MASLD: a systemic metabolic disorder with cardiovascular and malignant complications

Non-alcoholic fatty liver disease (NAFLD) has rapidly become the most common chronic liver disease globally and is currently estimated to affect up to 38% of the global adult population. NAFLD is a multisystem disease where systemic insulin resistance and related metabolic dysfunction play a pathogenic role in the development of NAFLD and its most relevant liver-related morbidities (cirrhosis, liver failure and hepatocellular carcinoma) and extrahepatic complications, such as cardiovascular disease (CVD), type 2 diabetes mellitus, chronic kidney disease, and certain types of extrahepatic cancers. In 2023, three large multinational liver associations proposed that metabolic dysfunction-associated steatotic liver disease (MASLD) should replace the term NAFLD; the name chosen to replace non-alcoholic steatohepatitis was metabolic dysfunction-associated steatohepatitis (MASH). Emerging epidemiological evidence suggests an excellent concordance rate between NAFLD and MASLD definitions—that is, ~99% of individuals with NAFLD meet MASLD criteria. In this narrative review, we provide an overview of the literature on (a) the recent epidemiological data on MASLD and the risk of developing CVD and malignant complications, (b) the underlying mechanisms by which MASLD (and factors strongly linked with MASLD) may increase the risk of these extrahepatic complications and (c) the diagnosis and assessment of CVD risk and potential treatments to reduce CVD risk in people with MASLD or MASH.

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Empiric use of standard triple therapy in Helicobacter pylori eradication does not require readjustment in the clarithromycin resistance cut-off point

We appreciate the considerations of Hsu et al about the recommendation of empiric first-line therapies in our Maastricht VI/Florence consensus report for the management of Helicobacter pylori.1 2 We fully agree that H. pylori eradication therapy should aim at a cure rate of ≥90%. This also meets the expectation of patients as referred by the authors from a real-world expectation survey of the Asia-Pacific region.3 However, we disagree that the cut-off for clarithromycin resistance, at least for now, is too high at 15% for triple therapy consisting of proton pump inhibitor (PPI), amoxicillin and clarithromycin used as empirical first-line option.2 Hsu et al suggest a cutoff for clarithromycin resistance at or below 5 % for the empirical use of PPI-amoxicillin-clarithromycin and base their claim on a recent systematic review.4 However, this review has several relevant limitations: First, the…

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Revisiting the performance of cyst fluid carcinoembryonic antigen as a diagnostic marker for pancreatic mucinous cysts: a comprehensive 20-year institutional review

Objective
Elevated pancreatic cyst fluid carcinoembryonic antigen (CEA) has been routinely used to classify mucinous cysts. This study incorporates original data that established the CEA ≥192 ng/mL threshold with over 20 years of additional data and reassesses the diagnostic performance of CEA for differentiating mucinous from non-mucinous cysts.

Design
1169 pancreatic cysts (1999–2021) with CEA results were identified. 394 cases had histological confirmation as the diagnostic standard. Additionally, 237 cysts without histological confirmation demonstrated KRAS, GNAS, or RNF43 mutations by molecular testing and were combined with the histologically confirmed cysts for separate analysis on a total cohort of 631 cysts.

Results
Median CEA was significantly higher in mucinous cysts (323.9 ng/mL, n=314) versus non-mucinous cysts (204.6 ng/mL, n=80) (p

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Blood-based colorectal cancer screening in an integrated health system: a randomised trial of patient adherence

Objective
We evaluated whether people who had not completed a faecal immunochemical test (FIT) for colorectal cancer (CRC) screening would complete a blood-based testing option if offered one during health encounters. Blood-based screening tests for CRC could add to the total number of people screened for CRC by providing another testing alternative.

Design
Study participants were patients aged 45–75 years at a large, integrated health system who were offered but did not complete an FIT in the prior 3–9 months and were scheduled for a clinical encounter. Individuals were randomised (1:1) to be offered a commercially available CRC blood test (Shield, Guardant Health) versus usual care. We compared 3-month CRC screening proportions in the two groups.

Results
We randomised 2026 patients; 2004 remained eligible following postrandomisation exclusions (1003 to usual care and 1001 to blood draw offer; mean age: 60, 62% female, 80% non-Hispanic white). Of the 1001 allocated to the blood test group, 924 were recruited following chart-review exclusions; 548 (59.3%) were reached via phone, of which 280 (51.1%) scheduled an appointment with the research team. CRC screening proportions were 17.5 percentage points higher in the blood test group versus usual care (30.5% vs 13.0%; OR 2.94, 95% CI 2.34 to 3.70; p

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Impacts of armed conflicts on tuberculosis burden and treatment outcomes: a systematic review

Objectives
This systematic review aimed to summarise existing literature on the impacts of armed conflicts on tuberculosis burden and treatment outcomes.

