bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of Bacterial Pathogens at Genus and Species Levels through Combination of Raman Spectrometry and Deep-Learning Algorithms
Authors: Wang Liang , Tang Jia-Wei , Li Fen , Usman Muhammad , Wu Chang-Yu , Liu Qing-Hua , Kang Hai-Quan , Liu Wei , Gu Bing
Published: October 2022

In this study, we investigated 30 bacterial species belonging to 9 different bacterial genera that were isolated from clinical samples via surfaced enhanced Raman spectroscopy (SERS). A total of 17,149 SERS spectra were harvested from a Raman spectrometer and were further analyzed via machine learning approaches, the results of which showed that the convolutional neural network (CNN) deep learning algorithm could achieve the highest prediction accuracy for recognizing pathogenic bacteria at both the genus and species levels.
NSC19723, a Thiacetazone-Like Benzaldehyde Thiosemicarbazone Improves the Efficacy of TB Drugs
In Vitro
and
In Vivo
Authors: Singh Padam , Rawat Srishti , Agrahari Ashish Kumar , Singh Manisha , Chugh Saurabh , Gurcha Sudagar , Singh Albel , Abrahams Katherine , Besra Gurdyal S. , Asthana Shailendra , Rawat Diwan S. , Singh Ramandeep
Published: October 2022

Mycobacterium tuberculosis
, the causative agent of TB is among the leading causes of death among infectious diseases in humans. This situation has worsened due to the failure of BCG vaccines and the increased number of cases with HIV-TB coinfections and drug-resistant strains.
Omadacycline Is Highly Active
In Vitro
against Mycoplasma genitalium
Authors: Waites Ken B. , Crabb Donna M. , Atkinson T. Prescott , Geisler William M. , Xiao Li
Published: October 2022

There are very few clinical isolates of
Mycoplasma genitalium
available for
in vitro
susceptibility testing. We studied 10 isolates and determined that the new semisynthetic aminomethylcycline omadacycline is active against isolates that are resistant to tetracyclines, macrolides, and quinolones. These data suggest that clinical studies should be performed in order to see if omadacycline may be useful to treat urogenital infections caused by
M. genitalium
.
Overdiagnosis and overuse of diagnostic and screening tests in low-income and middle-income countries: a scoping review
Authors: Albarqouni Loai , Arab-Zozani Morteza , Abukmail Eman , Greenwood Hannah , Pathirana Thanya , Clark Justin , Kopitowski Karin , Johansson Minna , Born Karen , Lang Eddy , Moynihan Ray
Published: October 2022

Objective

Overdiagnosis and overuse of healthcare services harm individuals, take resources that could be used to address underuse, and threaten the sustainability of health systems. These problems are attracting increasing attention in low-income and middle-income countries (LMICs). Unaware of any review of relevant evidence, we conducted a scoping review of the evidence around overdiagnosis and overuse of diagnostic and screening tests in LMICs.

Design

Scoping review.

Methods

We searched PubMed, Embase, PsycINFO, Global Index Medicus for relevant studies published until 24 May 2021, with no restrictions on date or language. We categorised included studies by major focus (overdiagnosis, overuse of tests, or both) and main themes (presence or estimates of extent; drivers; consequences and solutions).

Results

We identified 2763 unique records and included 162 articles reporting on 154 studies across 55 countries, involving over 2.8 million participants and/or requests for tests. Almost half the studies focused on overdiagnosis (70; 45.5%), one-third on overuse of tests (61; 39.6%) and one-fifth on both (23; 14.9%). Common overdiagnosed conditions included malaria (61; 39.6%) and thyroid cancer (25; 16.2%), estimated to be >70% in China. Overused tests included imaging (n=25 studies) such as CT and MRI; laboratory investigations (n=18) such as serological tests and tumour markers; and procedures (n=14) such as colonoscopy. Drivers included fear of conflict with patients and expanding disease definitions. Common consequences included unnecessary treatments such as antimalarials, and wasted resources, with costs of malaria overdiagnosis estimated at US$86 million in Sudan in 1 year alone. Only 9% of studies discussed solutions, which included addressing inappropriately lowered diagnostic thresholds and reforming test-ordering processes.

Conclusions

Overdiagnosis and overuse of tests are widespread in LMICs and generate significant harm and waste. Better understanding of the problems and robust evaluation of solutions is needed, informed by a new global alliance of researchers and policy-makers.
Applying learning health systems thinking in codeveloping integrated tuberculosis interventions in the contexts of COVID-19
Authors: van Rensburg André Janse , Petersen Inge , Awotiwon Ajibola , Bachmann Max Oscar , Curran Robyn , Murdoch Jamie , Ras Christy Joy , Fairall Lara
Published: October 2022

