bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term functioning status of COVID-19 survivors: a prospective observational evaluation of a cohort of patients surviving hospitalisation
Authors: Battistella Linamara Rizzo , Imamura Marta , De Pretto Lucas Ramos , Van Cauwenbergh Simon K H A A , Delgado Ramos Vinicius , Saemy Tome Uchiyama Sabrina , Matheus Denise , Kuhn Flavia , Amaral de Oliveira Ana Alice , Souza Naves Gabriella , Rossetti Mirisola Aline , de Quadros Ribeiro Fernando , Tadeu Sugawara Andre , Cantarino Mauricio , Andrade Santos Antunes Cavalca Rafael , Pagano Vanessa , Valentim Marques Melina , Mendes da Silva Elizabeth , Pereira Gomes Alessandra , Fregni Felipe
Published: July 2022

Objectives

The study investigated the long-term functional status of hospitalised COVID-19 survivors to explore and document their functional situation.

Design

This prospective observational study assessed 801 COVID-19 survivors at 3–11 months after hospital discharge. It analyses participants' sociodemographic background, COVID-19 clinical manifestations, and clinical and functional evaluations.

Setting

Tertiary-level university hospital in São Paulo, Brazil.

Participants

Study participants are COVID-19 survivors admitted to hospital care for at least 24 hours to treat acute SARS-CoV-2 infection.

Outcome measures

Epworth Sleepiness Scale, EuroQoL-5 Dimensions-5 Levels, Functional Assessment of Chronic Illness Therapy–Fatigue, Functional Independence Measure, Functional Oral Intake Scale, Handgrip Strength, Insomnia Severity Index, Medical Research Council (MRC) Dyspnea Scale, MRC sum score, Modified Borg Dyspnea Scale, pain Visual Analogue Scale, Post-COVID-19 Functional Status, Timed Up and Go, WHO Disability Assessment Schedule 2.0, 1-Minute Sit to Stand Test.

Results

Many participants required invasive mechanical ventilation (41.57%, 333 of 801). Mean age was 55.35±14.58 years. With a mean of 6.56 (SD: 1.58; 95% CI: 6.45 to 6.67) months after hospital discharge, 70.86% (567 of 800) reported limited daily activities, which were severe in 5.62% (45 of 800). They also reported pain and discomfort (64.50%, 516 of 800), breathlessness (64.66%, 514 of 795), and anxiety and depression (57.27%, 457 of 798). Daytime sleepiness and insomnia evaluations showed subthreshold results. Most (92.85%, 727 of 783) participants reported unrestricted oral intake. Data indicated no generalised fatigue (mean score: 39.18, SD: 9.77; 95% CI: 38.50 to 39.86). Assessments showed poor handgrip strength (52.20%, 379 of 726) and abnormal Timed Up and Go results (mean 13.07 s, SD: 6.49). The invasive mechanical ventilation group seemed to have a better handgrip strength however. We found no clear trends of change in their functional status during months passed since hospital discharge.

Conclusions

Muscle weakness, pain, anxiety, depression, breathlessness, reduced mobility, insomnia and daytime sleepiness were the most prevalent long-term conditions identified among previously hospitalised COVID-19 survivors.
Smart phone-based transcutaneous electrical acupoint stimulation as adjunctive therapy for hypertension (STAT-H trial): protocol for a cluster randomised controlled trial
Authors: Tu Jian-Feng , Kang Si-Bo , Wang Li-Qiong , Yan Shi-Yan , Yan Chao-Qun , Su Xin-Tong , Shi Guang-Xia , Mi Bao-Hong , Lin Ying , Wang Yu , Li He-Wen , Wang Xue-Zhou , Wang Xiao , Yang Jing-Wen , Liu Cun-Zhi
Published: July 2022

Introduction

Hypertension is a common risk factor for cardiovascular disease. Transcutaneous electrical acupoint stimulation (TEAS) may be effective for hypertension, but the evidence remains limited. The aim of this study is to evaluate the effectiveness and safety of the smart phone-based TEAS as adjunctive therapy for hypertension.

Methods and analysis

This study is a 52-week cluster randomised controlled trial with 1600 hypertension patients in 32 community health service centres. Patients who meet the inclusion criteria will be randomised into usual care group or TEAS group in a 1:1 ratio. All patients will be provided with usual care as recommended by the guidelines. In addition to this, patients in the TEAS group will receive non-invasive acupoint electrical stimulation for 30 min at home, 4 times weekly for 12 weeks. The primary outcome will be the mean difference in the changes in office systolic blood pressure from baseline to 12 weeks between TEAS and usual care groups. Secondary outcomes will include the change of mean diastolic blood pressure, proportion of patients with controlled blood pressure (blood pressure <140/90 mm Hg), proportion of patients taking antihypertensive drugs, change in number of antihypertensive drugs and changes in 12-item Short-Form. Tertiary outcomes will include change in body mass index, change in waist circumference, physical activity and medication adherence. Safety outcomes will be any serious adverse events and clinical events.

Ethics and dissemination

This study has been approved by ethics committee of Beijing University of Chinese Medicine (No. 2020BZHYLL0104). Written informed consent will be obtained from all patients before randomisation. Trial results will be disseminated in peer-reviewed publications.

