bluuebunny/crossref_metadata_2025 huggingface dataset:
Making an impact on kidney disease in people with type 2 diabetes: the importance of screening for albuminuria
Authors: McGill Janet B , Haller Hermann , Roy-Chaudhury Prabir , Cherrington Andrea , Wada Takashi , Wanner Christoph , Ji Linong , Rossing Peter
Published: July 2022

Albuminuria is useful for early screening and diagnosis of kidney impairment, especially in people with pre-diabetes or type 2 diabetes (T2D), which is the leading cause of chronic kidney disease (CKD) and end-stage kidney disease (ESKD), associated with increased mortality, poor cardiovascular outcomes, and high economic burden. Identifying patients with CKD who are most likely to progress to ESKD permits timely implementation of appropriate interventions. The early stages of CKD are asymptomatic, which means identification of CKD relies on routine assessment of kidney damage and function. Both albuminuria and estimated glomerular filtration rate are measures of kidney function. This review discusses albuminuria as a marker of kidney damage and cardiorenal risk, highlights the importance of early screening and routine testing for albuminuria in people with T2D, and provides new insights on the optimum management of CKD in T2D using albuminuria as a target in a proposed algorithm. Elevated urine albumin can be used to detect CKD in people with T2D and monitor its progression; however, obstacles preventing early detection exist, including lack of awareness of CKD in the general population, poor adherence to clinical guidelines, and country-level variations in screening and treatment incentives. With albuminuria being used as an entry criterion and a surrogate endpoint for kidney failure in clinical trials, and with novel treatment interventions available to prevent CKD progression, there is an urgent need for early screening and diagnosis of kidney function decline in people with T2D or pre-diabetes.
In-hospital hyperglycemia but not diabetes mellitus alone is associated with increased in-hospital mortality in community-acquired pneumonia (CAP): a systematic review and meta-analysis of observational studies prior to COVID-19
Authors: Barmanray Rahul D , Cheuk Nathan , Fourlanos Spiros , Greenberg Peter B , Colman Peter G , Worth Leon J
Published: July 2022

The objective of this review was to quantify the association between diabetes, hyperglycemia, and outcomes in patients hospitalized for community-acquired pneumonia (CAP) prior to the COVID-19 pandemic by conducting a systematic review and meta-analysis. Two investigators independently screened records identified in the PubMed (MEDLINE), EMBASE, CINAHL, and Web of Science databases. Cohort and case–control studies quantitatively evaluating associations between diabetes and in-hospital hyperglycemia with outcomes in adults admitted to hospital with CAP were included. Quality was assessed using the Newcastle-Ottawa Quality Assessment Scale, effect size using random-effects models, and heterogeneity using I2statistics. Thirty-eight studies met the inclusion criteria. Hyperglycemia was associated with in-hospital mortality (adjusted OR 1.28, 95% CI 1.09 to 1.50) and intensive care unit (ICU) admission (crude OR 1.82, 95% CI 1.17 to 2.84). There was no association between diabetes status and in-hospital mortality (adjusted OR 1.04, 95% CI 0.72 to 1.51), 30-day mortality (adjusted OR 1.13, 95% CI 0.77 to 1.67), or ICU admission (crude OR 1.91, 95% CI 0.74 to 4.95). Diabetes was associated with increased mortality in all studies reporting >90-day postdischarge mortality and with longer length of stay only for studies reporting crude (OR 1.50, 95% CI 1.11 to 2.01) results. In adults hospitalized with CAP, in-hospital hyperglycemia but not diabetes alone is associated with increased in-hospital mortality and ICU admission. Diabetes status is associated with increased >90-day postdischarge mortality. Implications for management are that in-hospital hyperglycemia carries a greater risk for in-hospital morbidity and mortality than diabetes alone in patients admitted with non-COVID-19 CAP. Evaluation of strategies enabling timely and effective management of in-hospital hyperglycemia in CAP is warranted.
Appendectomy and risk for inflammatory bowel disease: effect of age and time post appendectomy – a cohort study
Authors: Fantodji Canisius , Jantchou Prévost , Parent Marie-Elise , Rousseau Marie-Claude
Published: July 2022

Background and objective

Appendectomy may modulate the risk of inflammatory bowel disease through an effect on the gut microbiota. This study investigated the associations between appendectomy and incidence of Crohn’s disease (CD) or ulcerative colitis (UC), with an emphasis on the influence of age and time post appendectomy.

Methods

This cohort study included 400 520 subjects born in Québec in 1970–1974 and followed until 2014. Administrative health data were used to ascertain appendectomy and cases of CD and UC. Cox proportional hazards models with time-dependent variables (appendectomy and time elapsed post appendectomy) allowed for the estimation of HRs and 95% CIs.

Results

A total of 2545 (0.6%) CD cases and 1134 (0.3%) UC cases were identified during follow-up. Appendectomy increased the risk of CD (HR=2.02; 95% CI: 1.66 to 2.44), especially when performed at 18–29 years of age. The risk of CD was increased in the first 2 years, and decreased significantly after ≥15 years post appendectomy. Appendectomy appeared to protect against UC (HR=0.39; 95% CI: 0.22 to 0.71). The risk of UC was not associated with age at appendectomy, but decreased with time elapsed post appendectomy (HR=0.21; 95% CI: 0.06 to 0.72, comparing ≥5 with 0–4 years after appendectomy).