The COVID-19 pandemic reversed much of global progress made in combatting tuberculosis, with South Africa experiencing one of the largest impacts on tuberculosis detection. The aim of this paper is to share our experiences in applying learning health systems (LHS) thinking to the codevelopment of an intervention improving an integrated response to COVID-19 and tuberculosis in a South African district. A sequential partially mixed-methods study was undertaken between 2018 and 2021 in the district of Amajuba in KwaZulu-Natal. Here, we report on the formulation of a Theory of Change, codesigning and refining proposed interventions, and piloting and evaluating codesigned interventions in primary healthcare facilities, through an LHS lens. Following the establishment and formalisation of a district Learning Community, diagnostic work and a codevelopment of a theory of change, intervention packages tailored according to pandemic lockdowns were developed, piloted and scaled up. This process illustrates how a community of learning can generate more responsive, localised interventions, and suggests that the establishment of a shared space of research governance can provide a degree of resilience to facilitate adaption to external shocks. Four main lessons have been gleaned from our experience in adopting an LHS approach in a South African district, which are (1) the importance of building and sustaining relationships, (2) the utility of colearning, coproduction and adaptive capacity, (3) the centrality of theory-driven systems strengthening and (4) reflections on LHS as a framework.
Retrospective analysis on the effect of Reverse Diabetes2 Now on kidney function in patients with type 2 diabetes with impaired kidney function
Authors: Wilmsen Nathalie , Pijl Hanno , Geerlings Willem , Navis Gerjan
Published: October 2022

Objective

Type 2 diabetes is one of the main causes of kidney damage. Recent intervention studies suggest that the progression of type 2 diabetes can be halted, or even brought into remission by lifestyle interventions. In a pragmatic trial, the Reverse Diabetes2 Now programme (RD2N, NL: Keer Diabetes2 Om), a multicomponent lifestyle intervention, reduced the need for bloodglucose lowering medications up to 24 months.

Research design and methods

Here, we retrospectively investigate the effect of RD2N on markers of kidney function in patients selected for impaired kidney function at baseline (eGFR <70 mL/min/1.73 m2(n=45). Baseline data were retrieved from the intervention database and follow-up data on renal markers were collected from routine medical records. Wilcoxon non-parametric tests were used to assess changes over 6 and 12 months.

Results

After 6 months median eGFR increased significantly from 62.0 (IQR 55.5–65.0) to 69.0 (IQR 55.0–76.5) mL/min/1.73 m2(p=0.002). Median albumin/creatinine ratio (n=26) remained within the normal range (<3 mg/mmol). The effect on eGFR was similar after exclusion of patients in whom medication was changed (median eGFR 62.0 ((IQR 59.5–66.0) to 69.0 (IQR 60.0–77.0) mL/min/1.73 m2, p=0.006, n=29), suggesting that the effect on eGFR is not related to medication changes. At 12 months, eGFR was not significantly changed (n=22, median eGFR 63.5 mL/min/1.73 m2(IQR 58.5–71.0), p=0.067).

Conclusions

The retrospective nature of this study and the despite guidelines limited availability of renal markers in routine type 2 diabetes care are limiting. Nevertheless, these data support a favourable effect of RD2N on renal function. Further research, with proper documentation of renal function, urinary protein excretion and dietary intake, is needed to substantiate these results, ideally in a large-scale prospective cohort study.
Retrospective observational study of the influence of the COVID-19 outbreak on infants’ hospitalisation for acute bronchiolitis
Authors: Berdah Laura , Romain Anne-Sophie , Rivière Simon , Schnuriger Aurélie , Perrier Marine , Carbajal Ricardo , Lorrot Mathie , Guedj Romain , Corvol Harriet
Published: October 2022

Objectives

Acute bronchiolitis is a major public health issue with high number of infants hospitalised worldwide each year. In France, hospitalisations mostly occur between October and March and peak in December. A reduction of emergency visits for bronchiolitis has been observed at onset of the COVID-19 outbreak. We aimed to assess the pandemic effects on the hospitalisations for bronchiolitis during the 2020–2021 winter (COVID-19 period) compared with three previous winters (pre-COVID-19).

Design

Retrospective, observational and cross-sectional study.

Setting

Tertiary university paediatric hospital in Paris (France).

Participants

All infants aged under 12 months who were hospitalised for acute bronchiolitis during the autumn/winter seasons (1 October to 31 March) from 2017 to 2021 were included. Clinical and laboratory data were collected using standardised forms.

Results

During the COVID-19 period was observed, a 54.3% reduction in hospitalisations for bronchiolitis associated with a delayed peak (February instead of November–December). Clinical characteristics and hospitalisation courses were substantially similar. The differences during the COVID-19 period were: smaller proportion of infants with comorbidities (8% vs 14% p=0.02), lower need for oxygen (45% vs 55%, p=0.01), higher proportions of metapneumovirus, parainfluenzae 3, bocavirus, coronavirus NL63 and OC43 (all p≤0.01) and no influenza. The three infants positive for SARS-CoV-2 were also positive for respiratory syncytial virus, suggesting that SARS-CoV-2 alone does not cause bronchiolitis, despite previous assumptions.

Conclusion

The dramatic reduction in infants’ hospitalisations for acute bronchiolitis is an opportunity to change our future habits such as advising the population to wear masks and apply additional hygiene measures in case of respiratory tract infections. This may change the worldwide bronchiolitis burden and improve children respiratory outcomes.
Pathways between neighbourhood factors, stress and glycaemic control in individuals with type 2 diabetes in Southeastern United States: a cross-sectional pathway analysis
Authors: Mosley-Johnson Elise , Walker Rebekah , Hawks Laura , Walker Shannon L , Mendez Carlos , Campbell Jennifer A , Egede Leonard E
Published: October 2022

Objectives

Understanding the pathway by which neighbourhood factors influence glycaemic control may be crucial to addressing health disparities in diabetes. This study aimed to examine if the pathway between neighbourhood factors and glycaemic control is mediated by stress.