Trial registration number

ChiCTR2000039400.
Estimation of tuberculosis incidence at subnational level using three methods to monitor progress towards ending TB in India, 2015–2020
Authors: Jeyashree Kathiresan , Thangaraj Jeromie , Rade Kiran , Modi Bhavesh , Selvaraju Sriram , Velusamy Saravanakumar , Akhil Sasidharan , Vijayageetha Mathavaswami , Sudha Rani Dhanapal , Sabarinathan Ramasamy , Manikandanesan Sakthivel , Elumalai Rajalakshmi , Natarajan Meenakumari , Joseph Bency , Mahapatra Amarendra , Shamim Almas , Shah Amar , Bhardwaj Ashok , Purty Anil , Vadera Bhavin , Sridhar Anand , Chowdhury Aniket , Shafie Asif , Choudhury Avijit , Dhrubjyoti Deka , Solanki Hardik , Sirmanwar Krushna , Khaparde Kshitij , Parmar Malik , Dahiya Nisha , Debdutta Parija , Ahmed Quazi , Ramachandran Ranjani , Prasad Ranjeet , Shinde Rohini , Baruah Rupali , Chauhan Sandeep , Bharaswadkar Sandip , Achanta Shanta , Sharath Burugina Nagaraja , Balakrishnan Shibu , Chandra Shivani , Khumukcham Sophia , Mandal Sudarsan , Chalil Sumitha , Shah Vaibhav , Roddawar Venkatesh , Rao Raghuram , Sachdeva Kuldeep , Murhekar Manoj
Published: July 2022

Objectives

We verified subnational (state/union territory (UT)/district) claims of achievements in reducing tuberculosis (TB) incidence in 2020 compared with 2015, in India.

Design

A community-based survey, analysis of programme data and anti-TB drug sales and utilisation data.

Setting

National TB Elimination Program and private TB treatment settings in 73 districts that had filed a claim to the Central TB Division of India for progress towards TB-free status.

Participants

Each district was divided into survey units (SU) and one village/ward was randomly selected from each SU. All household members in the selected village were interviewed. Sputum from participants with a history of anti-TB therapy (ATT), those currently experiencing chest symptoms or on ATT were tested using Xpert/Rif/TrueNat. The survey continued until 30 Mycobacterium tuberculosis cases were identified in a district.

Outcome measures

We calculated a direct estimate of TB incidence based on incident cases identified in the survey. We calculated an under-reporting factor by matching these cases within the TB notification system. The TB notification adjusted for this factor was the estimate by the indirect method. We also calculated TB incidence from drug sale data in the private sector and drug utilisation data in the public sector. We compared the three estimates of TB incidence in 2020 with TB incidence in 2015.

Results

The estimated direct incidence ranged from 19 (Purba Medinipur, West Bengal) to 1457 (Jaintia Hills, Meghalaya) per 100 000 population. Indirect estimates of incidence ranged between 19 (Diu, Dadra and Nagar Haveli) and 788 (Dumka, Jharkhand) per 100 000 population. The incidence using drug sale data ranged from 19 per 100 000 population in Diu, Dadra and Nagar Haveli to 651 per 100 000 population in Centenary, Maharashtra.

Conclusion

TB incidence in 1 state, 2 UTs and 35 districts had declined by at least 20% since 2015. Two districts in India were declared TB free in 2020.
Gendered impact of COVID-19 containment measures on unpaid care work and mental health in Europe: a scoping review protocol
Authors: Gencer Hande , Brunnett Regina , Marchwacka Maria A , Rattay Petra , Staiger Tobias , Tezcan-Güntekin Hürrem , Pöge Kathleen
Published: July 2022

Introduction

Women are more likely than men to provide unpaid care work. Previous research has shown that lack of support for various forms of unpaid care work and work-family conflicts have negative impacts on caregivers’ mental health, especially among female caregivers. COVID-19 containment measures may exacerbate existing gender inequalities both in terms of unpaid care work and adverse mental health outcomes. This scoping review protocol describes the systematic approach to review published literature from March 2020 onwards to identify empirical studies and grey literature on the mental health impact of COVID-19 containment measures on subgroups of unpaid caregivers at the intersection of gender and other categories of social difference (eg, ethnicity, age, class) in Europe.

Methods and analysis

This scoping review is informed and guided by Arksey and O’Malley’s methodological framework. We will search the databases Medline, PsycINFO, Scopus, CINAHL, Social Sciences Abstracts, Sociological Abstracts as well as Applied Social Sciences Index & Abstracts (ASSIA) and hand-search reference lists of selected articles to identify relevant peer-reviewed studies. We will conduct a grey literature search using Google Scholar and targeted hand-search on known international and European websites and include reports, working papers, policy briefs and book chapters that meet the inclusion criteria. Studies that report gender-segregated findings for mental health outcomes associated with unpaid care work in the context of COVID-19 containment measures in Europe will be included. Two reviewers will independently screen all abstracts and full texts for inclusion, and extract general information, study characteristics and relevant findings. Results will be synthesized narratively.

Ethics and dissemination

This study is a review of published literature; ethics approval is not warranted. The findings of this study will inform public health research and policy. The results will be disseminated through a peer-reviewed publication and conference presentations.
The International Vitreoretinal B-Cell Lymphoma Registry: a protocol paper
Authors: Smith Justine R , Farrall Alexandra L , Davis Janet L , de Boer Joke H , Hall Anthony J , Mochizuki Manabu , Sen H Nida , Takase Hiroshi , ten Dam-van Loon Ninette H , Touitou Valérie , Vasconcelos-Santos Daniel V , Wilson David J , Yeh Steven , Radford Mark H B
Published: July 2022

Introduction

Vitreoretinal lymphoma is a rare ocular cancer with high morbidity and mortality despite treatment. Diagnosis by cytopathology is often delayed, and various molecular and image-based investigations have been developed. Diverse treatments are used, but there is a limited medical evidence to differentiate their effectiveness. We designed an international registry that would collect diagnostic, treatment and outcomes data, to establish new evidence for the management of this cancer.

