bluuebunny/crossref_metadata_2025 huggingface dataset:
Residual and local influence analyses for unit gamma regressions
Authors: S. Rocha Suelena , L. Espinheira Patrícia , Cribari‐Neto Francisco
Published: November 2020

We obtain local influence measures and residuals for the unit gamma regression model. In particular, we introduce four residuals that are based on Fisher's iterative scoring parameter estimation algorithm and develop local influence analysis based on several different perturbation schemes: cases weighting, response additive perturbation, and covariate(s) additive perturbation. An empirical application in which variables related to education and investment in research and development are used to explain the proportion of nonpoor people in a set of countries is presented and discussed. Residual and local influence analyses show that the unit gamma regression model yields a good fit to the data, even outperforming the beta regression model. The diagnostic analysis singles out countries whose data are worthy of further investigation. Our results reveal that lower poverty levels are associated with higher shares of investment in high technology. The statistical significance of such a relationship is not sensitive to atypical data points.
Training for health ministry: Design and implementation of library resources to incorporate health education and promotion into theological education
Authors: Fuller Tyler J. , Bogue Sarah
Published: November 2020

This case study leverages existing library assets and curated educational resources for students, pastors, and health ministers by seeking to increase their understandings of how religion intersects with, and informs, health education and promotion, and public health more broadly, while equipping them with tools to engage in important conversations about health ministry. This article describes and evaluates a library‐based research guide that is a replicable model for collaborative ministerial training about engaging, evaluating, and participating in health education and promotion, which is a vital component of theological education. Much of the pedagogical conversation around religion and health within theological and religious studies has focused on the ways that religion assists in the socio‐cultural construction of health and healing. This case study expands on this conversation by detailing how seminary students, pastors, and health ministers can also use public health knowledge to better provide services to their congregations and communities. This model provides long‐term, publicly‐available, asynchronous access to these materials, making it a valuable resource for theology schools.
Witnessing ice habitat collapse in the Arctic
Authors: Vincent Warwick F. , Mueller Derek
Published: November 2020

Abrupt ice loss signals major changes ahead in a north polar conservation zone
Purse strings, patients, and personal glory
The Mutant Project
Eben Kirksey
St. Martin's Press, 2020. 304 pp.
Authors: Güttinger Stephan
Published: November 2020

An anthropologist investigates the factors shaping modern genetic medicine
Learning to think long-term
Deep Time Reckoning: How Future Thinking Can Help Earth Now
Vincent Ialenti
MIT Press, 2020. 208 pp.
Authors: Hamblin Jacob Darwin
Published: November 2020

Lessons from nuclear waste management could help us move beyond shortsighted climate thinking
Modeling, post COVID-19
Authors: Press William H. , Levin Richard C.
Published: November 2020

Much of the public first learned about epidemiological modeling during the early months of the coronavirus disease 2019 (COVID-19) pandemic. The first models resulted in more confusion than clarity. Even though coronavirus cases were rising exponentially in the United States and Europe, some models predicted a rapid peak followed by a rapid decline, whereas other models predicted cycles of infection continuing over several years. Much has been learned since those early months. In retrospect, it is clear that modeling requires both reliable data and an accurate understanding of how disease spreads, and that the field of epidemiological modeling requires a diversity of approaches. Support for this field must increase and be coordinated, with a designation of responsibilities among funding agencies.
Mobile robotic platforms for the acoustic tracking of deep-sea demersal fishery resources
Authors: Masmitja I. , Navarro J. , Gomariz S. , Aguzzi J. , Kieft B. , O’Reilly T. , Katija K. , Bouvet P. J. , Fannjiang C. , Vigo M. , Puig P. , Alcocer A. , Vallicrosa G. , Palomeras N. , Carreras M. , del Rio J. , Company J. B.
Published: November 2020

Mobile robots enhance traditional acoustic tracking methods to study the spatiotemporal behavior of deep-sea fishery resources.
Antitumor activity without on-target off-tumor toxicity of GD2–chimeric antigen receptor T cells in patients with neuroblastoma
Authors: Straathof Karin , Flutter Barry , Wallace Rebecca , Jain Neha , Loka Thalia , Depani Sarita , Wright Gary , Thomas Simon , Cheung Gordon Weng-Kit , Gileadi Talia , Stafford Sian , Kokalaki Evangelia , Barton Jack , Marriott Clare , Rampling Dyanne , Ogunbiyi Olumide , Akarca Ayse U. , Marafioti Teresa , Inglott Sarah , Gilmour Kimberly , Al-Hajj Muhammad , Day William , McHugh Kieran , Biassoni Lorenzo , Sizer Natalie , Barton Claire , Edwards David , Dragoni Ilaria , Silvester Julie , Dyer Karen , Traub Stephanie , Elson Lily , Brook Sue , Westwood Nigel , Robson Lesley , Bedi Ami , Howe Karen , Barry Ailish , Duncan Catriona , Barone Giuseppe , Pule Martin , Anderson John
Published: November 2020

Patients with neuroblastoma infused with GD2-directed CAR-T cells experienced immune activation and transient tumor regressions without neurotoxicity.
A Bioinformatic Pipeline for Improved Genome Analysis and Clustering of Isolates during Outbreaks of Legionnaires' Disease
Authors: Haas Wolfgang , Lapierre Pascal , Musser Kimberlee A.
Published: November 2020