Design
A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

Data sources
PubMed, Web of Science, Cumulative Index to Nursing and Allied Health Literature Plus, Scopus, ScienceDirect, Embase and medRxiv.

Data extraction and synthesis
Three reviewers independently screened, selected eligible studies and extracted data. A narrative review was undertaken to summarise the findings qualitatively.

Results
Eleven studies were included in this review, reporting on tuberculosis incidence rates, prevalence and treatment outcomes, including mortality. Overall, the impact of armed conflicts on case notifications was variable. Six studies reported overall increases in tuberculosis case notifications following the onset of conflicts, while three studies reported overall decreases in tuberculosis case notifications. Factors, including limited access to healthcare services, challenges in surveillance and laboratory confirmation, the destruction of health systems and incapacitating the healthcare workforce, contributed to a decrease in the number of notified cases. The higher tuberculosis notification in some of the studies could be attributed to the disruption of tuberculosis prevention and control programmes as well as increased socioeconomic deprivation, including malnutrition, mass migration, poor living conditions and overcrowding that are worsened during conflicts. Armed conflicts without effective interventions were associated with worse tuberculosis treatment outcomes, including lower proportions of people with treatment success and higher proportions of people with loss to follow-up, mortality and treatment failure. However, implementing various interventions in conflict settings (such as establishing a National Tuberculosis Control Programme) led to higher tuberculosis notification rates and treatment success.

Conclusion
The impact of armed conflicts on tuberculosis notification is complex and is influenced by multiple factors. The findings of this review underscore the importance of concerted efforts to control tuberculosis in conflict settings using available resources.

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Meta-analysis on inflammation and autonomic nervous system of coronary heart disease combined with depression

Objectives
This meta-analysis aimed to explore the association between inflammatory factors, heart rate variability (HRV) and the coexistence of coronary heart disease (CHD) and depression.

Design
Systematic review and meta-analysis. Complying with the Meta-analysis Of Observational Studies in Epidemiology statement.

Data sources
We searched PubMed, Web of Science and EMBASE for the data from the inception date to 16 March 2023.

Eligibility criteria
We included cross-sectional and cohort studies with inclusion criteria: (1) patients with CHD; (2) depression measurement and (3) including inflammatory factors or cardiac biomarkers or HRV.

Data extraction and synthesis
Two authors searched the databases independently. The effect estimates and heterogeneity were synthesised by Review Manager V.5.3. Sensitivity analysis and publication bias were analysed by STATA software. The quantitative synthesis outcomes were presented by mean difference (MD) or standard MD (SMD) with 95% CI.

Results
By searching the databases, we identified a total of 6750 articles. There were 22 articles left after selection, including 6344 participants. This meta-analysis indicated that patients with CHD with depression had higher levels of C reaction protein (CRP) (SMD 0.50, 95% CI (0.19 to 0.81), p=0.001), high-sensitivity C reactive protein (hs-CRP) (SMD 0.28, 95% CI (0.07 to 0.48), p=0.008), IL-6 (SMD 0.49, 95% CI (0.05 to 0.92), p=0.03) and a lower level of the mean RR interval and the SD of all RR intervals (SMD –0.64, 95% CI (–1.11 to –0.17), p=0.008), SD of the 5 min averages of all normal RR intervals (MD –12.77 ms, 95% CI (–21.20 to –4.33), p=0.003), overage of the SD of all normal RR intervals for each 5 min segment (MD –13.83 ms, 95% CI (–15.94 to –11.72), p50 ms (pNN50) (SMD –0.86, 95% CI (–1.41 to –0.31), p=0.002), than those without depression.

Conclusions
This study underscores the association between elevated CRP, hs-CRP, IL-6 and lower HRV in patients with CHD with depression. It emphasises the importance of clinicians assessing CRP, hs-CRP, IL-6 and HRV in patients with CHD to potentially identify depressive conditions.

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Evaluations of virtual exercise programmes for adults with mobility limitations: a scoping review protocol incorporating an equity lens to inform the development of strategies to optimise participation of under-represented groups

Introduction
For individuals with mobility limitations, virtual exercise programmes can address the challenges of in-person participation in community exercise programmes. A synthesis of studies of virtual exercise programmes targeting mobility limitations provided outside of conventional rehabilitation services and strategies used to optimise equitable access and inclusivity in these programmes is lacking. We aim to characterise evaluations of virtual exercise programmes for adults with mobility limitations, and the nature of and extent to which equity, diversity and inclusion considerations are integrated in the research process.