Methods and analysis

The International Vitreoretinal B-Cell Lymphoma Registry will accrue data retrospectively for individuals aged 18 years or older, diagnosed with new or recurrent vitreoretinal B-cell lymphoma on or after 1 January 2020. A steering committee of subspecialised ophthalmologists identified 20 key clinical data items that describe patient demographics, tissue involvements, diagnostic testing, ocular and systemic treatments and treatment complications, and visual acuity and survival outcomes. Customised software was designed to permit collection of these data across a single baseline and multiple follow-up forms. The platform collects data without identifiers and at 3 month reporting intervals. Outcomes of the project will include: (1) descriptions of clinical presentations, and diagnostic and therapeutic preferences; (2) associations between clinical presentations, and diagnostics and treatments, and between diagnostics and treatments (assessed by ORs with 95% CIs); and (3) estimations of rates of vision loss, and progression-free and overall survival (assessed by Kaplan-Meier estimates).

Ethics and dissemination

The registry has received Australia-wide approval by a national human research ethics committee. Sites located outside Australia are required to seek local human research ethics review. Results generated through the registry will be disseminated primarily by peer-reviewed publications that are expected to inform clinical practice, as well as educational materials.
COVID-19 morbidity in Afghanistan: a nationwide, population-based seroepidemiological study
Authors: Saeedzai Sayed Ataullah , Sahak Mohammad Nadir , Arifi Fatima , Abdelkreem Aly Eman , Gurp Margo van , White Lisa J , Chen Siyu , Barakat Amal , Azim Giti , Rasoly Bahara , Safi Soraya , Flegg Jennifer A , Ahmed Nasar , Ahadi Mohmmad Jamaluddin , Achakzai Niaz M , AbouZeid Alaa
Published: July 2022

Objective

The primary objectives were to determine the magnitude of COVID-19 infections in the general population and age-specific cumulative incidence, as determined by seropositivity and clinical symptoms of COVID-19, and to determine the magnitude of asymptomatic or subclinical infections.

Design, setting and participants

We describe a population-based, cross-sectional, age-stratified seroepidemiological study conducted throughout Afghanistan during June/July 2020. Participants were interviewed to complete a questionnaire, and rapid diagnostic tests were used to test for SARS-CoV-2 antibodies. This national study was conducted in eight regions of Afghanistan plus Kabul province, considered a separate region. The total sample size was 9514, and the number of participants required in each region was estimated proportionally to the population size of each region. For each region, 31–44 enumeration areas (EAs) were randomly selected, and a total of 360 clusters and 16 households per EA were selected using random sampling. To adjust the seroprevalence for test sensitivity and specificity, and seroreversion, Bernoulli’s model methodology was used to infer the population exposure in Afghanistan.

Outcome measures

The main outcome was to determine the prevalence of current or past COVID-19 infection.

Results

The survey revealed that, to July 2020, around 10 million people in Afghanistan (31.5% of the population) had either current or previous COVID-19 infection. By age group, COVID-19 seroprevalence was reported to be 35.1% and 25.3% among participants aged ≥18 and 5–17 years, respectively. This implies that most of the population remained at risk of infection. However, a large proportion of the population had been infected in some localities, for example, Kabul province, where more than half of the population had been infected with COVID-19.

Conclusion

As most of the population remained at risk of infection at the time of the study, any lifting of public health and social measures needed to be considered gradually.
How can competencies in minor surgery in general practice be increased? Assessing the effect of a compact intervention in postgraduate training: a mixed-methodsstudy
Authors: Schwill Simon , Krug Katja , Poppleton Aaron , Reith Dorothee , Senft Jonas D , Szecsenyi Joachim , Stengel Sandra
Published: July 2022

Objectives

We aimed to assess general practice (GP) trainees’ self-perception of surgical competencies and to explore longitudinal effects of a compact intervention.

Design

We performed a mixed-methods study including a before and after comparison in the intervention group (IG), a comparison of attendees and non-attendees (control group (CG)) and a qualitative evaluation of the intervention. Competencies were self-assessed through surveys. Semi-structured interviews were performed after 9 months.

Setting

In 2019, a 2-day voluntary seminar focussing on minor surgery/injuries was offered on 13 occasions by educators from KWBW Verbundweiterbildungplus (Competence Centre for Postgraduate Medical Education Baden-Württemberg).

Participants

All enrolled GP trainees were offered participation. GP trainees who did not attend a seminar (non-attendees) were recruited for CG after the 13th intervention.

Intervention

Attendees took part in an interactive, GP-oriented short course incorporating 270 min of focused minor surgery/injuries training (compact intervention) on the second day of the 2-day seminar.

Results

326 GP trainees (IG: n=257; CG: n=69) participated in the study. 17 attendees were interviewed. CG had more often experienced a surgical rotation (p=0.03) and reported higher interest in performing minor surgery in future practice (p=0.03). GP trainees self-rated their all-round competency in minor surgery as average (IG: 3.0±1.0, CG: 3.2±0.9, IG:CG p=0.06). After the intervention, attendees felt that surgical skills should be a core component of GP vocational training (p=0.05). After 9 months, attendees remembered a variety of content and valued the interactive, case-oriented, peer-to-peer approach in a mixed learning group. Some attendees reported they had started to overcome competency gaps in minor surgery.