Legionnaires’ disease, a severe lung infection caused by the bacterium
Legionella pneumophila
, occurs as single cases or in outbreaks that are actively tracked by public health departments. To determine the point source of an outbreak, clinical isolates need to be compared to environmental samples to find matching isolates.
Pregnancy cohorts and biobanking in sub-Saharan Africa: a systematic review
Authors: Bone Jeffrey N , Pickerill Kelly , Woo Kinshella Mai-Lei , Vidler Marianne , Craik Rachel , Poston Lucilla , Stones William , Sevene Esperanca , Temmerman Marleen , Koech Etyang Angela , Roca Anna , Russell Donna , Tribe Rachel M , von Dadelszen Peter , Magee Laura A
Published: November 2020

Background

Technological advances and high throughput biological assays can facilitate discovery science in biobanks from population cohorts, including pregnant women. Biological pathways associated with health outcomes differ depending on geography, and high-income country data may not generalise to low-resource settings. We conducted a systematic review to identify prospective pregnancy cohorts in sub-Saharan Africa (SSA) that include biobanked samples with potential to enhance discovery science opportunity.

Methods

Inclusion criteria were prospective data collection during pregnancy, with associated biobanking in SSA. Data sources included: scientific databases (with comprehensive search terms), grey literature, hand searching applicable reference lists and expert input. Results were screened in a three-stage process based on title, abstract and full text by two independent reviewers. The review is registered on PROSPERO (CRD42019147483).

Results

Fourteen SSA studies met the inclusion criteria from database searches (n=8), reference list searches (n=2) and expert input (n=4). Three studies have ongoing data collection. The most represented countries were South Africa and Mozambique (Southern Africa) (n=3), Benin (Western Africa) (n=4) and Tanzania (Eastern Africa) (n=4); including an estimated 31 763 women. Samples commonly collected were blood, cord blood and placenta. Seven studies collected neonatal samples. Common clinical outcomes included maternal and perinatal mortality, malaria and preterm birth.

Conclusions

Increasingly numerous pregnancy cohorts in SSA that include biobanking are generating a uniquely valuable resource for collaborative discovery science, and improved understanding of the high regional risks of maternal, fetal and neonatal morbidity and mortality. Future studies should align protocols and consider their added value and distinct contributions.
Allocation of funding into blast injury-related research and blast traumatic brain injury between 2000 and 2019: analysis of global investments from public and philanthropic funders
Authors: Denny J W , Brown R J , Head M G , Batchelor J , Dickinson A S
Published: November 2020

Introduction

There is little systematic tracking or detailed analysis of investments in research and development for blast injury to support decision-making around research future funding.

Methods

This study examined global investments into blast injury-related research from public and philanthropic funders across 2000–2019. Research databases were searched using keywords, and open data were extracted from funder websites. Data collected included study title, abstract, award amount, funder and year. Individual awards were categorised to compare amounts invested into different blast injuries, the scientific approaches taken and analysis of research investment into blast traumatic brain injury (TBI).

Results

A total of 806 awards were identified into blast injury-related research globally, equating to US$902.1 million (m, £565.9m GBP). There was a general increase in year-on-year investment between 2003 and 2009 followed by a consistent decline in annual funding since 2010. Pre-clinical research received $671.3 m (74.4%) of investment. Brain-related injury research received $427.7 m (47.4%), orthopaedic injury $138.6 m (15.4%), eye injury $63.7 m (7.0%) and ear injury $60.5m (6.7%). Blast TBI research received a total investment of $384.3 m, representing 42.6% of all blast injury-related research. The U.S. Department of Defense funded $719.3 m (80%).

Conclusions

Investment data suggest that blast TBI research has received greater funding than other blast injury health areas. The funding pattern observed can be seen as reactive, driven by the response to the War on Terror, the rising profile of blast TBI and congressionally mandated research.
Is the perceived impact of disciplinary procedures on medical doctors’ professional practice associated with working in an open culture and feeling supported? A questionnaire among medical doctors in the Netherlands who have been disciplined
Authors: Laarman Berber S , Bouwman Renée J R , de Veer Anke J E , Friele Roland D
Published: November 2020

Introduction

Disciplinary procedures can have a negative impact on the professional functioning of medical doctors. In this questionnaire study, doctors’ experience with open culture and support during a disciplinary procedure is studied to determine whether open culture and support are associated with perceived changes in the professional practice of doctors.

Methods

All doctors who received a warning or a reprimand from the Dutch Medical Disciplinary Board between July 2012 and August 2016 were invited to fill in a 60-item questionnaire concerning open culture, perceived support during the disciplinary procedure and the impact of the procedure on professional functioning as reported by doctors themselves. The response rate was 43% (n=294).

Results

A majority of doctors perceive their work environment as a safe environment in which to talk about and report incidents (71.2% agreed). Respondents felt supported by a lawyer or legal representative and colleagues (92.8% and 89.2%, respectively). The disciplinary procedure had effects on professional practice. Legal support and support from a professional confidant and a professional association were associated with fewer perceived changes to professional practice.