Conclusions

The increased risk of CD related to appendectomy in young adults may result from detection bias, but physicians should have a low threshold for suspicion of CD in young symptomatic adults with a history of appendectomy. A strong protective effect of appendectomy against UC was observed after 5 years.
Crowdfunding for health research: a qualitative evidence synthesis and a pilot programme
Authors: Kpokiri Eneyi Edith , Sri-Pathmanathan Clarisse , Shrestha Priyanka , Navaid Sana , Wiwatpanit Teerawat , Wijegunawardana Asha , Ali Umar Mahmud , Jackson Debra , Alger Jackeline , Bohren Meghan A , Hoole Mia , Labarda Meredith , Juban Noel , Launois Pascal , Tang Weiming , Halpaap Beatrice , Tucker Joseph D
Published: July 2022

Background

Many low-income and middle-income country (LMIC) researchers have disadvantages when applying for research grants. Crowdfunding may help LMIC researchers to fund their research. Crowdfunding organises large groups of people to make small contributions to support a research study. This manuscript synthesises global qualitative evidence and describes a Special Programme for Research and Training in Tropical Diseases (TDR) crowdfunding pilot for LMIC researchers.

Methods

Our global systematic review and qualitative evidence synthesis searched six databases for qualitative data. We used a thematic synthesis approach and assessed our findings using the GRADE-CERQual approach. Building on the review findings, we organised a crowdfunding pilot to support LMIC researchers and use crowdfunding. The pilot provided an opportunity to assess the feasibility of crowdfunding for infectious diseases of poverty research in resource-constrained settings.

Results

Nine studies were included in the qualitative evidence synthesis. We identified seven findings which we organised into three broad domains: public engagement strategies, correlates of crowdfunding success and risks and mitigation strategies. Our pilot data suggest that crowdfunding is feasible in diverse LMIC settings. Three researchers launched crowdfunding campaigns, met their goals and received substantial monetary (raising a total of US$26 546 across all three campaigns) and non-monetary contributions. Two researchers are still preparing for the campaign launch due to COVID-19-related difficulties.

Conclusion

Public engagement provides a foundation for effective crowdfunding for health research. Our evidence synthesis and pilot data provide practical strategies for LMIC researchers to engage the public and use crowdfunding. A practical guide was created to facilitate these activities across multiple settings.
Enigma of the cholesterol paradox in acute myocardial infarction: lessons from an 8-year follow-up of all-cause mortality in an age-matched and sex-matched case–control study with controls from the patients’ recruitment area
Authors: Nilsson Göran , Leppert Jerzy , Ohrvik John
Published: July 2022

Objective

To assess the impact of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) on long-term all-cause mortality (ACM) in patients with acute myocardial infarction (AMI) and controls.

Design

Matched case–control study with 8-year follow-up.

Setting

Vastmanland County Hospital, Vasteras, Sweden.

Participants

Consecutive patients with AMI admitted to the coronary care unit from March 2005 to May 2010 and age-matched and sex-matched controls from the general population.

Outcome measures

ACM.

Results

Person-year at risk among patients with AMI and controls was 11 667 (cases: 5780 and controls: 5887). During follow-up, 199 patients and 84 controls died, implying 3.4 deaths among patients and 1.4 among controls per 100 person-years at risk. Unadjusted Cox analyses showed significantly increasing mortality by decreasing TC and LDL-C levels in both patients (HR=0.70, 95% CI 0.62 to 0.79, p<0.001, and HR=0.64, 95% CI 0.56 to 0.74, p<0.001) and controls (HR=0.73, 95% CI 0.60 to 0.89, p=0.002, and HR=0.74, 95% CI 0.59 to 0.93, p=0.010). After adjusting for clinical variables, the results for the patients remained significant. Cox analyses of the relations between mortality and TC and LDL-C below and above their respective medians revealed the following pattern. Patients: below medians were TC and LDL-C levels significantly inversely related to mortality; above medians there were no relations with mortality. Controls: below medians were TC and LDL-C levels significantly inversely related to mortality; above medians were LDL-C levels significantly positively related to mortality. Mean LDL-C level in patients with blood sampled >12 hours after symptom onset was 0.41 mmol/L lower than that in patients with blood sampled ≤12 hours (p=0.030). This LDL-C decrease was reasonably caused by ongoing AMI and reflects the difference in LDL-C levels between patients and controls.

Conclusions

In patients with AMI, lower TC and LDL-C levels independently predict higher ACM. In their controls, LDL-C levels above the median independently predict higher ACM. This study adds to the body of evidence supporting the existence of a cholesterol paradox.
Development and validation of a clinical prediction model of acute kidney injury in intensive care unit patients at a rural tertiary teaching hospital in South Africa: a study protocol
Authors: Mrara Busisiwe , Paruk Fathima , Sewani-Rusike Constance , Oladimeji Olanrewaju
Published: July 2022

Introduction

Acute kidney injury (AKI) is a decline in renal function lasting hours to days. The rising global incidence of AKI, and associated costs of renal replacement therapy, is a public health priority. With the only therapeutic option being supportive therapy, prevention and early diagnosis will facilitate timely interventions to prevent progression to chronic kidney disease. While many factors have been identified as predictive of AKI, none have shown adequate sensitivity or specificity on their own. Many tools have been developed in developed-country cohorts with higher rates of non-communicable disease, and few have been validated and practically implemented. The development and validation of a predictive tool incorporating clinical, biochemical and imaging parameters, as well as quantification of their impact on the development of AKI, should make timely and improved prediction of AKI possible. This study is positioned to develop and validate an AKI prediction tool in critically ill patients at a rural tertiary hospital in South Africa.