Conclusions

A compact intervention in minor surgery provides an ‘intense’ stimulus which could foster positive attitudes towards minor surgery and promote longitudinal personal development of related competencies in GP trainees, including those with little interest in surgery. Such measures appear crucial to support individual progress of GP trainees to provide comprehensive primary care.
Interaction effect between overweight/obesity and alcohol consumption on hypertension risk in China: a longitudinal study
Authors: Sun Jiaru , Wang Xiaoqin , Terry Paul D , Ren Xiaohan , Hui Zhaozhao , Lei Shuangyan , Wang Caihua , Wang Mingxu
Published: July 2022

Objective

To explore the interaction effect between overweight/obesity and alcohol consumption on hypertension risk.

Design

A longitudinal study of the independent and combined effects of hypertension risk factors.

Setting

Twelve provinces in China, including Beijing Liaoning, Heilongjiang, Shanghai, Jiangsu, Shandong, Henan, Hubei, Hunan, Guangxi, Guizhou and Chongqing.

Participants

Longitudinal data of China Health and Nutrition Survey, collected between 2011 and 2015, were used in this study. A total of 13 121 residents from 12 provinces were included and completed physical examinations and questionnaires at baseline.

Outcome

First incidence of hypertension.

Results

Over a mean follow-up of 4 years, 690 incident hypertension cases were reported. After adjusting for age, gender, education level, marital status, physical activity, diabetes and smoking, high body mass index (BMI) and light drinking (OR=5.07, 95% CI 3.06 to 8.41), high waist circumference (WC) and light drinking (OR=4.81, 95% CI 2.92 to 7.91), high waist hip ratio and light drinking (OR=2.85, 95% CI 1.84 to 4.42) were the highest risk of all participants in the three combinations. Multiplicative interaction measures were statistically significant in overweight/obesity and drinking/light drinking/heavy drinking categories in men (p<0.05). Additive interactions were observed between high BMI and drinking in men (relative excess risk due to interaction=1.75, 95% CI 0.85 to 2.65, attributable proportion due to interaction=0.56, 95% CI 0.36 to 0.76, synergy index=6.43, 95% CI 1.02 to 28.84).

Conclusions

Measures of body weight and size, particularly BMI and WC, appear to interact synergistically with alcohol consumption to increase the risk of hypertension in the Chinese population. Given that approximately 245 million people in China have hypertension, and that hypertension is a major cause of cardiovascular disease worldwide, our results may have implications for chronic disease prevention.
Frailty assessment tools for use by surgeons when evaluating older adults prior to surgery: a scoping review protocol
Authors: Chesney Tyler R , Wong Camilla , Tricco Andrea C , Wijeysundera Duminda N , Ladha Karim Shiraz , Kishibe Teruko , Dubé Samuel , Puts Martine T E , Alibhai Shabbir M H , Daza Julian F
Published: July 2022

Introduction

Despite growing evidence, uncertainty persists about which frailty assessment tools are best suited for routine perioperative care. We aim to understand which frailty assessment tools perform well and are feasible to implement.

Methods and analysis

Using a registered protocol following Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA), we will conduct a scoping review informed by the Joanna Briggs Institute Guide for Scoping Reviews and reported using PRISMA extension for Scoping Reviews recommendations. We will develop a comprehensive search strategy with information specialists using the Peer Review of Electronic Search Strategies checklist, and implement this across relevant databases from 2005 to 13 October 2021 and updated prior to final review publication. We will include all studies evaluating a frailty assessment tool preoperatively in patients 65 years or older undergoing intracavitary, non-cardiac surgery. We will exclude tools not assessed in clinical practice, or using laboratory or radiologic values alone. After pilot testing, two reviewers will independently assess information sources for eligibility first by titles and abstracts, then by full-text review. Two reviewers will independently chart data from included full texts using a piloted standardised electronic data charting. In this scoping review process, we will (1) index frailty assessment tools evaluated in the preoperative clinical setting; (2) describe the level of investigation supporting each tool; (3) describe useability of each tool and (4) describe direct comparisons between tools. The results will inform ready application of frailty assessment tools in routine clinical practice by surgeons and other perioperative clinicians.

Ethics and dissemination

Ethic approval is not required for this secondary data analysis. This scoping review will be published in a peer-review journal. Results will be used to inform an ongoing implementation study focused on geriatric surgery to overcome the current lack of uptake of older adult-oriented care recommendations and ensure broad impact of research findings.
Australian children’s foot, ankle and leg problems in primary care: a secondary analysis of the Bettering the Evaluation and Care of Health (BEACH) data
Authors: Williams Cylie M , Menz Hylton B , Lazzarini Peter A , Gordon Julie , Harrison Christopher
Published: July 2022

Objectives

To explore children’s foot, ankle and leg consultation patterns and management practices in Australian primary care.

Design

Cross-sectional, retrospective study.

Setting

Australia Bettering the Evaluation and Care of Health program dataset.

Participants

Data were extracted for general practitioners (GPs) and patients<18 years from April 2000 to March 2016 inclusive.

Main outcome measures

Demographic characteristics: sex, GP age groups (ie, <45, 45–54, 55+ years), GP country of training, patient age grouping (0–4, 5–9, 10–14, 15–18 years), postcode, concession card status, indigenous status, up to three patient encounter reasons, up to four encounter problems/diagnoses and the clinical management actioned by the GP.