Conclusion

Our study shows that doctors who had been disciplined perceive their working environment as open. Doctors felt supported by lawyers and/or legal representatives and colleagues. Legal support was associated with less of a perceived impact on doctors’ professional practice.
Nurse-led, screening-triggered, early specialised palliative care intervention programme for patients with advanced lung cancer: study protocol for a multicentre randomised controlled trial
Authors: Fujisawa Daisuke , Umemura Shigeki , Okizaki Ayumi , Satomi Eriko , Yamaguchi Takuhiro , Miyaji Tempei , Mashiko Tomoe , Kobayashi Naoko , Kinoshita Hiroya , Mori Masanori , Morita Tatsuya , Uchitomi Yosuke , Goto Koichi , Ohe Yuichiro , Matsumoto Yoshihisa
Published: November 2020

Introduction

It has been suggested that palliative care integrated into standard cancer treatment from the early phase of the disease can improve the quality of life of patients with cancer. In this paper, we present the protocol for a multicentre randomised controlled trial to examine the effectiveness of a nurse-led, screening-triggered, early specialised palliative care intervention programme for patients with advanced lung cancer.

Methods and analysis

A total of 206 patients will be randomised (1:1) to the intervention group or the control group (usual care). The intervention, triggered with a brief self-administered screening tool, comprises comprehensive need assessments, counselling and service coordination by advanced-level nurses. The primary outcome is the Trial Outcome Index of the Functional Assessment of Cancer Therapy (FACT) at 12 weeks. The secondary outcomes include participants’ quality of life (FACT-Lung), depression (Patient Health Questionnaire-9), anxiety (Generalized Anxiety Disorder-7), illness perception (Prognosis and Treatment Perceptions Questionnaire), medical service use and survival. A mixed-method approach is expected to provide an insight about how this intervention works.

Ethics and dissemination

This study has been approved by the Institutional Review Board of the National Cancer Center Japan (approval number: 2016-235). The findings will be disseminated through peer-reviewed publications and conference presentations and will be reflected on to the national healthcare policy.

Trial registration number

UMIN000025491.
Estimation of minimally important difference of the EQ-5D-5L utility scores among patients with either hypertension or diabetes or both: a cross-sectional study in Hong Kong
Authors: XU Richard Huan , WONG Eliza Lai-yi , CHEUNG Annie Wai-ling
Published: November 2020

Objective

To estimate and report the minimally important difference (MID) of the EuroQol five-dimensional five-level questionnaire (EQ-5D-5L) using the Hong Kong (HK) utility score among patients with either hypertension or diabetes or both.

Design

Data were analysed using secondary data analysis based on a cross-sectional study assessing patients’ experiences in HK.

Setting

A representative sample was recruited from 26 specialist outpatient clinics in HK.

Participants

We analysed data from 2231 and 662 patients who reported having hypertension or diabetes alone, respectively, and 874 patients had these two diseases.

Intervention

An instrument-defined approach was applied to estimate MID stratified according to sex and age for the three subpopulations.

Results

The overall MID (oMID) estimates were 0.089, 0.086 and 0.089 for patients with hypertension or diabetes alone and with these two diseases, respectively. The adjusted MID (aMID) estimate was smaller than the oMID, and the improved MID was larger than the deteriorated MID. Women had larger oMID but smaller aMID than men. Younger respondents had larger aMID than older respondents. Effect sizes ranged from 0.30 to 0.503, which fit our preset criteria.

Conclusion

Four types of MID of the EQ-5D utility score for patients with hypertension or diabetes alone and with these two diseases were reported. Variations in the MID estimates should be further explored in other populations or using different statistical methods.
Delayed healthcare seeking and prolonged illness in healthcare workers during the COVID-19 pandemic: a single-centre observational study
Authors: de Wilton Angus , Kilich Eliz , Chaudhry Zain , Bell Lucy CK , Gahir Joshua , Cadman Jane , Lever Robert A , Logan Sarah A
Published: November 2020

Objectives

To describe a cohort of self-isolating healthcare workers (HCWs) with presumed COVID-19.

Design

A cross-sectional, single-centre study.

Setting

A large, teaching hospital based in Central London with tertiary infection services.

Participants

236 HCWs completed a survey distributed by internal staff email bulletin. 167 were women and 65 men.

Measures

Information on symptomatology, exposures and health-seeking behaviour were collected from participants by self-report.

Results

The 236 respondents reported illness compatible with COVID-19 and there was an increase in illness reporting during March 2020 Diagnostic swabs were not routinely performed. Cough (n=179, 75.8%), fever (n=138, 58.5%), breathlessness (n=84, 35.6%) were reported. Anosmia was reported in 42.2%. Fever generally settled within 1 week (n=110/138, 88%). Several respondents remained at home and did not seek formal medical attention despite reporting severe breathlessness and measuring hypoxia (n=5/9, 55.6%). 2 patients required hospital admission but recovered following oxygen therapy. 84 respondents (41.2%) required greater than the obligated 7 days off work and 9 required greater than 3 weeks off.