Design

Structured equation modelling (SEM) was used to investigate direct and indirect effects in the relationship between neighbourhood factors, stress and glycaemic control, with standardised estimates to allow comparison of paths.

Participants

Data was obtained from 615 adults with type 2 diabetes in the Southeastern United States.

Primary and secondary outcome measures

The primary outcome variable was glycaemic control determined by glycated haemoglobin (HbA1c) within the prior 6 months. Neighbourhood factors included neighbourhood violence, aesthetic quality of the neighbourhood, access to healthy food, and social cohesion. Stress was measured using the perceived stress scale.

Results

In the final model (χ2(158)=406.97, p<0.001, root mean square error of approximation=0.05, p-close 0.38, Comparative Fit Index=0.97, Tucker-Lewis index=0.96, the coefficient of determination=1.0), violence (r=0.79, p=0.006), neighbourhood aesthetics (r=0.74, p=0.02) and social cohesion (r=0.57, p=0.04) were significantly associated with higher perceived stress. Stress (r=0.06, p=0.004) was directly associated with higher glycaemic control. Significant indirect effects existed between violence and higher HbA1c (r=0.05, p=0.04). After controlling for other neighbourhood factors, there was no significant relationship between access to healthy food and either stress or glycaemic control.

Conclusions

While a number of neighbourhood factors were directly associated with stress, only neighbourhood violence had a significant indirect effect on glycaemic control via stress within the tested pathway. Future studies should examine individual-level stress management interventions and should consider community-level interventions targeting neighbourhood violence as strategies for addressing disparities in diabetes.
Retrospective cohort study to assess the association between treatment with tocilizumab and mortality among mechanically ventilated patients with COVID-19
Authors: Skarbinski Jacek , Liu Liyan , Hong Vennis , Amsden Laura B , Fireman Bruce H , Yau Vincent M , Incerti Devin , Qian Lei , Fischer Heidi , Ackerson Bradley K , Shaw Sally F , Tartof Sara Y
Published: October 2022

Objectives

Assess the association between tocilizumab administration and clinical outcomes among mechanically ventilated patients with COVID-19 pneumonia.

Design

Retrospective cohort study.

Setting

Large integrated health system with 9 million members in California, USA.

Participants

4185 Kaiser Permanente members hospitalised with COVID-19 pneumonia requiring invasive mechanical ventilation (IMV).

Interventions

Receipt of tocilizumab within 10 days of initiation of IMV.

Outcome measures

Using a retrospective cohort of consecutive patients hospitalised with COVID-19 pneumonia who required IMV in a large integrated health system in California, USA, we assessed the association between tocilizumab administration and 28-day mortality, time to extubation from IMV and time to hospital discharge.

Results

Among 4185 patients, 184 received tocilizumab and 4001 patients did not receive tocilizumab within 10 days of initiation of IMV. After inverse probability weighting, baseline characteristics were well balanced between groups. Patients treated with tocilizumab had a similar risk of death in the 28 days after intubation compared with patients not treated with tocilizumab (adjusted HR (aHR), 1.21, 95% CI 0.98 to 1.50), but did have a significantly longer time-to-extubation (aHR 0.71; 95% CI 0.57 to 0.88) and time-to-hospital-discharge (aHR 0.66; 95% CI 0.50 to 0.88). However, patients treated with tocilizumab ≤2 days after initiation of IMV had a similar risk of mortality (aHR 1.47; 95% CI 0.96 to 2.26), but significantly shorter time-to-extubation (aHR 0.37; 95% CI 0.23 to 0.58) and time-to-hospital-discharge (aHR 0.31; 95% CI CI 0.17 to 0.56) compared with patients treated with tocilizumab 3–10 days after initiation of IMV.

Conclusions

Among mechanically ventilated patients with COVID-19, the risk of death in the 28-day follow-up period was similar, but time-to-extubation and time-to-hospital-discharge were longer in patients who received tocilizumab within 10 days of initiation of IMV compared with patients who did not receive tocilizumab.
Phase III, randomised, double-blind, placebo-controlled, multicentre trial to evaluate the efficacy and safety of rhGAD65 to preserve endogenous beta cell function in adolescents and adults with recently diagnosed type 1 diabetes, carrying the genetic HLA DR3-DQ2 haplotype: the DIAGNODE-3 study protocol
Authors: Ludvigsson Johnny , Eriksson Linnea , Nowak Christoph , Teixeira Pedro F , Widman Martina , Lindqvist Anton , Casas Rosaura , Lind Marcus , Hannelius Ulf
Published: October 2022

Introduction

Type 1 diabetes (T1D) is an autoimmune disease leading to the destruction of the insulin-producing beta cells resulting in insulin deficiency and hyperglycaemic. Today, no approved therapy exists to halt this detrimental immunologic process. In a recent phase 2b study, intralymphatic administration of recombinant human glutamic acid decarboxylase 65 kDa (rhGAD65) adsorbed to Alhydrogel adjuvant to individuals recently diagnosed with T1D and carrying the HLA DR3-DQ2 haplotype showed promising results in preserving endogenous insulin secretion, confirming the results of a large meta-analysis of three randomised placebo-controlled trials of subcutaneous rhGAD65. The aim of the current precision medicine phase 3 study is to determine whether intralymphatic administration of rhGAD65 preserves insulin secretion and improves glycaemic control in presumed responder individuals with recently diagnosed T1D carrying HLA DR3-DQ2.