Results

Children’s foot, ankle or leg problems were managed at a rate of 2.05 (95% CI 1.99 to 2.11) per 100 encounters during 229 137 GP encounters with children. There was a significant increase in the rate of foot, ankle and leg problems managed per 100 children in the population, from 6.1 (95% CI 5.3 to 6.8) in 2005–2006 to 9.0 (95% CI 7.9 to 10.1) in 2015–2016. Management of children’s foot, ankle and leg problems were independently associated with male patients (30% more than female), older children (15–18 years were 7.1 times more than <1 years), male GPs (13% more) and younger GPs (<45 years of age 13% more than 55+). The top four most frequently managed problems were injuries (755.9 per 100 000 encounters), infections (458.2), dermatological conditions (299.4) and unspecified pain (176.3). The most frequently managed problems differed according to age grouping.

Conclusions

Children commonly present to GPs for foot, ankle and leg problems. Presentation frequencies varied according to age. Unexpectedly, conditions presenting commonly in adults, but rarely in children, were also frequently recorded. This data highlights the importance of initiatives supporting contemporary primary care knowledge of diagnoses and management of paediatric lower limb problems to minimise childhood burden of disease.
Vitrectomy combined with lens capsule flap transplantation in the treatment of high myopia macular hole retinal detachment: study protocol for a prospective randomised controlled trial
Authors: Gong Qiaoyun , Ye Luyao , Wu Xia , Xue Lin , Zhou Hao , Fan Ying , Xu Xun , Wang Weijun , Qian Tianwei
Published: July 2022

Introduction

Vitrectomy combined with internal limiting membrane (ILM) peeling, flap or tamponade is widely used in the treatment of macular diseases, such as macular hole (MH) and high myopia macular hole retinal detachment (HMMHRD). However, movement of the ILM to a suitable position to prevent displacement is a difficult operation. Improving visual function after surgery remains controversial. Compared with ILM, the thicker and more flexible lens capsule is easy to obtain and operate. Previous studies have confirmed the effectiveness of lens capsule flap in the treatment of MH. This study aims to evaluate the efficacy and safety of vitrectomy combined with lens capsule flap transplantation in the treatment of HMMHRD.

Methods and analysis

This single-centre, single-blind, prospective, randomised clinical trial will include 54 patients with HMMHRD who will first undergo phacoemulsification and intraocular lens implantation and then vitrectomy combined with lens capsule flap transplantation (experimental group) or ILM tamponade (control group). Study participants will be randomly allocated in a 1:1 ratio to experimental and control groups. Follow-up will be conducted 1, 3 and 7 days and 1, 3 and 6 months after surgery in both groups. Necessary examinations will be performed at each follow-up visit. Measurement outcomes include postoperative situation of macular hole closure, best-corrected visual acuity, macular retinal function and macular retinal sensitivity. The primary outcome is type I closure rate of MH 6 months after operation. Intergroup comparisons of the proportions of patients with type I closure of MH will be performed with Fisher’s exact test.

Ethics and dissemination

Full ethics approval for this study was obtained from the Ethics Committee of Shanghai General Hospital, Shanghai Jiaotong University, Shanghai, China. The outcomes of the trial will be disseminated through peer-reviewed journals and at scientific conferences.

Trial registration number

ChiCTR2200057836.
Helping healthcare teams to debrief effectively: associations of debriefers’ actions and participants’ reflections during team debriefings
Authors: Kolbe Michaela , Grande Bastian , Lehmann-Willenbrock Nale , Seelandt Julia Carolin
Published: July 2022

Background

Debriefings help teams learn quickly and treat patients safely. However, many clinicians and educators report to struggle with leading debriefings. Little empirical knowledge on optimal debriefing processes is available. The aim of the study was to evaluate the potential of specific types of debriefer communication to trigger participants’ reflection in debriefings.

Methods

In this prospective observational, microanalytic interaction analysis study, we observed clinicians while they participated in healthcare team debriefings following three high-risk anaesthetic scenarios during simulation-based team training. Using the video-recorded debriefings and INTERACT coding software, we applied timed, event-based coding with DE-CODE, a coding scheme for assessing debriefing interactions. We used lag sequential analysis to explore the relationship between what debriefers and participants said. We hypothesised that combining advocacy (ie, stating an observation followed by an opinion) with an open-ended question would be associated with participants’ verbalisation of a mental model as a particular form of reflection.

Results

The 50 debriefings with overall 114 participants had a mean duration of 49.35 min (SD=8.89 min) and included 18 486 behavioural transitions. We detected significant behavioural linkages from debriefers’ observation to debriefers’ opinion (z=9.85, p<0.001), from opinion to debriefers’ open-ended question (z=9.52, p<0.001) and from open-ended question to participants’ mental model (z=7.41, p<0.001), supporting our hypothesis. Furthermore, participants shared mental models after debriefers paraphrased their statements and asked specific questions but not after debriefers appreciated their actions without asking any follow-up questions. Participants also triggered reflection among themselves, particularly by sharing personal anecdotes.

Conclusion

When debriefers pair their observations and opinions with open-ended questions, paraphrase participants’ statements and ask specific questions, they help participants reflect during debriefings.
Predictors of longer-term depression trajectories during the COVID-19 pandemic: a longitudinal study in four UK cohorts
Authors: Rosa Lara , Godwin Hayward J , Cortese Samuele , Brandt Valerie
Published: July 2022

Background

The COVID-19 pandemic has caused an increase in mental ill health compared with prepandemic levels. Longer-term trajectories of depression in adults during the pandemic remain unclear.