Method and analysis

Critically ill patients will be followed from admission until discharge or death. Risk factors for AKI will be identified and their impact quantified using statistical modelling. Internal validation of the developed model will be done on separate patients admitted at a different time. Furthermore, patients developing AKI will be monitored for 3 months to assess renal recovery and quality of life. The study will also explore the utility of endothelial monitoring using the biomarker Syndecan-1 and capillary leak measurements in predicting persistent AKI.

Ethics and dissemination

The study has been approved by the Walter Sisulu University Faculty of Health Science Research Ethics and Biosafety Committee (WSU No. 005/2021), and the Eastern Cape Department of Health Research Ethics (approval number: EC 202103006). The findings will be shared with facility management, and presented at relevant conferences and seminars.
Role of the regulator in enabling a just culture: a qualitative study in mental health and hospital care
Authors: Weenink Jan-Willem , Wallenburg Iris , Hartman Laura , van Baarle Eva , Leistikow Ian , Widdershoven Guy , Bal Roland
Published: July 2022

Objectives

A just culture is considered a promising way to improve patient safety and working conditions in the healthcare sector, and as such is also of relevance to healthcare regulators who are tasked with monitoring and overseeing quality and safety of care. The objective of the current study is to explore the experiences in healthcare organisations regarding the role of the healthcare inspectorate in enabling a just culture.

Design

Qualitative study using interviews and focus groups that were transcribed verbatim, and observations of which written reports were made. Transcripts and observation reports were thematically analysed.

Setting

Three mental healthcare providers, two hospitals and the healthcare inspectorate in the Netherlands.

Participants

We conducted 61 interviews and 7 focus groups with healthcare professionals, managers and other staff in healthcare organisations and with inspectors. Additionally, 27 observations were conducted in healthcare organisations.

Results

We identified three themes in our data. First, professionals and managers in healthcare organisations perceive the inspectorate as a potential catalyst for learning processes, for example, as an instigator of investigating incidents thoroughly, yet also as a potential barrier as its presence and procedures limit how open employees feel they can be. Second, a just culture is considered relational and layered, meaning that relationships between different layers within or outside the organisation might hinder or promote a just culture. Finally, for inspectors to enable a just culture requires finding a balance between allowing organisations the time to take responsibility for quality and safety issues, and timely regulatory intervention when healthcare providers are unwilling or unable to act.

Conclusions

If regulators intend to enable the development of a just culture within healthcare organisations, they must adopt regulatory procedures that support reflection and learning within the organisations they regulate and consider mutual trust as a vital regulatory tool.
Towards consensus: defining and supporting a professional role for pharmacists associated with traditional and complementary medicines – a protocol of implementing an international e-survey
Authors: Harnett Joanna E , Desselle Shane , Ung Carolina Oi Lam
Published: July 2022

Introduction

Traditional and complementary medicines (T&CM) are predominantly self-selected from retail outlets including pharmacies as part of self-care practices. Concerns about the appropriate and safe use of T&CM products raises questions about ‘should’ and ‘how’ pharmacists could adopt professional responsibilities. There lacks a consensus about the scope of these responsibilities, or the initiatives required to execute them. The aim of this study is to identify an international set of core responsibilities that support pharmacists’ contribution to ensuring the quality and safe use of T&CMs to promote public health.

Methods and analysis

An international cross-sectional e-survey of pharmacists representing the six WHO regions will be conducted over a 12-month period. Pharmacists will be invited via representative organisations and professional networks within their respective country. Survey responses to statements about the relevance of T&CM to day-to-day practice; opinions about the bioethical and practice responsibilities; and support required to build their scope of practice associated with T&CM will be collected centrally via the online survey platform Survey Monkey and analysed using the Statistical Package for Social Sciences V.27 software for Windows. Bivariate statistical analysis will be conducted to examine the associations between agreement to statements within each section with key demographic variables, country of practice, pharmacy type, age, gender, qualification and years in practice. Cronbach’s alpha will be used to test the internal consistency of items from certain sections of the survey and evince their clarity to respondents of the questionnaire.

Ethics and dissemination

Ethics approval has been obtained from the University of Macau (approval number SSHRE21-APP068-ICMS-01). The results of this survey will be used to inform key discussion points in a consensus process and a step towards developing an agreed and defined professional role for pharmacists in T&CMs.
Effectiveness of a family customised online FOCUS programme aimed on building resiliency in dyad relationship to support dyadic illness management in persons with heart failure and their informal caregiver: a randomised clinical trial protocol
Authors: Yang Weiling , Cao Yongjun , Li Yanting , Zhang Xiaonan , Li Xuedong , Jiang Sixuan , LV Qingyun , Cheng Mei , Zhang Xin , Zang Xiaoying
Published: July 2022

Introduction

Living with heart failure (HF), is a shared journey and arduous work for patients and their informal family caregivers. Given the key role and limited evidence of dyad illness management in improving dyad health in the context of HF, we developed a customisable, relationship focused, family online dynamic disease management programme—FOCUS programme—to improve dyad health for HF patients and their informal caregivers in China.

Methods and analysis

Based on the Theory of Dyadic Illness Management and the Systemic Transactional Model of Stress and Coping, the family customised online FOCUS programme has five modules: (1) family participatory; (2) open communication; (3) coping effectiveness; (4) uncertainty reduction and 5) shared dyad life stories. HF family dyads will be recruited in the cardiology wards of four university-affiliated hospitals in China. The dyads (N=142) will be randomly allocated to the intervention group that will receive the family customised online FOCUS programme, and the attention control group that will not receive elements of the FOCUS programme. Dyadic coping, HF somatic perception, self-care, anxiety and depression for patients and family caregivers and all-cause mortality and hospital admission for patients will be measured at baseline, 4 weeks (after the discharge, T1), 12 weeks (after the discharge, T2) and 24 weeks (after the discharge, T3). Statistical analysis will be performed using SPSS V. 22.0 software.