Conclusion

There was a significant increase in staff reporting illness compatible with possible COVID-19 during March 2020. Subsequent serology studies at the same hospital study site have confirmed sero-positivity for COVID-19 up to 45% by the end of April 2020 in frontline HCWs. The study revealed a concerning lack of healthcare seeking in respondents with significant red flag symptoms (severe breathlessness, hypoxia). This study also highlighted anosmia as a key symptom of COVID-19 early in the pandemic, prior to this symptom being more widely recognised as a feature of COVID-19.
Proton pump inhibitor utilisation and potentially inappropriate prescribing analysis: insights from a single-centred retrospective study
Authors: Liu Yujuan , Zhu Xian , Li Rongxin , Zhang Jun , Zhang Feng
Published: November 2020

Objectives

This study aimed to characterise the prescribing patterns and evaluate the appropriateness of the prescribed proton pump inhibitors (PPIs) in adult patients via a review of electronic medical records in a single-centred hospital.

Design

All patients admitted to the outpatient department of Jinshan Hospital, Fudan University, Shanghai, between 1 January 2018 and 31 December 2018 were evaluated. Individuals aged 18 years or above and with at least one dispensing for PPIs were identified as PPI users. New PPI users were defined as a subject who did not receive any dispensing for PPIs in the year prior to the index date. Baseline characteristics of PPI users and their therapies were described by treatment indication, economic indicators and co-prescription, overall and separately.

Setting

The prescription database was retrieved from the hospital information system of Jinshan Hospital, Fudan University.

Results

Among 18 435 identified PPI users in 2018, 14 219 patients (aged 18 years or above) who had at least one dispensing PPIs were new users (77%), and among them, men accounted for 47%. The mean treatment duration was 23 days. Omeprazole was the most commonly prescribed drug. PPIs are inappropriately prescribed in 50% (13 589/25 850) of prescriptions. Prescription appropriateness analysis indicated that the unapproved indications for PPI new users accounted for 47%; among them, the proportion of gastritis diagnosis was 34%. The proportion of PPI new users with co-prescription of glucocorticosteroids (GCs) who have risk factors accounted for 24% and lower than other co-prescription. A majority of PPI users (73%) reported high-dose PPI prescription. The defined daily dose of oral pantoprazole was the highest, and injectable omeprazole had the highest defined daily cost. In contrast, only the drug utilisation index value of oral esomeprazole was less than 1.0.

Conclusion

The results indicate the challenge of PPI use was accompanied by unapproved indications, frequent inappropriate co-prescription with GCs and excessive dosages. Efforts should be paid to promote rational use and ensure the choice of suitable PPI therapy in the future.
The Schulthess local Shoulder Arthroplasty Registry (SAR): cohort profile
Authors: Marzel Alex , Schwyzer Hans-Kaspar , Kolling Christoph , Moro Fabrizio , Flury Matthias , Glanzmann Michael C , Jung Christian , Wirth Barbara , Weber Beatrice , Simmen Beat , Scheibel Markus , Audigé Laurent
Published: November 2020

Purpose

Clinical registries are essential for evaluation of surgical outcomes. The Schulthess Shoulder Arthroplasty Registry (SAR) was established in 2006 to evaluate safety, function, quality-of-life and patient satisfaction in patients undergoing shoulder arthroplasty.

Participants

Adult patients undergoing anatomic or reverse shoulder joint replacement at the Schulthess Klinik, a high-volume, leading orthopaedic surgery centre in Zürich, Switzerland.

Findings to date

Between March 2006 and December 2019, the registry covered 98% of eligible operations. Overall, 2332 patients were enrolled with a total of 2796 operations and 11 147 person-years of follow-up. Mean age at baseline was 71 (range: 20–95), 65% were women. Most common indication was rotator cuff tears with osteoarthritis (42%) and the mean preoperative Constant Score was 31 (±15). The most frequent arthroplasty type was reverse, increasing from 61% in 2006–2010 to 86% in 2015–2019. Functional recovery peaked at 12-month postoperatively and did not show a clinically relevant deterioration during the first ten follow-up years. Since its establishment, the registry was used to address multiple pertinent clinical and methodological questions. Primary focus was on comparing different implant configurations (eg, glenosphere diameter) and surgical techniques (eg, latissimus dorsi transfer) to maximise functional recovery. Additionally, the cohort contributed to the determination of the clinical relevance and validity of radiological monitoring of cortical bone resorption and scapular notching. Finally, SAR data helped to demonstrate that returning to sports was among key patient expectations after reverse shoulder arthroplasty.

Future plans

As first patients are approaching the 15 years follow-up landmark, the registry will continue providing essential data on long-term functional outcomes, implant stability, revision rates and aetiologies as well as patient satisfaction and quality-of-life. In addition to research and quality-control, the cohort data will be brought back to the patients by bolstering real-time clinical decision support.
Cost-effectiveness analysis of adding ramucirumab to the first-line erlotinib treatment for untreated EGFR-mutated metastatic non-small cell lung cancer in China
Authors: Liu Qiao , Luo Xia , Peng Liubao , Yi Lidan , Wan Xiaomin , Zeng Xiaohui , Tan Chongqing
Published: November 2020

Objective

To investigate the cost-effectiveness of ramucirumab plus erlotinib compared with placebo plus erlotinib in the first-line setting for patients with EGFR-mutated metastatic non-small cell lung cancer (mNSCLC) from the Chinese healthcare system perspective.