Objective

We used latent growth curve modelling to examine individual trajectories of depression symptoms, and their predictors, beyond the early stage of the pandemic.

Methods

Data were collected in three waves in May 2020, September/October 2020 and February/March 2021 in four UK cohorts (Millennium Cohort Study, Next Steps cohort, British Cohort and National Child Development Study). We included n=16 978 participants (mean age at baseline: 20, 30, 50 and 62, respectively). Self-reported depressive symptoms were the study outcome.

Findings

Symptoms of depression were higher in younger compared with older age groups (d=0.7) across all waves. While depressive symptoms remained stable from May 2020 to Autumn 2020 overall (standardized mean difference (SMD)=0.03, 95% CI 0.02 to 0.04), they increased in all age groups from May 2020 to Spring 2021 (SMD=0.12, 95% CI 0.11 to 0.13). Feelings of loneliness were the strongest predictor and concurrent correlate of increasing depressive symptoms across all cohorts, prepandemic mental health problems and having a long-term illness were also significantly associated with an increase in depression symptoms across all ages. By contrast, compliance with social distancing measures did not predict an increase in depression symptoms.

Conclusions

Feeling lonely and isolated had a large effect on depression trajectories across all generations, while social distancing measures did not.

Clinical implications

These findings highlight the importance of fostering the feeling of connectedness during COVID-19-related distancing measures.
Chimeric antigen receptor T cells engineered to recognize the P329G-mutated Fc part of effector-silenced tumor antigen-targeting human IgG1 antibodies enable modular targeting of solid tumors
Authors: Stock Sophia , Benmebarek Mohamed-Reda , Kluever Anna-Kristina , Darowski Diana , Jost Christian , Stubenrauch Kay-Gunnar , Benz Joerg , Freimoser-Grundschober Anne , Moessner Ekkehard , Umana Pablo , Subklewe Marion , Endres Stefan , Klein Christian , Kobold Sebastian
Published: July 2022

Background

Chimeric antigen receptor (CAR) T cell therapy has proven its clinical utility in hematological malignancies. Optimization is still required for its application in solid tumors. Here, the lack of cancer-specific structures along with tumor heterogeneity represent a critical barrier to safety and efficacy. Modular CAR T cells indirectly binding the tumor antigen through CAR-adaptor molecules have the potential to reduce adverse events and to overcome antigen heterogeneity. We hypothesized that a platform utilizing unique traits of clinical grade antibodies for selective CAR targeting would come with significant advantages. Thus, we developed a P329G-directed CAR targeting the P329G mutation in the Fc part of tumor-targeting human antibodies containing P329G L234A/L235A (LALA) mutations for Fc silencing.

Methods

A single chain variable fragment-based second generation P329G-targeting CAR was retrovirally transduced into primary human T cells. These CAR T cells were combined with IgG1 antibodies carrying P329G LALA mutations in their Fc part targeting epidermal growth factor receptor (EGFR), mesothelin (MSLN) or HER2/neu. Mesothelioma, pancreatic and breast cancer cell lines expressing the respective antigens were used as target cell lines. Efficacy was evaluated in vitro and in vivo in xenograft mouse models.

Results

Unlike CD16-CAR T cells, which bind human IgG in a non-selective manner, P329G-targeting CAR T cells revealed specific effector functions only when combined with antibodies carrying P329G LALA mutations in their Fc part. P329G-targeting CAR T cells cannot be activated by an excess of human IgG. P329G-directed CAR T cells combined with a MSLN-targeting P329G-mutated antibody mediated pronounced in vitro and in vivo antitumor efficacy in mesothelioma and pancreatic cancer models. Combined with a HER2-targeting antibody, P329G-targeting CAR T cells showed substantial in vitro activation, proliferation, cytokine production and cytotoxicity against HER2-expressing breast cancer cell lines and induced complete tumor eradication in a breast cancer xenograft mouse model. The ability of the platform to target multiple antigens sequentially was shown in vitro and in vivo.

Conclusions

P329G-targeting CAR T cells combined with antigen-binding human IgG1 antibodies containing the P329G Fc mutation mediate pronounced in vitro and in vivo effector functions in different solid tumor models, warranting further clinical translation of this concept.
Axenfeld-Rieger syndrome: more than meets the eye
Authors: Reis Linda M. , Maheshwari Mohit , Capasso Jenina , Atilla Huban , Dudakova Lubica , Thompson Samuel , Zitano Lia , Lay-Son Guillermo , Lowry R. Brian , Black Jennifer , Lee Joseph , Shue Ann , Kremlikova Pourova Radka , Vaneckova Manuela , Skalicka Pavlina , Jedlickova Jana , Trkova Marie , Williams Bradley , Richard Gabriele , Bachman Kristine , Seeley Andrea H. , Costakos Deborah , Glaser Thomas M , Levin Alex V. , Liskova Petra , Murray Jeffrey C. , Semina Elena V.
Published: July 2022

Background

Axenfeld-Rieger syndrome (ARS) is characterised by typical anterior segment anomalies, with or without systemic features. The discovery of causative genes identified ARS subtypes with distinct phenotypes, but our understanding is incomplete, complicated by the rarity of the condition.

Methods

Genetic and phenotypic characterisation of the largest reported ARS cohort through comprehensive genetic and clinical data analyses.