Methods and analysis

Individuals ≥12 and <29 years recently diagnosed with T1D (<6 months) will be screened for the HLA DR3-DQ2 haplotype, endogenous insulin production estimated by fasting C-peptide and presence of GAD65 antibodies. 330 patients are planned to be randomised to 3 monthly intralymphatic injections of rhGAD65 or placebo (both accompanied by oral vitamin D supplementation), followed by 22 months of follow-up. The study is powered to detect a treatment effect in the two coprimary endpoints; change from baseline in AUC(0-120min)C-peptide levels during a mixed meal tolerance test, and change from baseline in glycaemic control estimated by haemoglobin A1c at 24 months. Secondary endpoints include effects on glucose patterns collected by masked continuous glucose monitoring, proportion of patients in partial remission and number of episodes of severe hypoglycaemia and/or diabetic ketoacidosis.

Ethics and dissemination

The trial is approved by Ethics Committees in Poland (124/2021), the Netherlands (R21.089), Sweden (2021-05063), Czech Republic (EK-1144/21), Germany (2021361) and Spain (21/2021). Results will be published in international peer-reviewed scientific journals and presented at national and international conferences.

Trial registration number

EudraCT identifier: 2021-002731-32, NCT identifier:NCT05018585.
Built Environments And Child Health in WalEs and AuStralia (BEACHES): a study protocol
Authors: Pedrick-Case Rebecca , Bailey Rowena , Beck Ben , Beesley Bridget , Boruff Bryan , Brophy Sinead , Cross Donna , Dhamrait Gursimran , Duncan John , Gething Peter , Johnson Rhodri D , Lyons Ronan A , Mizen Amy , Murray Kevin , Pouliou Theodora , Rafferty James , Robinson Trina , Rosenberg Michael , Schipperijn Jasper , Thompson Daniel A , Trost Stewart G , Watkins Alan , Stratton Gareth , Fry Richard , Christian Hayley , Griffiths Lucy J
Published: October 2022

Introduction

Childhood obesity and physical inactivity are two of the most significant modifiable risk factors for the prevention of non-communicable diseases (NCDs). Yet, a third of children in Wales and Australia are overweight or obese, and only 20% of UK and Australian children are sufficiently active. The purpose of the Built Environments And Child Health in WalEs and AuStralia (BEACHES) study is to identify and understand how complex and interacting factors in the built environment influence modifiable risk factors for NCDs across childhood.

Methods and analysis

This is an observational study using data from five established cohorts from Wales and Australia: (1) Wales Electronic Cohort for Children; (2) Millennium Cohort Study; (3) PLAY Spaces and Environments for Children’s Physical Activity study; (4) The ORIGINS Project; and (5) Growing Up in Australia: the Longitudinal Study of Australian Children. The study will incorporate a comprehensive suite of longitudinal quantitative data (surveys, anthropometry, accelerometry, and Geographic Information Systems data) to understand how the built environment influences children’s modifiable risk factors for NCDs (body mass index, physical activity, sedentary behaviour and diet).

Ethics and dissemination

This study has received the following approvals: University of Western Australia Human Research Ethics Committee (2020/ET000353), Ramsay Human Research Ethics Committee (under review) and Swansea University Information Governance Review Panel (Project ID: 1001). Findings will be reported to the following: (1) funding bodies, research institutes and hospitals supporting the BEACHES project; (2) parents and children; (3) school management teams; (4) existing and new industry partner networks; (5) federal, state and local governments to inform policy; as well as (6) presented at local, national and international conferences; and (7) disseminated by peer-reviewed publications.
Influence of social networks in healthcare on preparation for selection procedures of health professions education: a Dutch interview study
Authors: Mulder Lianne , Wouters Anouk , Fikrat-Wevers Suzanne , Koster Andries S , Ravesloot Jan Hindrik , Croiset Gerda , Kusurkar Rashmi A
Published: October 2022

Objectives

Health professions education (HPE) students are often not representative of the populations they will serve. The underrepresentation of non-traditional students is problematic because diversity is essential for promoting excellence in health education and care. This study aimed to understand the perceptions of traditional and non-traditional students regarding facilitators and barriers in preparing for HPE selection procedures, and to determine the role of social networks in their decision-making and preparations to apply.

Methods

A qualitative study was conducted with 26 Dutch youth who were interested in university-level HPE programmes. Semistructured interviews and sociograms were analysed using thematic analysis, adopting a constructivist approach.

Results

Twenty-six high school students participated, with traditional and non-traditional backgrounds, with and without social networks in healthcare and higher education. Two themes were constructed. First, four high-impact facilitators helped to overcome barriers to apply and in preparation for selection: access to a social network connection working or studying in healthcare, to correct information, to healthcare experience and to a social network connection in higher education. Lack of information was the main barrier while access to social network connections in healthcare was the main facilitator to overcome this barrier. However, this access was unevenly distributed. Second, access alone is not enough: the need for agency to make use of available facilitators is also essential.