Ethics and dissemination

The study protocol was approved by the ethics committees of Tianjin Medical University (Reference number TMUHEC2019002) that covers all the centres enrolled in this study. The findings of this study will be published in scientific journals and will be presented at scientific conferences.

Trial registration number

ChiCTR2100053168.
Multilevel analysis of quality of antenatal care and associated factors among pregnant women in Ethiopia: a community based cross-sectional study
Authors: Negash Wubshet Debebe , Fetene Samrawit Mihret , Shewarega Ever Siyoum , Fentie Elsa Awoke , Asmamaw Desale Bihonegn , Teklu Rediet Eristu , Aragaw Fantu Mamo , Belay Daniel Gashaneh , Alemu Tewodros Getaneh , Eshetu Habitu Birhan
Published: July 2022

Objective

To determine the magnitude of quality of antenatal care and associated factors among pregnant women in Ethiopia.

Design

A community-based cross-sectional study.

Setting

Ethiopia.

Participants

A total of 4757 weighted sample of pregnant women from 18 January 2016 to 27 June 2016, were included for this analysis.

Outcome

Quality of antenatal care (ANC).

Methods

Our analysis was based on secondary data using the 2016 Ethiopian Demographic and Health Survey. The quality of ANC was measured when all six essential components, such as blood pressure measurements, blood tests, urine tests, nutrition counselling, birth preparation advice during pregnancy and information on potential complications, were provided. Stata V.14 software was used for analysis. A multilevel mixed-effect logistic regression analysis was fitted. Adjusted OR (AOR) with 95% CIs was used to show the strength and direction of the association. Statistical significance was declared at a p value less than 0.05.

Results

The magnitude of quality of ANC in Ethiopia was 22.48% (95% CI: 21.31% to 23.69%). Educational status; primary (AOR=1.34; 95% CI: 1.06 to 1.68) and secondary (AOR=2.46; 95% CI: 1.76 to 3.45), middle (AOR=1.31; 95% CI: 1.01 to 1.72) and rich (AOR=2.08; 95% CI: 1.59 to 2.72) wealth status, being married (AOR=2.34; 95% CI: 1.08 to 5.10) and four or more ANC (AOR=2.01; 95% CI: 1.67 to 2.40) were statistically significant associated factors of quality ANC in Ethiopia.

Conclusions

This study found that nearly only one in five pregnant women received quality ANC during pregnancy. To improve the quality of ANC in Ethiopia, Ministry of Health and health facilities are needed to increase financial support strategies that enable pregnant women from poor households to use health services and enhance pregnant women’s understanding of the significance of quality of ANC through health education. Additionally, Community health workers should also be placed on supporting unmarried pregnant women to have quality ANC.
Operating room relay strategy for turnover time improvement: a quality improvement project
Authors: Riveros Perez Efrain , Kerko Rebecca , Lever Nathaniel , White Abigail , Kahf Sebastian , Avella-Molano Bibiana
Published: July 2022

Introduction

Operating room (OR) management plays a pivotal role in the healthcare system due to the high cash flow it yields. Enhancing communication in the OR, which is the common root problem for delays, might improve OR efficiency and revenues for healthcare. This study aims to evaluate the impact of an OR relay strategy on turnover time (TOT).

Methods

A quality improvement project was conducted. In the intervention group, a certified registered nurse anaesthetist (CRNA) remained outside of the OR, coordinating the steps to get the next patient ready. This CRNA communicated with the anaesthesia providers within the OR via a Microsoft Team chat. The TOT for the control group was recorded from the electronic anaesthesia record system.

Results/data analysis

Analysis of 636 turnovers was performed with non-parametric tests. The OR relay strategy decreased TOT for most ORs, with statistically significant results for three of the ORs and the overall ORs system. A decreased in variability between TOTs was evidenced for the overall OR and the majority of the ORs evaluated individually.

Conclusion

The OR relay strategy has a positive impact on TOT.
Regional single-queue scheduling platform for specialist diagnostics in the lung cancer pathway: accelerating cancer recovery from the COVID-19 pandemic
Authors: Evison Matthew , Shackley David , Galligan-Dawson Lisa
Published: July 2022

Lung cancer is the single biggest cause of cancer death. The diagnostic pathway can be complex, including specialist cancer diagnostics that are not performed at every hospital. One such example is endobronchial ultrasound (EBUS), a day-case bronchoscopic procedure used for nodal staging and tissue diagnosis. In this proof-of-concept pilot in Greater Manchester, we tested a novel digital EBUS booking platform. This platform was accessible across multiple acute care trusts and provided visibility of all available EBUS appointments, allowing referring teams to book directly into the appropriate slot. During a 6-month pilot, 193 EBUS procedures were booked through this new single-queue platform. The median waiting times reduced by 2 days from 9 to 7 days (22% reduction and saving approximately 386 days in total) and reduced variation in waiting times by 1 day from 5 to 4 days (20% reduction). 98% of patients who completed an experience of care survey felt the process was ‘very well’ or ‘well’ organised and 77% felt the most important factor in deciding where to have their EBUS was the earliest possible appointment regardless of travel. This proof-of-concept pilot has shown improvements in cancer waiting times with significant future potential in delivering specialist cancer diagnostics.
SARS-CoV-2 infections and attitudes towards COVID-19 vaccines among healthcare workers in the New York Metropolitan area, USA
Authors: Agaku Israel T , Dimaggio Alisa , Fishelov Avigal , Brathwaite Alianne , Ahmed Saief , Malinowski Michelle , Long Theodore
Published: July 2022

Objective

Because of their increased interaction with patients, healthcare workers (HCWs) face greater vulnerability to COVID-19 exposure than the general population. We examined prevalence and correlates of ever COVID-19 diagnosis and vaccine uncertainty among HCWs.