Results

128 individuals with causative variants inPITX2orFOXC1, including 81 new cases, were investigated. Ocular anomalies showed significant overlap but with broader variability and earlier onset of glaucoma forFOXC1-related ARS. Systemic anomalies were seen in all individuals withPITX2-related ARS and the majority of those withFOXC1-related ARS.PITX2-related ARS demonstrated typical umbilical anomalies and dental microdontia/hypodontia/oligodontia, along with a novel high rate of Meckel diverticulum.FOXC1-related ARS exhibited characteristic hearing loss and congenital heart defects as well as previously unrecognised phenotypes of dental enamel hypoplasia and/or crowding, a range of skeletal and joint anomalies, hypotonia/early delay and feeding disorders with structural oesophageal anomalies in some. Brain imaging revealed highly penetrant white matter hyperintensities, colpocephaly/ventriculomegaly and frequent arachnoid cysts. The expanded phenotype ofFOXC1-related ARS identified here was found to fully overlap features of De Hauwere syndrome. The results were used to generate gene-specific management plans for the two types of ARS.

Conclusion

Since clinical features of ARS vary significantly based on the affected gene, it is critical that families are provided with a gene-specific diagnosis,PITX2-related ARS orFOXC1-related ARS. De Hauwere syndrome is proposed to be a FOXC1opathy.
Thrombus radiomics in patients with anterior circulation acute ischemic stroke undergoing endovascular treatment
Authors: van Voorst Henk , Bruggeman Agnetha A E , Yang Wenjin , Andriessen Jurr , Welberg Elise , Dutra Bruna G , Konduri Praneeta R , Arrarte Terreros Nerea , Hoving Jan W , Tolhuisen Manon L , Kappelhof Manon , Brouwer Josje , Boodt Nikki , van Kranendonk Katinka R , Koopman Miou S , Hund Hajo M , Krietemeijer Menno , van Zwam Wim H , van Beusekom Heleen M M , van der Lugt Aad , Emmer Bart J , Marquering Henk A , Roos Yvo B W E M , Caan Matthan W A , Majoie Charles B L M
Published: July 2022

Background

Thrombus radiomics (TR) describe complex shape and textural thrombus imaging features. We aimed to study the relationship of TR extracted from non-contrast CT with procedural and functional outcome in endovascular-treated patients with acute ischemic stroke.

Methods

Thrombi were segmented on thin-slice non-contrast CT (≤1 mm) from 699 patients included in the MR CLEAN Registry. In a pilot study, we selected 51 TR with consistent values across two raters’ segmentations (ICC >0.75). Random forest models using TR in addition or as a substitute to baseline clinical variables (CV) and manual thrombus measurements (MTM) were trained with 499 patients and evaluated on 200 patients for predicting successful reperfusion (extended Thrombolysis in Cerebral Ischemia (eTICI) ≥2B), first attempt reperfusion, reperfusion within three attempts, and functional independence (modified Rankin Scale (mRS) ≤2). Three texture and shape features were selected based on feature importance and related to eTICI ≥2B, number of attempts to eTICI ≥2B, and 90-day mRS with ordinal logistic regression.

Results

Random forest models using TR, CV or MTM had comparable predictive performance. Thrombus texture (inverse difference moment normalized) was independently associated with reperfusion (adjusted common OR (acOR) 0.85, 95% CI 0.72 to 0.99). Thrombus volume and texture were also independently associated with the number of attempts to successful reperfusion (acOR 1.36, 95% CI 1.03 to 1.88 and acOR 1.24, 95% CI 1.04 to 1.49).

Conclusions

TR describing thrombus volume and texture were associated with more attempts to successful reperfusion. Compared with models using CV and MTM, TR had no added value for predicting procedural and functional outcome.
National reduction in cerebral arteriovenous malformation treatment correlated with increased rupture incidence
Authors: Luther Evan , McCarthy David J , Burks Joshua , Govindarajan Vaidya , Lu Victor M , Silva Michael , Lang Michael , Gross Bradley A , Starke Robert M
Published: July 2022

Background

Recently, there has been a shift in management of unruptured cerebral arteriovenous malformations (AVMs) following studies suggesting that medical management alone was superior to interventional therapy.

Objective

To evaluate the influence of contemporary AVM management on AVM rupture patterns in the United States.

Methods

154 297 AVM admissions were identified between 2003 and 2017 in the National Inpatient Sample. Annual AVM intervention and rupture rates were computed and multivariable logistic regression assessed the likelihood of AVM intervention pre- and post-2014. Segmented regression identified significant change points and fitted segmented linear models for annual intervention and rupture rates. Correlation coefficients assessed the relationship between annual AVM intervention and rupture rates.

Results

For unruptured AVMs, intervention likelihood and proportion decreased after 2014 (28.1% to 22.3%, p<0.0001; adjusted OR=0.857, 95% CI 0.751 to 0.977, p=0.02). Ruptured AVM admissions increased from 14.7% to 18.6% after 2014 (p<0.0001). Between 2003 and 2017, segmented linear regression identified one significant change point in intervention rate between 2014 and 2015. Average annual percent change for rupture incidence and intervention rate increased by 0.49% (p=0.0001) and decreased by 1.17% (p=0.0001), respectively. Annual AVM intervention rates were inversely correlated with annual AVM rupture incidence (Pearson coefficient=−0.82, p=0.0002). In 2017, the annual AVM rupture rate (20.6%) surpassed the annual AVM intervention rate (19.7%).