Design

A Markov model consisting of three health states using clinical survival data from the RELAY phase III randomised clinical trial, a lifetime horizon for costs and quality-adjusted life-years (QALYs) was constructed to analyse the cost-effectiveness of ramucirumab plus erlotinib. One-way and probabilistic sensitivity analyses were performed to evaluate the robustness of the model. Additional price reduction scenario analyses were performed.

Setting

The Chinese healthcare system perspective.

Participants

A hypothetical Chinese cohort of patients with confirmed previously documented ex19del or Leu858Arg mutation stage IV NSCLC, and without known epidermal growth factor receptor (EGFR) Thr790Met mutation and central nervous system metastases.

Interventions

Ramucirumab plus erlotinib versus placebo plus erlotinib.

Primary outcome measure

Costs, QALYs, incremental cost-effectiveness ratio (ICER).

Results

In base-case analysis, ramucirumab plus erlotinib yield an additional 4.21 QALYs at a cost of $540 590, resulting in an ICER of $128 302/QALY. In price reduction scenario analysis, the ICER ($65 227/QALY) was decreased significantly when the National Reimbursement Drug List (NRDL) negotiation was available for ramucirumab, and the ICER ($131 554/QALY) was increased slightly when the NRDL negotiation was unavailable for erlotinib. Sensitivity analyses demonstrated our results to be most sensitive to the unit cost of ramucirumab (10 mg/kg), and more than 52.1% reduction in the price of ramucirumab resulted in the ICER under the willingness-to-pay threshold set for affluent regions ($70 353/QALY).

Conclusions

Ramucirumab plus erlotinib is unlikely to be cost-effective for patients with untreated EGFR-mutated mNSCLC in China. Reducing the price of ramucirumab through the National Healthcare Security Administration negotiation was found to be the most realistic action to improve cost-effectiveness.
Utilisation of diagnostics in India: a rapid ethnographic study exploring context and behaviour
Authors: Holloway Bronwen , Mathur Aditya , Pathak Ashish , Bergström Anna
Published: November 2020

Objectives

To explore factors that influence behaviour in the utilisation of diagnostics by caregivers of sick children. Utilisation is defined as a caregiver assisting a child to get diagnostic tests done and return for follow-up of results. Understanding these experiences may help inform the development of interventions and implementation strategies to improve the use of diagnostics, thereby target treatment and optimise antibiotic use.

Design

A rapid ethnographic qualitative study using 3 months of unstructured observations, 1 month of structured observations of diagnostic utilisation and 43 semi-structured interviews. Transcripts were coded and analysed using inductive thematic analysis. Findings were explored from a behavioural perspective through the lens of the ‘Capability, Opportunity, Motivation and Behaviour’ (COM-B) model for understanding behaviour. The multiple methods of investigation applied allowed for triangulation and cross-validation of the findings.

Setting

The paediatric outpatient department of a teaching hospital in rural, central India.

Participants

Caregivers of sick children attending the paediatric outpatient department who were sent for one or more diagnostic test.

Results

Three key themes were identified that influenced caregivers’ behaviour. Caregivers trusted and understood the importance of diagnostics but their acceptance wavered depending on the severity of illness and preference to treat their child directly with medicines. Caregivers struggled to access diagnostics, describing delays in testing, receiving results and follow-up, further complicated by travel time, distance and competing priorities such as work. Diagnostics were relatively cheap compared with other healthcare facilities however, the cost of the test, travel expenses and wages lost for missing work, were barriers to getting the tests done and returning for follow-up.

Conclusions

Diagnostics are generally accepted and their purpose understood, however, the organisation of diagnostic services, direct and indirect costs hinder caregivers from using diagnostics. Improvements in accessibility and affordability may increase caregiver motivation to use diagnostics and return for follow-up.
Prevalence, care-seeking practices and impact of self-reported vision impairment in Southwest Cameroon: a community-based study
Authors: Mbeboh Susan N , Christie Sabrinah Ariane , Carvalho Melissa , Dickson Drusia , Nana Theophile , Embolo Frida , Dicker Rochelle , Juillard Catherine , Chichom Mefire Alain
Published: November 2020

Objectives

To establish the prevalence of self-reported vision impairment (VI) in Southwest Cameroon and describe associated care-seeking practices, functional limitations and economic hardships.

Design

A three-stage clustered sampling household community-based survey.

Setting

The Southwest region of Cameroon.

Participants

8046 individuals of all ages residing in the Southwest region of Cameroon.

Primary and secondary outcome measures

Prevalence of self-reported VI, onset of vision loss, care-seeking practices, diagnosis and treatment, functional limitations, economic hardships on household, beliefs about surgical treatability of blindness and barriers to surgical care.

Results

The estimated prevalence of self-reported VI in Southwest Cameroon was 0.87% (95% CI 0.62 to 1.21). Among participants aged ≥40 years, the prevalence increased to 2.61% (95% CI 1.74 to 3.90). Less than a quarter of affected participants reported difficulty working (20.5%) or trouble going to school (12.0%) as a result of their VI. Yet, over half (52%, n=43) of affected households experienced significant economic hardships due to the VI. Residing in an urban setting (aOR 1.16, 95% CI 1.04 to 1.30) and belonging to a higher socioeconomic status (aOR 1.13, 95% CI 1.02 to 1.26) were factors associated with the belief that certain types of blindness were surgically reversible. Formal care was not sought by 16.3% (n=8) of affected participants. Cataracts was the leading diagnosis among participants who did seek formal care (43.2%, n=16), although 93.8% of these cases were not surgically treated, primarily due to a lack of perceived need.