Methods and analysis
A scoping review following a six-stage methodological framework, including a consultation exercise, is proposed. A comprehensive strategy will be used to search Medline, Embase, PEDro, CINAHL and Scopus to identify peer-reviewed studies evaluating virtual exercise programmes for adults with mobility limitations living in the community. Three trained reviewers will select studies independently. Data (eg, study methodology, programme structure and content, participant characteristics) will be extracted using a standardised form, and collated and summarised using quantitative and qualitative methods. The PROGRESS-Plus and International Classification of Functioning, Disability and Health frameworks will be used to classify participant characteristics and study outcomes, respectively. During the consultation exercise, key knowledge users, including exercise participants, programme providers and coordinators, and members of community organisations for persons living with disabilities and under-represented groups, will be asked to provide insights regarding the applicability of review findings. A directed content analysis of data from the consultation exercise will be performed.

Ethics and dissemination
The research ethics board at the University of Toronto approved the consultation exercise. Findings will be disseminated through peer-reviewed publications and conference presentations. Findings will enhance understanding of current research evaluating virtual exercise programmes and inform future research and strategies for promoting equitable access and outcomes for individuals with mobility limitations.

Registration details
https://doi.org/10.17605/OSF.IO/X5JMA.

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Prevalence of metabolic syndrome in patients with inflammatory bowel disease: a systematic review and meta-analysis

Objectives
Patients with inflammatory bowel disease (IBD) may experience comorbidities involving metabolic syndrome (MetS). However, this association remains controversial. Our objective was to estimate the prevalence of MetS in patients with IBD and assess whether MetS is more strongly associated with ulcerative colitis (UC) or Crohn’s disease (CD).

Design
Systematic review and meta-analysis.

Data sources
PubMed, Cochrane Library, Web of Science, EMBASE and MEDLINE were searched from their inception to July 2022.

Eligibility criteria
Observational studies reporting data regarding the rate of comorbid MetS among patients with IBD and published in English.

Data extraction and synthesis
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses and the Meta-analysis of Observational Studies in Epidemiology reporting guidelines were followed. Pooled prevalence, ORs and 95% CIs were calculated using random-effects models. The Newcastle-Ottawa Scale and the Agency for Healthcare Research and Quality checklist were used. Heterogeneity, sensitivity and stratified analyses were performed using R (V.4.2.1).

Results
11 eligible studies involving 2501 patients were included. Of these studies, four reported MetS prevalence separately by IBD phenotype, and only one contained a non-IBD comparison group. Overall, the methodological quality of the included studies was moderate. The pooled prevalence of MetS in IBD was 19.4% (95% CI 15.1% to 23.8%), with a moderate heterogeneity (I2=51.8%, Cochrane Q statistic=12.4, p=0.053). Stratified analyses demonstrated that the aggregate estimate of comorbid MetS was significantly higher in UC than in CD (38.2% vs 13.6%, 2=4.88, p=0.03). We found a positive association between MetS and UC compared with CD (OR=2.11, 95% CI 1.19 to 3.74, p=0.01). Additionally, four studies identified that higher age was a risk factor associated with the development of MetS.

Conclusions
MetS is not rare in IBD, especially in UC. However, longitudinal studies are needed to further clarify the relationship between IBD and MetS.

PROSPERO registration number
CRD42022346340.

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University staff perspectives on determinants of high-quality health professions student placements in regional, rural and remote Australia: protocol for a mixed-method study

Introduction
In rural areas, work-integrated learning in the form of health student placements has several potential benefits, including contributing to student learning, enhancing rural health service capacity and attracting future rural health workforce. Understanding what constitutes a high-quality rural placement experience is important for enhancing these outcomes. There is no current standardised definition of quality in the context of rural health placements, nor is there understanding of how this can be achieved across different rural contexts. This study is guided by one broad research question: what do university staff believe are the determinants of high-quality health professions student placements in regional, rural and remote Australia?

Methods and analysis
This study will adopt a convergent mixed-method design with two components. Component A will use explanatory sequential mixed methods. The first phase of component A will use a survey to explore determinants that contribute to the development of high-quality health student placements from the perspective of university staff who are not employed in University Departments of Rural Health and are involved in the delivery of health student education. The second phase will use semistructured interviews with the same stakeholder group (non-University Department of Rural Health university staff) to identify the determinants of high-quality health student placements. Component B will use a case study Employing COnceptUal schema for policy and Translation Engagement in Research mind mapping method to capture determinants that contribute to the development of high-quality health student placements from the perspective of University Department of Rural Health university staff.