Design

Cross-sectional data from the Household Pulse Survey (HPS) conducted during July to October 2021.

Setting

HPS is designed to yield representative estimates of the US population aged ≥18 years nationally, by state and across selected metropolitan areas.

Participants

Our primary analytical sample was adult HCWs in the New York Metropolitan area (n=555), with HCWs defined as individuals who reported working in a ‘Hospital’; ‘Nursing and residential healthcare facility’; ‘Pharmacy’ or ‘Ambulatory healthcare setting’. In the entire national sample, n=25 909 HCWs completed the survey. Descriptive analyses were performed with HCW data from the New York Metropolitan area, the original epicentre of the pandemic. Multivariable logistic regression analyses were performed on pooled national HCW data to explore how HCW COVID-19-related experiences, perceptions and behaviours varied as a function of broader geographic, clinical and sociodemographic characteristics.

Results

Of HCWs surveyed in the New York Metropolitan area, 92.3% reported being fully vaccinated, and 20.9% had ever been diagnosed of COVID-19. Of the subset of HCWs in the New York Metropolitan area not yet fully vaccinated, 41.8% were vaccine unsure, 4.5% planned to get vaccinated for the first time soon, 1.6% had got their first dose but were not planning to receive the remaining dose, while 52.1% had got their first dose and planned to receive the remaining dose. Within pooled multivariable analysis of the national HCW sample, personnel in nursing/residential facilities were less likely to be fully vaccinated (adjusted OR, AOR 0.79, 95% CI 0.63 to 0.98) and more likely to report ever COVID-19 diagnosis (AOR 1.35, 95% CI 1.13 to 1.62), than those working in hospitals. Of HCWs not yet vaccinated nationally, vaccine-unsure individuals were more likely to be White and work in pharmacies, whereas vaccine-accepting individuals were more likely to be employed by non-profit organisations and work in ambulatory care facilities. Virtually no HCW was outrightly vaccine-averse, only unsure.

Conclusions

Differences in vaccination coverage existed by individual HCW characteristics and healthcare operational settings. Targeted efforts are needed to increase vaccination coverage.
Nationwide gastric cancer prevention in China, 2021–2035: a decision analysis on effect, affordability and cost-effectiveness optimisation
Authors: Wang Zixing , Han Wei , Xue Fang , Zhao Yujie , Wu Peng , Chen Yali , Yang Cuihong , Gu Wentao , Jiang Jingmei
Published: July 2022

Objective

To project future trajectories of the gastric cancer (GC) burden in China under different scenarios of GC prevention and identify strategies to improve affordability and cost-effectiveness.

Design

Using a cohort of Chinese men and women born during 1951–1980, we assumed that different prevention strategies were conducted, including eradication ofHelicobacter pylori(Hp) and endoscopy screening (one-time, annual, biennial, triennial or stratified according to personal risk). We performed a literature search to identify up-to-date data and populate a Markov model to project the number of new GC cases and deaths during 2021–2035, as well as resource requirements and quality-adjusted life-years (QALYs). We examined the impacts of general (among the whole population) and targeted (high-risk population) prevention.

Results

During 2021–2035, 10.0 million new GC cases and 5.6 million GC deaths would occur, with 7.6%–35.5% and 6.9%–44.5%, respectively, being avoidable through various prevention strategies. Relative to the status quo, Hp eradication was a cost-saving strategy. General annual screening dominated other screening strategies, but cost more than CNY 70 000 per QALY gained (willingness-to-pay) compared with Hp eradication. Among endoscopy strategies, targeted screening resulted in 44%–49% lower cost per QALY gained over the status quo than general screening. Among high-risk population, tailoring the screening frequency according to personal risk could reduce endoscopy-related resources by 22% compared with biennial screening and by 55% compared with annual screening,

Conclusion

Our findings provide important input for future decision-making and investment, highlighting the need and feasibility for China to include GC prevention in its national health plans.
Vaccine escape, increased breakthrough and reinfection in infliximab-treated patients with IBD during the Omicron wave of the SARS-CoV-2 pandemic
Authors: Kennedy Nicholas A , Janjua Malik , Chanchlani Neil , Lin Simeng , Bewshea Claire , Nice Rachel , McDonald Timothy J , Auckland Cressida , Harries Lorna W , Davies Merlin , Michell Stephen , Kok Klaartje B , Lamb Christopher A , Smith Philip J , Hart Ailsa L , Pollok Richard CG , Lees Charlie W , Boyton Rosemary J , Altmann Daniel M , Sebastian Shaji , Powell Nicholas , Goodhand James R , Ahmad Tariq
Published: July 2022

Objective

Antitumour necrosis factor (TNF) drugs impair serological responses following SARS-CoV-2 vaccination. We sought to assess if a third dose of a messenger RNA (mRNA)-based vaccine substantially boosted anti-SARS-CoV-2 antibody responses and protective immunity in infliximab-treated patients with IBD.