Conclusion

The prevalence of individuals who report vision impairment in Southwest Cameroon is considerably lower than prior published estimates based on visual physical examinations. Routine community-level screening and cost financing schemes could improve detection of pre-clinical eye disease and the utilisation of surgical care. It could also pre-empt disability and economic hardships associated with advanced VI in the region.
Assessment of the concordance between individual-level and area-level measures of socio-economic deprivation in a cancer patient cohort in England and Wales
Authors: Ingleby Fiona C , Belot Aurélien , Atherton Iain , Baker Matthew , Elliss-Brookes Lucy , Woods Laura M
Published: November 2020

Objectives

Most research on health inequalities uses aggregated deprivation scores assigned to the small area where the patient lives; however, the concordance between aggregate area-level deprivation measures and personal deprivation experienced by individuals living in the area is poorly understood. Our objective was to examine the agreement between individual and ecological deprivation. We tested the concordance between metrics of income, occupation and education at individual and area levels, and assessed the reliability of area-based deprivation measures to predict individual deprivation circumstances.

Setting

England and Wales.

Participants

A cancer patient cohort of 9547 individuals extracted from the Office
for National Statistics Longitudinal Study.

Outcomes

We quantified the concordance between measures of income, occupation and education at individual and area level. In addition, we used ROC (receiver
operating characteristic) curves and the area under the curve (AUC) to assess the reliability of area-based deprivation measures to predict individual deprivation circumstances.

Results

We found low concordance between individual-level and area-level indicators of deprivation (Cramer’s V statistics range between 0.07 and 0.20). The most commonly used indicator in health inequalities research, area-based income deprivation, was a poor predictor of individual income status (AUC between 0.56 and 0.59), whereas education and occupation were slightly better predictors (AUC between 0.62 and 0.65). The results were consistent across sexes and across six major cancer types.

Conclusions

Our results indicate that ecological deprivation measures capture only part of the relationship between deprivation and health outcomes, especially with respect to income measurement. This has important implications for our understanding of the relationship between deprivation and health, and, as a consequence, healthcare policy. The results have a wide-reaching impact for the way in which we measure and monitor inequalities, and in turn, fund and organise current UK healthcare policy aimed at reducing them.
Experiences of Venous Leg Ulcer persons following an individualised nurse-led education: protocol for a qualitative study using a constructivist grounded theory approach
Authors: Bobbink Paul , Larkin Philip J , Probst Sebastian
Published: November 2020

Introduction

Venous leg ulcers are slow-healing wounds with a high risk of recurrences. To prevent recurrences and promote healing, different nurse-led educational interventions have been developed. The impact of these interventions on self-management is ambiguous. Also, how persons with a venous leg ulcer experiences these educational sessions are poorly described.

Aim

This study protocol presents the methodology to provide a comprehensive explanation of participants’ journeys—of how they experience their individualised education sessions concerning self-management.

Methods and analysis

A constructivist grounded theory approach according to Charmaz involving 30 participants will be used. Data will be collected through semistructured face-to-face interviews. Interviews will be transcribed verbatim and analysed with initial and focus coding using MAXQDA. Data collection and data analysis will occur iteratively, focusing on constant comparison to obtain well-developed categories. Categories will be reinforced using existent literature.

Ethics and dissemination

This pre-results study is embedded in a clinical trial (NCT04019340) and approved by ethical committee of the canton of Geneva (CCER: 2019-01964). A theory will emerge from participants’ journeys informing future education sessions for patients with venous leg ulcers. The findings will be disseminated through peer-reviewed publications and communications.
COVID-19 in Pregnancy in Scotland (COPS): protocol for an observational study using linked Scottish national data
Authors: Stock Sarah Jane , McAllister David , Vasileiou Eleftheria , Simpson Colin R , Stagg Helen R , Agrawal Utkarsh , McCowan Colin , Hopkins Leanne , Donaghy Jack , Ritchie Lewis , Robertson Chris , Sheikh Aziz , Wood Rachael
Published: November 2020

Introduction

The effects of SARS-CoV-2 in pregnancy are not fully delineated. We will describe the incidence of COVID-19 in pregnancy at population level in Scotland, in a prospective cohort study using linked data. We will determine associations between COVID-19 and adverse pregnancy, neonatal and maternal outcomes and the proportion of confirmed cases of SARS-CoV-2 infection in neonates associated with maternal COVID-19.