Conclusions

The themes are discussed using intersectionality. Traditional students with access to facilitators develop their self-efficacy and agency within social structures that privilege them, whereas non-traditional students must develop those skills without such structures. Our findings provide recommendations for the ways in which universities can remove barriers that cause unequal opportunities to prepare for the selection of HPE programmes. Along with equitable admissions, these recommendations can help to achieve a more representative student population and subsequently a better quality of health education and care.
Canadian infants presenting with Brief Resolved Unexplained Events (BRUEs) and validation of clinical prediction rules for risk stratification: a protocol for a multicentre, retrospective cohort study
Authors: Nama Nassr , Hosseini Parnian , Lee Zerlyn , Picco Kara , Bone Jeffrey N , Foulds Jessica L , Gagnon Josée Anne , Sehgal Anupam , Quet Julie , Drouin Olivier , Luu Thuy Mai , Vomiero Gemma , Kanani Ronik , Holland Joanna , Goldman Ran D , Kang Kristopher T , Mahant Sanjay , Jin Falla , Tieder Joel S , Gill Peter J
Published: October 2022

Introduction

Brief Resolved Unexplained Events (BRUEs) are a common presentation among infants. While most of these events are benign and self-limited, guidelines published by the American Academy of Pediatrics inaccurately identify many patients as higher-risk of a serious underlying aetiology (positive predictive value 5%). Recently, new clinical prediction rules have been derived to more accurately stratify patients. This data were however geographically limited to the USA, with no large studies to date assessing the BRUE population in a different healthcare setting. The study’s aim is to describe the clinical management and outcomes of infants presenting to Canadian hospitals with BRUEs and to externally validate the BRUE clinical prediction rules in identified cases.

Methods and analysis

This is a multicentre retrospective study, conducted within the Canadian Paediatric Inpatient Research Network (PIRN). Infants (<1 year) presenting with a BRUE at one of 11 Canadian paediatric centres between 1 January 2017 and 31 December 2021 will be included. Eligible patients will be identified using diagnostic codes.

The primary outcome will be the presence of a serious underlying illness. Secondary outcomes will include BRUE recurrence and length of hospital stay. We will describe the rates of hospital admissions and whether hospitalisation was associated with an earlier diagnosis or treatment. Variation across Canadian hospitals will be assessed using intraclass correlation coefficient. To validate the newly developed clinical prediction rule, measures of goodness of fit will be evaluated. For this validation, a sample size of 1182 is required to provide a power of 80% to detect patients with a serious underlying illness with a significance level of 5%.

Ethics and dissemination

Ethics approval has been granted by the UBC Children’s and Women’s Research Board (H21-02357). The results of this study will be disseminated as peer-reviewed manuscripts and presentations at national and international conferences.
Autologous cultured adipose derived mesenchymal stem cells combined with hyaluronic acid hydrogel in the treatment of discogenic low back pain: a study protocol for a phase II randomised controlled trial
Authors: Zhang Jing , Sun Tianze , Zhang Wentao , Yang Ming , Li Zhonghai
Published: October 2022

Introduction

Discogenic low back pain (DLBP) is a common disease, and its occurrence is closely related to intervertebral disc (IVD) degeneration. At present, none of the traditional treatment methods can repair the degenerated IVD. The emergence of stem cell therapy makes it possible to repair and regenerate IVD tissue, among which adipose derived mesenchymal stem cells (ADMSCs) transplantation therapy has become a hot spot of current research. Therefore, this trial aimed to investigate the safety and efficacy of using autologous cultured ADMSCs combined with hyaluronic acid (HA) hydrogel in the treatment of DLBP.

Methods and analysis

This study is a randomised, dose-escalation, placebo-controlled, double-blind, single-centre, phase II clinical trial to evaluate the efficacy and safety of autologous cultured ADMSCs combined with HA hydrogel in the treatment of patients with DLBP. The 100 eligible patients will be randomly divided into three experimental groups with different doses and one placebo control group in a ratio of 1:1:1:1. All patients will undergo liposuction to obtain ADMSCs, followed by autologous cultured ADMSC mixtures or placebo transplantation after 3 weeks. The patients will be followed up to 24 months after the transplant. The primary end point of this trial is the Visual Analogue Scale. Secondary end points include the Oswestry Disability Index, Japanese Orthopaedic Association Scores, the Mos 36-item short form, the Modic classification, Pfirrmann grade, height and segment range of motion of the IVD, vital signs (temperature, pulse, respiration, blood pressure), blood routine, liver and kidney function, immunological examination, urinalysis and treatment emergent adverse events.

Ethics and dissemination

The study protocol has been approved by the Ethics Committee of the First Affiliated Hospital of Dalian Medical University and registered in the Chinese Clinical Trial Registry. Dissemination of the results will be presented at a conference and in peer-reviewed publications.