Design

Third dose vaccine induced anti-SARS-CoV-2 spike (anti-S) receptor-binding domain (RBD) antibody responses, breakthrough SARS-CoV-2 infection, reinfection and persistent oropharyngeal carriage in patients with IBD treated with infliximab were compared with a reference cohort treated with vedolizumab from the impaCt of bioLogic therApy on saRs-cov-2 Infection and immuniTY (CLARITY) IBD study.

Results

Geometric mean (SD) anti-S RBD antibody concentrations increased in both groups following a third dose of an mRNA-based vaccine. However, concentrations were lower in patients treated with infliximab than vedolizumab, irrespective of whether their first two primary vaccine doses were ChAdOx1 nCoV-19 (1856 U/mL (5.2) vs 10 728 U/mL (3.1), p<0.0001) or BNT162b2 vaccines (2164 U/mL (4.1) vs 15 116 U/mL (3.4), p<0.0001). However, no differences in anti-S RBD antibody concentrations were seen following third and fourth doses of an mRNA-based vaccine, irrespective of the combination of primary vaccinations received. Post-third dose, anti-S RBD antibody half-life estimates were shorter in infliximab-treated than vedolizumab-treated patients (37.0 days (95% CI 35.6 to 38.6) vs 52.0 days (95% CI 49.0 to 55.4), p<0.0001).

Compared with vedolizumab-treated, infliximab-treated patients were more likely to experience SARS-CoV-2 breakthrough infection (HR 2.23 (95% CI 1.46 to 3.38), p=0.00018) and reinfection (HR 2.10 (95% CI 1.31 to 3.35), p=0.0019), but this effect was uncoupled from third vaccine dose anti-S RBD antibody concentrations. Reinfection occurred predominantly during the Omicron wave and was predicted by SARS-CoV-2 antinucleocapsid concentrations after the initial infection. We did not observe persistent oropharyngeal carriage of SARS-CoV-2. Hospitalisations and deaths were uncommon in both groups.

Conclusions

Following a third dose of an mRNA-based vaccine, infliximab was associated with attenuated serological responses and more SARS-CoV-2 breakthrough infection and reinfection which were not predicted by the magnitude of anti-S RBD responses, indicative of vaccine escape by the Omicron variant.

Trial registration number

ISRCTN45176516.
Long-term outcomes in distinct phenogroups of patients with primary mitral regurgitation undergoing valve surgery
Authors: Kwak Soongu , Lee Seung-Ah , Lim Jaehyun , Yang Seokhun , Choi Hong-Mi , Hwang In-Chang , Lee Sahmin , Yoon Yeonyee Elizabeth , Park Jun-Bean , Kim Hyung-Kwan , Kim Yong-Jin , Song Jong-Min , Cho Goo-Yeong , Kim Kyung-Hwan , Kang Duk-Hyun , Kim Dae-Hee , Lee Seung-Pyo
Published: July 2022

Objectives

Patients with mitral regurgitation (MR) may be heterogeneous with different risk profiles. We aimed to identify distinct phenogroups of patients with severe primary MR and investigate their long-term prognosis after mitral valve (MV) surgery.

Methods

The retrospective cohort of patients with severe primary MR undergoing MV surgery (derivation, n=1629; validation, n=692) was analysed. Latent class analysis was used to classify patients into subgroups using 15 variables. The primary outcome was all-cause mortality after MV surgery.

Results

During follow-up (median 6.0 years), 149 patients (9.1%) died in the derivation cohort. In the univariable Cox analysis, age, female, atrial fibrillation, left ventricular (LV) end-systolic dimension/volumes, LV ejection fraction, left atrial dimension and tricuspid regurgitation peak velocity were significant predictors of mortality following MV surgery. Five distinct phenogroups were identified, three younger groups (group 1–3) and two older groups (group 4–5): group 1, least comorbidities; group 2, men with LV enlargement; group 3, predominantly women with rheumatic MR; group 4, low-risk older patients; and group 5, high-risk older patients. Cumulative survival was the lowest in group 5, followed by groups 3 and 4 (5-year survival for groups 1–5: 98.5%, 96.0%, 91.7%, 95.6% and 83.4%; p<0.001). Phenogroups had similar predictive performance compared with the Mitral Regurgitation International Database score in patients with degenerative MR (3-year C-index, 0.763 vs 0.750, p=0.602). These findings were reproduced in the validation cohort.

Conclusion

Five phenogroups of patients with severe primary MR with different risk profiles and outcomes were identified. This phenogrouping strategy may improve risk stratification when optimising the timing and type of interventions for severe MR.
Completeness and representativeness of small area socioeconomic data linked with the UK Clinical Practice Research Datalink (CPRD)
Authors: Mahadevan Preveina , Harley Mia , Fordyce Stuart , Hodgson Susan , Ghosh Rebecca , Myles Puja , Booth Helen , Axson Eleanor
Published: July 2022

Background

The Clinical Practice Research Datalink (CPRD) holds primary care electronic healthcare records for 25% of the UK population. CPRD data can be linked via practice postcode in the UK, and additionally via patient postcode in England, to area-level socioeconomic status (SES) data including the Index of Multiple Deprivation (IMD), the Carstairs Index and the Townsend Deprivation Index; as well as rural–urban classification (RUC). This study aims to describe the completeness and representativeness of CPRD-linked SES and RUC data.