Methods and analysis

Prospective cohort study using national linked data sets. We will include all women in Scotland, UK, who were pregnant on or became pregnant after, 1 March 2020 (the date of the first confirmed case of SARS-CoV-2 infection in Scotland) and all births in Scotland from 1 March 2020 onwards. Individual-level data will be extracted from data sets containing details of all livebirths, stillbirth, terminations of pregnancy and miscarriages and ectopic pregnancies treated in hospital or attending general practice. Records will be linked within the Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) platform, which includes primary care records, virology and serology results and details of COVID-19 Community Hubs and Assessment Centre contacts and deaths. We will perform analyses using definitions for confirmed, probable and possible COVID-19 and report serology results (where available). Outcomes will include congenital anomaly, miscarriage, stillbirth, termination of pregnancy, preterm birth, neonatal infection, severe maternal disease and maternal deaths. We will perform descriptive analyses and appropriate modelling, adjusting for demographic and pregnancy characteristics and the presence of comorbidities. The cohort will provide a platform for future studies of the effectiveness and safety of therapeutic interventions and immunisations for COVID-19 and their effects on childhood and developmental outcomes.

Ethics and dissemination

COVID-19 in Pregnancy in Scotland is a substudy of EAVE II(, which has approval from the National Research Ethics Service Committee. Findings will be reported to Scottish Government, Public Health Scotland and published in peer-reviewed journals.
National administrative record linkage between specialist community drug and alcohol treatment data (the National Drug Treatment Monitoring System (NDTMS)) and inpatient hospitalisation data (Hospital Episode Statistics (HES)) in England: design, method and evaluation
Authors: Roberts Emmert , Doidge James C , Harron Katie L , Hotopf Matthew , Knight Jonathan , White Martin , Eastwood Brian , Drummond Colin
Published: November 2020

Objectives

The creation and evaluation of a national record linkage between substance misuse treatment, and inpatient hospitalisation data in England.

Design

A deterministic record linkage using personal identifiers to link the National Drug Treatment Monitoring System (NDTMS) curated by Public Health England (PHE), and Hospital Episode Statistics (HES) Admitted Patient Care curated by National Health Service (NHS) Digital.

Setting and participants

Adults accessing substance misuse treatment in England between 1 April 2018 and 31 March 2019 (n=268 251) were linked to inpatient hospitalisation records available since 1 April 1997.

Outcome measures

Using a gold-standard subset, linked using NHS number, we report the overall linkage sensitivity and precision. Predictors for linkage error were identified, and inverse probability weighting was used to interrogate any potential impact on the analysis of length of hospital stay.

Results

79.7% (n=213 814) people were linked to at least one HES record, with an estimated overall sensitivity of between 82.5% and 83.3%, and a precision of between 90.3% and 96.4%. Individuals were more likely to link if they were women, white and aged between 46 and 60. Linked individuals were more likely to have an average length of hospital stay ≥5 days if they were men, older, had no fixed residential address or had problematic opioid use. These associations did not change substantially after probability weighting, suggesting they were not affected by bias from linkage error.

Conclusions

Linkage between substance misuse treatment and hospitalisation records offers a powerful new tool to evaluate the impact of treatment on substance related harm in England. While linkage error can produce misleading results, linkage bias appears to have little effect on the association between substance misuse treatment and length of hospital admission. As subsequent analyses are conducted, potential biases associated with the linkage process should be considered in the interpretation of any findings.
Tumors establish resistance to immunotherapy by regulating Tregrecruitment via CCR4
Authors: Marshall Lisa A , Marubayashi Sachie , Jorapur Aparna , Jacobson Scott , Zibinsky Mikhail , Robles Omar , Hu Dennis Xiaozhou , Jackson Jeffrey J , Pookot Deepa , Sanchez Jerick , Brovarney Martin , Wadsworth Angela , Chian David , Wustrow David , Kassner Paul D , Cutler Gene , Wong Brian , Brockstedt Dirk G , Talay Oezcan
Published: November 2020

Background

Checkpoint inhibitors (CPIs) such as anti-PD(L)-1 and anti-CTLA-4 antibodies have resulted in unprecedented rates of antitumor responses and extension of survival of patients with a variety of cancers. But some patients fail to respond or initially respond but later relapse as they develop resistance to immune therapy. One of the tumor-extrinsic mechanisms for resistance to immune therapy is the accumulation of regulatory T cells (Treg) in tumors. In preclinical and clinical studies, it has been suggested that tumor trafficking of Tregis mediated by CC chemokine receptor 4 (CCR4). Over 90% of human Tregexpress CCR4 and migrate toward CCL17 and CCL22, two major CCR4 ligands that are either high at baseline or upregulated in tumors on CPI treatment. Hence, CCR4 antagonism has the potential to be an effective antitumor treatment by reducing the accumulation of Treginto the tumor microenvironment (TME).

Methods

We developed in vitro and in vivo models to assess Tregmigration and antitumor efficacy using a potent and selective CCR4 antagonist, CCR4-351. We used two separate tumor models, Pan02 and CT26 mouse tumors, that have high and low CCR4 ligand expression, respectively. Tumor growth inhibition as well as the frequency of tumor-infiltrating Tregand effector T cells was assessed following the treatment with CCR4 antagonist alone or in combination with CPI.

Results

Using a selective and highly potent, novel small molecule inhibitor of CCR4, we demonstrate that migration of CCR4+Treginto the tumor drives tumor progression and resistance to CPI treatment. In tumor models with high baseline levels of CCR4 ligands, blockade of CCR4 reduced the number of Tregand enhanced antitumor immune activity. Notably, in tumor models with low baseline level of CCR4 ligands, treatment with immune CPIs resulted in significant increases of CCR4 ligands and Tregnumbers. Inhibition of CCR4 reduced Tregfrequency and potentiated the antitumor effects of CPIs.