Trial registration number

ChiCTR2200058291.
Minimally invasivE versus open total GAstrectomy (MEGA): study protocol for a multicentre randomised controlled trial (DRKS00025765)
Authors: Nickel Felix , Studier-Fischer Alexander , Hausmann David , Klotz Rosa , Vogel-Adigozalov Sophia Lara , Tenckhoff Solveig , Klose Christina , Feisst Manuel , Zimmermann Samuel , Babic Benjamin , Berlt Felix , Bruns Christiane , Gockel Ines , Graf Sandra , Grimminger Peter , Gutschow Christian A , Hoeppner Jens , Ludwig Kaja , Mirow Lutz , Mönig Stefan , Reim Daniel , Seyfried Florian , Stange Daniel , Billeter Adrian , Nienhüser Henrik , Probst Pascal , Schmidt Thomas , Müller-Stich Beat Peter
Published: October 2022

Introduction

The only curative treatment for most gastric cancer is radical gastrectomy with D2 lymphadenectomy (LAD). Minimally invasive total gastrectomy (MIG) aims to reduce postoperative morbidity, but its use has not yet been widely established in Western countries. Minimally invasivE versus open total GAstrectomy is the first Western multicentre randomised controlled trial (RCT) to compare postoperative morbidity following MIG vs open total gastrectomy (OG).

Methods and analysis

This superiority multicentre RCT compares MIG (intervention) to OG (control) for oncological total gastrectomy with D2 or D2+LAD. Recruitment is expected to last for 2 years. Inclusion criteria comprise age between 18 and 84 years and planned total gastrectomy after initial diagnosis of gastric carcinoma. Exclusion criteria include Eastern Co-operative Oncology Group (ECOG) performance status >2, tumours requiring extended gastrectomy or less than total gastrectomy, previous abdominal surgery or extensive adhesions seriously complicating MIG, other active oncological disease, advanced stages (T4 or M1), emergency setting and pregnancy.

The sample size was calculated at 80 participants per group. The primary endpoint is 30-day postoperative morbidity as measured by the Comprehensive Complications Index. Secondary endpoints include postoperative morbidity and mortality, adherence to a fast-track protocol and patient-reported quality of life (QoL) scores (QoR-15, EUROQOL EuroQol-5 Dimensions-5 Levels (EQ-5D), EORTC QLQ-C30, EORTC QLQ-STO22, activities of daily living and Body Image Scale). Oncological endpoints include rate of R0 resection, lymph node yield, disease-free survival and overall survival at 60-month follow-up.

Ethics and dissemination

Ethical approval has been received by the independent Ethics Committee of the Medical Faculty, University of Heidelberg (S-816/2021) and will be received from each responsible ethics committee for each individual participating centre prior to recruitment. Results will be published open access.

Trial registration number

DRKS00025765.
Novel drug-repository contact lens for prolonging the antimicrobial-cornea interaction for bacterial keratitis treatment: randomised controlled trial results
Authors: Daniel Raj Ponniah Lional Raj , Ranilakshmi Velupillai , Anandan Heber , Caroline Jeyakumar , Arulanandham Antonysamy
Published: October 2022

Background/Aims

Microbial keratitis can cause unilateral blindness, but the drug delivery treatment options are poor. Therefore, this study evaluated the efficacy of a novel therapeutic drug-depository contact lens (DDCL) for bacterial keratitis (BK) treatment. The lens was designed to increase the corneal lesion-antimicrobial drug interaction time.

Methods

Patients with BK were randomised (1:1) into two groups: topical antimicrobial treatment only (group 1) and DDCL plus antimicrobial treatment (group 2). Both groups received 0.5% moxifloxacin. We evaluated BK recovery, anterior chamber (AC) reactions, corneal haze and pain (on a 10-point scale) 12 hours and 1, 3, 5 and 14 days after treatment.

Results

The baseline corneal-infiltration (ie, BK severity) values were comparable for groups 1 (18 cases) and 2 (17 cases) (p=0.92). After 12 hours, the scores improved in both groups and continued to improve throughout the follow-up period; the improvements were more pronounced in group 2 than in group 1 (all p<0.05). Complete recovery occurred on days 14 and 5 in groups 1 and 2, respectively. Furthermore, the AC reaction resolved by day 3 in group 2. The baseline pain scores were also comparable between groups 1 and 2 (p=0.52) and decreased throughout the follow-up period (all p<0.05); the decrease was more pronounced in group 2.

Conclusions

Novel DDCLs augment the drug-lesion interaction time by prolonging corneal antimicrobial availability, which hastens corneal healing in BK. Thus, a DDCL may decrease the antibiotic regimen and improve patient tolerance, eliminating the necessity for a loading dose.

Trial registration number

CTRI/2020/08/027088.
Sociodemographic and psychological characteristics influencing patients’ willingness to participate in clinical trials
Authors: Gouveia Rita , Cruz Vitor Tedim , Almeida Luís
Published: October 2022

Background/Aims

Clinical trials are fundamental for the development of new medicines and patient participation is based on free consent. Our study sought to identify psychological characteristics that may influence patient willingness to participate in a clinical trial.

Methods

A total of 100 participants were invited to participate with 80% positive response rate. The psychological characteristics of each patient were evaluated using the following validated psychometric scales: Self-Efficacy Scale, Curiosity, Exploration Inventory-Trait, Social Support Satisfaction, State-Trait Anxiety Inventory and Social Avoidance and Distress, and Fear of Negative Evaluation.