Conclusions

After 2014, the likelihood of intervention for unruptured AVMs decreased while the incidence of ruptured AVMs increased. These findings suggest that fewer unruptured AVM treatments may lead to increases in AVM rupture incidence.
Long-term effect of field triage on times to endovascular treatment for emergent large vessel occlusion
Authors: Jayaraman Mahesh V , Baird Grayson , Oueidat Karim , Paolucci Gino , Haas Richard A , Torabi Radmehr , Moldovan Krisztina , Rhodes Jason , Potvin John , Alexander-Scott Nicole , Yaghi Shadi , Madsen Tracy , Furie Karen , McTaggart Ryan A
Published: July 2022

Background

Delays to endovascular therapy (EVT) for stroke may be mitigated with direct field triage to EVT centers. We sought to compare times to treatment over a 5.5 year span between two adjacent states, one with field triage and one without, served by a single comprehensive stroke center (CSC).

Methods

During the study period, one of the two states implemented severity-based triage for suspected emergent large vessel occlusion, while in the other state, patients were transported to the closest hospital regardless of severity. We compared times to treatment and clinical outcomes between these two states. We also performed a matched pairs analysis, matching on date treated and distance from field to CSC.

Results

639 patients met the inclusion criteria, 407 in State 1 (with field triage) and 232 in State 2 (without field triage). In State 1, scene to EVT decreased 6% (or 8.13 min, p=0.0004) every year but no decrease was observed for State 2 (<1%, p=0.94). Cumulatively over 5.5 years, there was a reduction of 43 min in time to EVT in State 1, but no change in State 2. Lower rates of disability were seen in State 1, both for the entire cohort (all OR 1.22, 95% CI 1.07 to 1.40, p=0.0032) and for those independent at baseline (1.36, 95% CI 1.15 to 1.59, p=0.0003).

Conclusions

Comparing adjacent states over time, the implementation of severity-based field triage significantly reduced time to EVT.
Global impact of the COVID-19 pandemic on subarachnoid haemorrhage hospitalisations, aneurysm treatment and in-hospital mortality: 1-year follow-up
Authors:   SVIN COVID-19 Global SAH Registry
Published: July 2022

Background

Prior studies indicated a decrease in the incidences of aneurysmal subarachnoid haemorrhage (aSAH) during the early stages of the COVID-19 pandemic. We evaluated differences in the incidence, severity of aSAH presentation, and ruptured aneurysm treatment modality during the first year of the COVID-19 pandemic compared with the preceding year.

Methods

We conducted a cross-sectional study including 49 countries and 187 centres. We recorded volumes for COVID-19 hospitalisations, aSAH hospitalisations, Hunt-Hess grade, coiling, clipping and aSAH in-hospital mortality. Diagnoses were identified by International Classification of Diseases, 10th Revision, codes or stroke databases from January 2019 to May 2021.

Results

Over the study period, there were 16 247 aSAH admissions, 344 491 COVID-19 admissions, 8300 ruptured aneurysm coiling and 4240 ruptured aneurysm clipping procedures. Declines were observed in aSAH admissions (−6.4% (95% CI −7.0% to −5.8%), p=0.0001) during the first year of the pandemic compared with the prior year, most pronounced in high-volume SAH and high-volume COVID-19 hospitals. There was a trend towards a decline in mild and moderate presentations of subarachnoid haemorrhage (SAH) (mild: −5% (95% CI −5.9% to –4.3%), p=0.06; moderate: −8.3% (95% CI −10.2% to –6.7%), p=0.06) but no difference in higher SAH severity. The ruptured aneurysm clipping rate remained unchanged (30.7% vs 31.2%, p=0.58), whereas ruptured aneurysm coiling increased (53.97% vs 56.5%, p=0.009). There was no difference in aSAH in-hospital mortality rate (19.1% vs 20.1%, p=0.12).

Conclusion

During the first year of the pandemic, there was a decrease in aSAH admissions volume, driven by a decrease in mild to moderate presentation of aSAH. There was an increase in the ruptured aneurysm coiling rate but neither change in the ruptured aneurysm clipping rate nor change in aSAH in-hospital mortality.

Trial registration number

NCT04934020.
Superior effects of natalizumab versus other DMTs on patient-reported outcomes in people with multiple sclerosis
Authors: Chen Jing , Diouf Ibrahima , Taylor Bruce V , Kalincik Tomas , van der Mei Ingrid
Published: July 2022

Background

Little is known about the comparative effectiveness of multiple sclerosis (MS) disease-modifying therapies (DMTs) on patient-reported outcomes in MS. We compared the effects of natalizumab to other DMTs in relation to MS symptom severity, quality of life, disability, disease progression and employment outcomes using real-world data.

Methods

We included 2817 observations in 2015, 2016 and 2017 from 1382 participants in the Australian MS Longitudinal Study. Information on treatment, health and employment outcomes was prospectively collected by questionnaires. Marginal structural models with interaction terms for DMT×time were used to compare natalizumab and other comparator treatment groups.

Results

Natalizumab was associated with improvements over time, or general trends of improvement, in the severity of many symptoms and work productivity loss. Compared with any other DMTs, natalizumab was associated with superior effects over time for 8 of 23 patient-reported outcomes, with similar directions of effect observed for another 6, demonstrating consistency. There were no differences in effect for spasticity, fatigue, pain, feelings of depression, disability, European quality of life five dimension index, presenteeism and work status. Natalizumab did not perform significantly worse over time compared with any other DMTs for any of the outcomes.

Conclusions

Natalizumab was associated with superior outcomes over time for many patient-reported health and employment outcomes when compared with other DMTs in this large prospective cohort study. These findings may influence treatment selection in clinical practice and future treatment cost-effectiveness analyses.