Methods

Patients currently registered at general practices contributing data to the May 2021 snapshots of CPRD GOLD (n=445 587) and CPRD Aurum (n=13 278 825) were used to assess the completeness and representativeness of CPRD-linked SES and RUC data against the UK general population.

Results

All currently registered patients had complete SES and RUC data at practice level across the UK. Most English patients in CPRD GOLD (78%), CPRD Aurum (94%) and combined (93%) had SES and RUC data at patient level. Patient-level SES data in CPRD for England were comparable to England’s general population (average IMD decile in CPRD 5.52±0.00 vs 5.50±0.02). CPRD UK practices were on average in more deprived areas than the UK general population (6.06±0.07 vs 5.50±0.02). A slightly higher proportion of CPRD patients and practices were from urban areas (85%) as compared with the UK general population (82%).

Conclusion

Completeness of CPRD-linked SES and RUC data is high. The CPRD populations were broadly representative of the general populations in the UK in terms of SES and RUC.
Reshaping the tumor microenvironment with oncolytic viruses, positive regulation of the immune synapse, and blockade of the immunosuppressive oncometabolic circuitry
Authors: Nguyen Teresa T , Shin Dong Ho , Sohoni Sagar , Singh Sanjay K , Rivera-Molina Yisel , Jiang Hong , Fan Xuejun , Gumin Joy , Lang Frederick F , Alvarez-Breckenridge Christopher , Godoy-Vitorino Filipa , Zhu Lisha , Zheng W Jim , Zhai Lijie , Ladomersky Erik , Lauing Kristen L , Alonso Marta M , Wainwright Derek A , Gomez-Manzano Candelaria , Fueyo Juan
Published: July 2022

Background

Oncolytic viruses are considered part of immunotherapy and have shown promise in preclinical experiments and clinical trials. Results from these studies have suggested that tumor microenvironment remodeling is required to achieve an effective response in solid tumors. Here, we assess the extent to which targeting specific mechanisms underlying the immunosuppressive tumor microenvironment optimizes viroimmunotherapy.

Methods

We used RNA-seq analyses to analyze the transcriptome, and validated the results using Q-PCR, flow cytometry, and immunofluorescence. Viral activity was analyzed by replication assays and viral titration. Kyn and Trp metabolite levels were quantified using liquid chromatography–mass spectrometry. Aryl hydrocarbon receptor (AhR) activation was analyzed by examination of promoter activity. Therapeutic efficacy was assessed by tumor histopathology and survival in syngeneic murine models of gliomas, including Indoleamine 2,3-dioxygenase (IDO)-/- mice. Flow cytometry was used for immunophenotyping and quantification of cell populations. Immune activation was examined in co-cultures of immune and cancer cells. T-cell depletion was used to identify the role played by specific cell populations. Rechallenge experiments were performed to identify the development of anti-tumor memory.

Results

Bulk RNA-seq analyses showed the activation of the immunosuppressive IDO-kynurenine-AhR circuitry in response to Delta-24-RGDOX infection of tumors. To overcome the effect of this pivotal pathway, we combined Delta-24-RGDOX with clinically relevant IDO inhibitors. The combination therapy increased the frequency of CD8+T cells and decreased the rate of myeloid-derived suppressor cell and immunosupressive Treg tumor populations in animal models of solid tumors. Functional studies demonstrated that IDO-blockade-dependent activation of immune cells against tumor antigens could be reversed by the oncometabolite kynurenine. The concurrent targeting of the effectors and suppressors of the tumor immune landscape significantly prolonged the survival in animal models of orthotopic gliomas.

Conclusions

Our data identified for the first time thein vivorole of IDO-dependent immunosuppressive pathways in the resistance of solid tumors to oncolytic adenoviruses. Specifically, the IDO-Kyn-AhR activity was responsible for the resurface of local immunosuppression and resistance to therapy, which was ablated through IDO inhibition. Our data indicate that combined molecular and immune therapy may improve outcomes in human gliomas and other cancers treated with virotherapy.
We want to help: ethical challenges of medical migration and brain waste during a pandemic
Authors: Fenton Elizabeth , Chillag Kata
Published: July 2022

Health worker shortages in many countries are reaching crisis levels, exacerbated by factors associated with the COVID-19 pandemic. In New Zealand, the medical specialists union has called for a health workforce emergency to be declared, yet at the same time, many foreign-trained healthcare workers are unable to stay in the country or unable to work. While their health systems differ, countries such as New Zealand, the USA and the UK at least partially rely on international medical graduates (IMGs) to ensure access to health services, particularly in underserved communities. This paper focuses on the challenges faced by many IMGs, particularly those that constrain their capacity to live and work in the countries that rely on their skills. These challenges give rise to two ethical problems. First, they represent a failure of reciprocity towards IMGs; second, they represent a source of harm, both to IMGs themselves and to communities whose healthcare service depends on contributions made by IMGs. We argue that brain waste and disvaluing the contributions of IMGs and other foreign-trained health professionals have significant costs for maintaining a functional healthcare system, costs which must be adequately recognised and counted.
Application of optical coherence tomography in decision-making of post-thrombectomy adjunctive treatments
Authors: Li Di , Tang Tao , Hu Teng , Walczak Piotr , Gandhi Dheeraj , Li Shen
Published: July 2022