Results

Patients who agreed to participate in the clinical trial were significantly younger than those who refused (p=0.028). There were no differences in sex, lifestyle, employment status, monthly income or education. After adjusting for age and sex, patients who agreed to participate scored significantly higher in the following: self-efficacy total score (p<0.001), effectiveness in adversity (p<0.001), social effectiveness (p<0.001) and initiation and persistence (p<0.001); social support total score (p<0.001), family satisfaction (p=0.015), friendship satisfaction (p<0.001), social activities satisfaction (p=0.002) and intimacy (p<0.001); total curiosity score (p<0.001), absorption (p<0.001) and exploration (p<0.001). Compared with patients who agreed to participate, those who refused scored significantly higher for both state (p<0.001) and trait anxiety (p<0.001), fear of negative evaluation (p<0.001) and social avoidance and distress (p<0.001).

Conclusions

Patients who were willing to participate in clinical trials exhibited different psychological characteristics to patients who refused. Specifically, they were more curious and self-efficacious, less anxious and reported a higher level of social support than patients who declined to participate. Identifying characteristics that condition the individual’s decision to participate in a clinical trial has important implications for the development of patient-focused communication strategies and improved recruitment approaches.
Surgical implementation gap: an interrupted time series analysis with interviews examining the impact of surgical trials on surgical practice in England
Authors: Schmidtke Kelly Ann , Evison Felicity , Grove Amy , Kudrna Laura , Tucker Olga , Metcalfe Andy , Bradbury Andrew W , Bhangu Aneel , Lilford Richard
Published: October 2022

Objectives

Landmark studies published near the turn of the 21st century found an implementation gap concerning the effect of evidenced-based findings on clinical practice. The current study examines the uptake of six trials that produced actionable findings to describe the effects of evidence on practice and the reasons for those effects.

Design

A sequential, explanatory mixed methods study was conducted. First, a quantitative study assessed whether actionable findings from large, publicly funded elective surgical trials influenced practice. Subsequently, qualitative interviews were conducted to explain the quantitative findings.

Setting

Changes in NHS-funded practice were tracked across hospitals in England. Interviews were conducted online.

Data and participants

The six surgical trials were funded and published by England’s National Institute for Health Research’s Health Technology Assessment programme between 2006 and 2015. Quantitative time series analyses used data about the frequencies or proportions of relevant surgical procedures conducted in England between 2001 and 2020. Subsequently, qualitative interviews were conducted with 25 participants including study authors, surgeons and other healthcare staff in the supply chain. Transcripts were coded to identify major temporal events and Consolidated Framework for Implementation Research (CFIR) domains/constructs that could influence implementation. Findings were synthesised by clinical area.

Results

The quantitative analyses reveal that practice changed in accordance with findings for three trials. In one trial (percutaneous vs nasogastric tube feed after stroke), the change took a decade to occur. In another (patella resurfacing), change anticipated the trial findings. In the third (abdominal aortic aneurysm repair), changes tracked the evolving evidence base. In the remaining trials (two about varicose veins and one about gastric reflux), practice did not change in line with findings. For varicose veins, the results were superseded by a further trial. For gastric reflux, surgical referrals declined as medical treatment increased. The exploratory qualitative analysis informed by CFIR found that evidence from sources apart from the trial in question was mentioned as a reason for non-adoption in the three trials where evidence did not affect practice and in the trial where uptake was delayed. There were no other consistent patterns in the qualitative data.

Conclusion

While practice does not always change in the direction indicated by clinical trials, our results suggest that individuals, official committees and professional societies do assimilate trial evidence. Decision-makers seem to respond to the totality of evidence such that there are often plausible reasons for not adopting the evidence of any one trial in isolation.
Experiences using a progestin-only pill in an over-the-counter environment in the United States: a cross-sectional survey
Authors: Grindlay Kate , Key Katherine , Zuniga Carmela , Wollum Alexandra , Grossman Daniel , Blanchard Kelly
Published: October 2022

Background

Efforts are underway to make a progestin-only pill (POP) over the counter (OTC) in the United States (US); however, little is known about POP user experiences, which could impact uptake and continuation.

Methods

From January 2020–September 2021, we conducted a cross-sectional online survey with individuals who used OTC POPs in a US trial. We calculated descriptive statistics and Pearson chi-square and Fisher’s exact tests to assess menstrual bleeding acceptability, how OTC POP experiences compared with prior contraceptive methods, and preferred ways to get answers to questions during OTC POP use.

Results

Among 550 adult and 115 adolescent participants, 80% (n=531) felt their menstrual bleeding was acceptable. Participants reported a range of menstrual bleeding experiences compared with prior long-acting or hormonal methods used; 58% (n=84) said the POP bleeding was similar or better and 36% (n=53) said it was worse. Among participants who used contraception in the month prior to the trial, 77% (n=201) said their overall OTC POP experience was similar or better. Top benefits compared with prior methods included less worry about pregnancy, ease of access, fewer side effects, and greater decision-making power. Adults preferred to get answers about OTC POPs via webpage or app, whereas teens preferred asking pharmacists or other healthcare providers.

