker Alex J , Das Alvin S , Warren Andrew D ,   Alzheimer Disease Neuroimaging Initiative, Schwab Kristin , Goldstein Joshua. N , Biffi Alessandro , Rosand Jonathan , Polimeni Jonathan R , Viswanathan Anand , Greenberg Steven M , Gurol M Edip
Published: May 2022

Objective

Recent data suggest that cerebral amyloid angiopathy (CAA) causes haemorrhagic lesions in cerebellar cortex as well as subcortical cerebral atrophy. However, the potential effect of CAA on cerebellar tissue loss and its clinical implications have not been investigated.

Methods

Our study included 70 non-demented patients with probable CAA, 70 age-matched healthy controls (HCs) and 70 age-matched patients with Alzheimer’s disease (AD). The cerebellum was segmented into percent of cerebellar subcortical volume (pCbll-ScV) and percent of cerebellar cortical volume (pCbll-CV) represented as percent (p) of estimated total intracranial volume. We compared pCbll-ScV and pCbll-CV between patients with CAA, HCs and those with AD. Gait velocity (metres/second) was used to investigate gait function in patients with CAA.

Results

Patients with CAA had significantly lower pCbll-ScV compared with both HC (1.49±0.1 vs 1.73±0.2, p<0.001) and AD (1.49±0.1 vs 1.66 ± 0.24, p<0.001) and lower pCbll-CV compared with HCs (6.03±0.5 vs 6.23±0.6, p=0.028). Diagnosis of CAA was independently associated with lower pCbll-ScV compared with HCs (p<0.001) and patients with AD (p<0.001) in separate linear regression models adjusted for age, sex and presence of hypertension. Lower pCbll-ScV was independently associated with worse gait velocity (β=0.736, 95% CI 0.28 to 1.19, p=0.002) in a stepwise linear regression analysis including pCbll-CV along with other relevant variables.

Interpretation

Patients with CAA show more subcortical cerebellar atrophy than HC or patients with AD and more cortical cerebellar atrophy than HCs. Reduced pCbll-ScV correlated with lower gait velocity in regression models including other relevant variables. Overall, this study suggests that CAA causes cerebellar injury, which might contribute to gait disturbance.