Conclusion

Taken together, we demonstrate that CCR4-dependent Tregrecruitment into the tumor is an important tumor-extrinsic mechanism for immune resistance. Blockade of CCR4 led to reduced frequency of Tregand resulted in increased antitumor activity, supporting the clinical development of CCR4 inhibitors in combination with CPI for the treatment of cancer.

Statement of significance

CPI upregulates CCL17 and CCL22 expression in tumors and increases Tregmigration into the TME. Pharmacological antagonism of the CCR4 receptor effectively inhibits Tregrecruitment and results in enhanced antitumor efficacy either as single agent in CCR4 ligandhightumors or in combination with CPIs in CCR4 ligandlowtumors.
PODO447: a novel antibody to a tumor-restricted epitope on the cancer antigen podocalyxin
Authors: Canals Hernaez Diana , Hughes Michael R , Dean Pamela , Bergqvist Peter , Samudio Ismael , Blixt Ola , Wiedemeyer Katharina , Li Yicong , Bond Chris , Cruz Eric , Köbel Martin , Gilks Blake , Roskelley Calvin D , McNagny Kelly M
Published: November 2020

Background

The success of new targeted cancer therapies has been dependent on the identification of tumor-specific antigens. Podocalyxin (Podxl) is upregulated on tumors with high metastatic index and its presence is associated with poor outcome, thus emerging as an important prognostic and theragnostic marker in several human cancers. Moreover, in human tumor xenograft models, Podxl expression promotes tumor growth and metastasis. Although a promising target for immunotherapy, the expression of Podxl on normal vascular endothelia and kidney podocytes could hamper efforts to therapeutically target this molecule. Since pathways regulating post-translational modifications are frequently perturbed in cancer cells, we sought to produce novel anti-Podxl antibodies (Abs) that selectively recognize tumor-restricted glycoepitopes on the extracellular mucin domain of Podxl.

Methods

Splenic B cells were isolated from rabbits immunized with a Podxl-expressing human tumor cell line. Abs from these B cells were screened for potent reactivity to Podxl+neoplastic cell lines but not Podxl+primary endothelial cells. Transcripts encoding heavy and light chain variable regions from promising B cells were cloned and expressed as recombinant proteins. Tumor specificity was assessed using primary normal tissue and an ovarian cancer tissue microarray (TMA). Mapping of the tumor-restricted epitope was performed using enzyme-treated human tumor cell lines and a glycan array.

Results

One mAb (PODO447) showed strong reactivity with a variety of Podxl+ tumor cell lines but not with normal primary human tissue including Podxl+ kidney podocytes and most vascular endothelia. Screening of an ovarian carcinoma TMA (219 cases) revealed PODO447 reactivity with the majority of tumors, including 65% of the high-grade serous histotype. Subsequent biochemical analyses determined that PODO447 reacts with a highly unusual terminal N-acetylgalactosamine beta-1 (GalNAcβ1) motif predominantly found on the Podxl protein core. Finally, Ab–drug conjugates showed specific efficacy in killing tumor cellsin vitro.

Conclusions

We have generated a novel and exquisitely tumor-restricted mAb, PODO447, that recognizes a glycoepitope on Podxl expressed at high levels by a variety of tumors including the majority of life-threatening high-grade serous ovarian tumors. Thus, tumor-restricted PODO447 exhibits the appropriate specificity for further development as a targeted immunotherapy.
Is rheumatoid arthritis a risk factor for acute coronary syndrome also among individuals at elevated risk, such as individuals presenting with acute chest pain?
Authors: Svensson Per , Bergstrom Miriam , Discacciati Andrea , Ljung Lina , Jernberg Tomas , Frick Mats , Linder Rickard , Askling Johan
Published: November 2020

Background

Patients with rheumatoid arthritis (RA) are, on average, at increased risk of acute coronary syndrome (ACS) compared to the general population, but it remains unknown whether RA remains an ACS risk factor also in settings where the ACS risk is already high elevated, such as among individuals presenting to the emergency department (ED) with chest pain.

Methods and results

We included 49 283 individuals (514 (1.0%) had RA) presenting with chest pain at the four hospital EDs in Stockholm, Sweden, 2013–2016 in a cohort study. Information on exposure (RA), outcome (ACS) and comorbidities was provided through national registers. The association between RA and ACS was assessed, overall and by levels of high-sensitivity cardiac troponin T (hs-cTnT) and number of ACS risk factors, using logistic regression models adjusted for age, sex, hospital, calendar year and cardiovascular risk factors. ACS was more common in patients with (8.2%) than without (4.6%) RA, adjusted OR =1.4, 95% CI 1.0 to 2.0. This association was particularly strong in individuals with initial hs-cTnT levels between 5 and 14 ng/L, or no additional ACS risk factors (adjusted ORs above 2), but no longer detectable in those with hs-cTnT >14 ng/L or with three or more additional ACS risk factors.

Conclusion

RA is a risk factor for ACS also among patients at the ED with chest pain. This association is not explained by traditional ACS risk factors, and most pronounced in patients with normal hs-cTnT and few other ACS risk factors, prompting particular ACS vigilance in this RA patient group.