Conclusions

Overall, OTC POP users in a trial setting found the menstrual bleeding acceptable and the method similar to or better than previous methods. POP labelling should provide clear messaging about bleeding changes users may experience.
Differing strategies for sudden death prevention in hypertrophic cardiomyopathy
Authors: Maron Martin S , Rowin Ethan , Spirito Paolo , Maron Barry J
Published: October 2022

Sudden death (SD) has traditionally been the most visible and feared complication of hypertrophic cardiomyopathy (HCM). Substantial progress in reducing the occurrence of these catastrophic events represents a new paradigm in disease management. Prevention of SD in HCM has resulted from introduction of primary prevention ICDs that reliably terminate life-threatening ventricular tachyarrhythmias, as well as a matured risk stratification algorithm capable of reliably identifying those patients at highest risk. This initiative has been a major determinant of reducing HCM-related mortality to a low rate of 0.5%/year. In such a heterogeneous heart disease as HCM, no perfect risk stratification strategy is possible, and available approaches differ in terms of sensitivity and specificity for identifying patients with SD risk. Major cardiovascular societies, American Heart Association/American College of Cardiology in the USA and European Society of Cardiology in Europe have promoted different risk stratification guidelines creating the potential for judging SD risk in a given HCM patient differently based on commitment to a particular societal guideline or country of residence. In this review, we provide a critical but balanced assessment of these two divergent SD prevention strategies with regard to their respective strengths and weaknesses, as a guide to clinicians directly engaged in this important management issue.
Prevention and treatment of premature ischaemic heart disease with European Society of Cardiology Guidelines
Authors: Zeitouni Michel , Sulman David , Silvain Johanne , Kerneis Mathieu , Guedeney Paul , Barthelemy Olivier , Brugier Delphine , Sabouret Pierre , Procopi Niki , Collet Jean-Philippe , Montalescot Gilles
Published: October 2022

Objective

To determine if the changes in the European Society Cardiology/European Atherosclerotic Society (ESC/EAS) guidelines improved the identification for primary prevention therapy in young adults at risk of a premature myocardial infarction.

Methods

Patients admitted for a first ST-segment elevation myocardial infarction (STEMI) in the ePARIS registry (n=2757) between 2010 and 2018 were classified by age: <55, 55–65 and >65 years old. Using Systematic Coronary Risk Estimation 2, we evaluated whether patients would have been detected and treated with primary prevention statins before their first STEMI based on the 2021 EAS/ESC guidelines versus 2019 and 2016 guidelines. Eligibility for intensive proprotein convertase subtilisin/kexin type 9 (PCSK9i) in secondary prevention was also assessed.

Results

Following 2021 ESC guidelines, 62.5% of individuals aged <55 years old would have been eligible for statins before their first STEMI, similarly to older age categories. In comparison, only 17% and 18% of young individuals would have been eligible for primary prevention statins prior to their first STEMI with 2016 and 2019 guidelines, compared with group 55–65 years (41% and 35%) and >65 years old (19% and 72%), p<0.01. After their first STEMI, 25% of patients <55 years would be eligible for PCSK9i, compared with 23.2% and 15% in patients aged 55–65 years and >65 years.

Conclusions

The 2021 ESC guidelines allowed a much better detection of young individuals before their first STEMI than prior ESC guidelines. In secondary prevention, most of young individuals did not reach low-density lipoprotein cholesterol levels recommended, but only one quarter would be eligible for PCSK9i.
Systematic comparison with autoimmune liver disease identifies specific histological features of immune checkpoint inhibitor-related adverse events
Authors: Coukos Alexander , Vionnet Julien , Obeid Michel , Bouchaab Hasna , Peters Solange , Latifyan Sofiya , Wicky Alexandre , Michielin Olivier , Chtioui Haithem , Moradpour Darius , Fasquelle François , Sempoux Christine , Fraga Montserrat
Published: October 2022

Background

Immune checkpoint inhibitors (ICIs) have become a mainstay of cancer treatment. Their immune-boosting quality has one major drawback, their proclivity to induce a broad array of immune-related adverse events (irAEs) affecting, among others, the liver and sharing some similarities with classic autoimmune liver diseases (AILD).We aimed to compare clinical, laboratory and histological features of patients with liver-related irAEs and AILD.

Methods

We systematically compared liver irAEs with AILD, namely autoimmune hepatitis (AIH) and primary biliary cholangitis, regarding their clinical, laboratory, and histological features.

Results

Twenty-seven patients with liver irAEs (ICI group) and 14 patients with AILD were identified. We observed three distinct ICI-induced histological liver injury patterns: hepatitic (52%), cholangitic (19%), and mixed (29%). When comparing the ICI and AILD groups, centrilobular injury as well as granuloma formation were more prevalent in the former (p=0.067 and 0.002, respectively). CD4+/CD8+ T cell ratios were heterogeneous between the two groups, without statistically significant difference but with a trend toward increased CD8+ T cells among hepatitic irAEs as compared with AIH. Pattern of liver function test alteration was predictive for the type of irAEs but did not correlate with histological severity.

Conclusions

Liver irAEs have broad clinical, laboratory and histological presentations. Histological features of irAEs and AILD are distinct, likely underpinning their different immunological mechanisms.