An adult patient with acute basilar artery occlusion underwent mechanical thrombectomy. After complete reperfusion, a 70% residual stenosis of the proximal basilar artery was observed. Intravascular optical coherence tomography (OCT) identified lipid plaques with an intact fibrous cap and thrombus in the culprit lesion, indicating plaque erosion was the mechanism of in situ thrombosis. Adjunctive antiplatelet therapy rather than rescue interventions was pursued for its beneficial effects in acute coronary syndrome caused by plaque erosion. The patient had a 90-day modified Rankin Scale score of 0. OCT enables precise evaluation of vessel characteristics following thrombectomy, so may improve outcomes through subsequent tailored treatments.
Genotype–phenotype correlations in valosin-containing protein disease: a retrospective muticentre study
Authors: Schiava Marianela , Ikenaga Chiseko , Villar-Quiles Rocío Nur , Caballero-Ávila Marta , Topf Ana , Nishino Ichizo , Kimonis Virginia , Udd Bjarne , Schoser Benedikt , Zanoteli Edmar , Souza Paulo Victor Sgobbi , Tasca Giorgio , Lloyd Thomas , Lopez-de Munain Adolfo , Paradas Carmen , Pegoraro Elena , Nadaj-Pakleza Aleksandra , De Bleecker Jan , Badrising Umesh , Alonso-Jiménez Alicia , Kostera-Pruszczyk Anna , Miralles Francesc , Shin Jin-Hong , Bevilacqua Jorge Alfredo , Olivé Montse , Vorgerd Matthias , Kley Rudi , Brady Stefen , Williams Timothy , Domínguez-González Cristina , Papadimas George K , Warman-Chardon Jodi , Claeys Kristl G , de Visser Marianne , Muelas Nuria , LaForet Pascal , Malfatti Edoardo , Alfano Lindsay N , Nair Sruthi S , Manousakis Georgios , Kushlaf Hani A , Harms Matthew B , Nance Christopher , Ramos-Fransi Alba , Rodolico Carmelo , Hewamadduma Channa , Cetin Hakan , García-García Jorge , Pál Endre , Farrugia Maria Elena , Lamont Phillipa J , Quinn Colin , Nedkova-Hristova Velina , Peric Stojan , Luo Sushan , Oldfors Anders , Taylor Kate , Ralston Stuart , Stojkovic Tanya , Weihl Conrad , Diaz-Manera Jordi
Published: July 2022

Background

Valosin-containing protein (VCP) disease, caused by mutations in the VCP gene, results in myopathy, Paget’s disease of bone (PBD) and frontotemporal dementia (FTD). Natural history and genotype–phenotype correlation data are limited. This study characterises patients with mutations in VCP gene and investigates genotype–phenotype correlations.

Methods

Descriptive retrospective international study collecting clinical and genetic data of patients with mutations in the VCP gene.

Results

Two hundred and fifty-five patients (70.0% males) were included in the study. Mean age was 56.8±9.6 years and mean age of onset 45.6±9.3 years. Mean diagnostic delay was 7.7±6 years. Symmetric lower limb weakness was reported in 50% at onset progressing to generalised muscle weakness. Other common symptoms were ventilatory insufficiency 40.3%, PDB 28.2%, dysautonomia 21.4% and FTD 14.3%. Fifty-seven genetic variants were identified, 18 of these no previously reported. c.464G>A (p.Arg155His) was the most frequent variant, identified in the 28%. Full time wheelchair users accounted for 19.1% with a median time from disease onset to been wheelchair user of 8.5 years. Variant c.463C>T (p.Arg155Cys) showed an earlier onset (37.8±7.6 year) and a higher frequency of axial and upper limb weakness, scapular winging and cognitive impairment. Forced vital capacity (FVC) below 50% was as risk factor for being full-time wheelchair user, while FVC <70% and being a full-time wheelchair user were associated with death.

Conclusion

This study expands the knowledge on the phenotypic presentation, natural history, genotype–phenotype correlations and risk factors for disease progression of VCP disease and is useful to improve the care provided to patient with this complex disease.
Systematic evaluation of genetic mutations in ALS: a population-based study
Authors: Grassano Maurizio , Calvo Andrea , Moglia Cristina , Sbaiz Luca , Brunetti Maura , Barberis Marco , Casale Federico , Manera Umberto , Vasta Rosario , Canosa Antonio , D’Alfonso Sandra , Corrado Lucia , Mazzini Letizia , Dalgard Clifton , Karra Ramita , Chia Ruth , Traynor Bryan , Chiò Adriano
Published: July 2022

Background

A genetic diagnosis in Amyotrophic Lateral Sclerosis (ALS) can inform genetic counselling, prognosis and, in the light of incoming gene-targeted therapy, management. However, conventional genetic testing strategies are often costly and time-consuming.

Objective

To evaluate the diagnostic yield and advantages of whole-genome sequencing (WGS) as a standard diagnostic genetic test for ALS.

Methods

In this population-based cohort study, 1043 ALS patients from the Piemonte and Valle d’Aosta Register for ALS and 755 healthy individuals were screened by WGS for variants in 42 ALS-related genes and for repeated-expansions in C9orf72 and ATXN2.

Results

A total of 279 ALS cases (26.9%) received a genetic diagnosis, namely 75.2% of patients with a family history of ALS and 21.5% of sporadic cases. The mutation rate among early-onset ALS patients was 43.9%, compared with 19.7% of late-onset patients. An additional 14.6% of the cohort carried a genetic factor that worsen prognosis.

Conclusions

Our results suggest that, because of its high diagnostic yield and increasingly competitive costs, along with the possibility of retrospectively reassessing newly described genes, WGS should be considered as standard genetic testing for all ALS patients. Additionally, our results provide a detailed picture of the genetic basis of ALS in the general population.