Ethics and dissemination
The University of Melbourne Human Ethics Committee approved the study (2022-23201-33373-5). Following this, seven other Australian university human research ethics committees provided external approval to conduct the study. The results of the study will be presented in several peer-review publications and summary reports to key stakeholder groups.

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Impact of the design of adult mental health inpatient facilities on healthcare staff: a mixed methods systematic review

Objectives
Mental health inpatient facilities are increasingly focusing on creating therapeutic, person-centred care environments. However, research shows that this focus may have unintended consequences for healthcare staff. Designs that do not pay attention to staff needs may risk contributing to stress, burnout, job dissatisfaction and mental exhaustion in the work environment. This systematic review aims to identify and synthesise current research on the design factors of adult mental health inpatient facilities that impact healthcare staff.

Design
A mixed method systematic review was conducted to search for empirical, peer-reviewed studies using the databases CINAHL, Embase, PsycINFO, PubMed and Web of Science from their inception up to 5 September 2023. The Joanna Briggs Institute’s critical appraisal checklists were used to assess the methodological quality of the eligible studies. Data were extracted and grouped based on the facility design factors.

Results
In our review, we included 29 peer-reviewed empirical studies that identified crucial design factors impacting healthcare staff in adult mental health inpatient facilities. Key factors included layouts providing optimal visibility, designated work and respite areas, and centrally located nursing stations. Notably, mixed perceptions regarding the benefits and challenges of open and glass-enclosed nursing stations suggest areas requiring further research. Facilities in geographically remote locations also emerged as a factor influencing staff dynamics. Additionally, although only supported by a limited number of studies, the significance of artwork, sensory rooms for respite, appropriate furniture and equipment, and access to alarms was acknowledged as contributory factors.

Conclusion
Through the synthesis of existing research, this review identified that the design of mental health facilities significantly impacts staff well-being, satisfaction, performance and perception of safety. Concluding that, in order to create a well-designed therapeutic environment, it is essential to account for both service users and staff user needs.

PROSPERO registration number
CRD42022368155.

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Self-management needs, strategies and support for sickle cell disease in developing countries: a scoping review protocol

Introduction
Sickle cell disease (SCD) poses a significant global health burden, particularly affecting individuals in developing countries with constrained healthcare resources. While research on self-management in the context of SCD is emerging, it has predominantly focused on primary studies, and there is a notable dearth of evidence synthesis on SCD self-management in developing countries. This scoping review aims to identify and map self-management needs of individuals living with SCD, the strategies they employed to meet those needs, and the support systems available to them.

Methods and analysis
The review will be conducted following the Arksey and O’Malley’s (2005) 29 framework to comprehensively examine the landscape of SCD self-management research. Searches will be performed in PubMed, Scopus, Embase and Dimensions AI, with additional searches in other databases and grey literature. Indexed literature published in English from inception to January 2024 will be included. Reference list from included studies will also be searched manually. Two teams will be constituted to independently screen titles, abstracts and full text against the eligible criteria. Data will be extracted from included studies onto a customised data extraction form.

Ethics and dissemination
Ethical approval is not required for this review due to the fact that it synthesises information from available publications. The findings will be disseminated through publication in a peer-reviewed journal. Also, the findings will possibly be presented at relevant international and national conferences. This protocol has already been registered with the Open Science Framework. The study characteristics such as design and setting will be descriptively analysed and presented as graphs, tables and figures. Thematic analysis will also be conducted based on the study objectives and presented as a narrative summary.

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Scoping review protocol of post-traumatic growth (PTG) in Korean cancer survivors

Introduction
Cancer, a life-threatening chronic disease, is the leading cause of death in Korea, accounting for 27% of all deaths in 2020. Due to advancements in medical technology and early detection of cancer in Korea, the 5-year relative survival rate reached 70.7% (2015–2019), highlighting remarkable progress over the past decades. Although cancer has been seen as a traumatic event, cancer survivors also go through a subjective process of self-maturation, which is called post-traumatic growth (PTG). Because research on PTG among Korean cancer survivors has not been systematically synthesised, a scoping review on this topic will provide a better understanding of the positive psychological changes that occur as a patient moves through the illness trajectory of cancer from a Korean cultural perspective. The purpose of this study was to describe the protocol of a scoping review regarding PTG in Korean cancer survivors.

Methods and analysis
The scoping review framework suggested by Arksey and O’Malley and the manual refined by the Joanna Briggs Institute for scoping reviews will be used with the six framework guidelines developed by Levac et al. Searched databases will include Ovid-MEDLINE, PubMed, Embase, CINAHL, Cochrane Library and PsycInfo, as well as Korean databases, examining all articles published between 2012 and 2023 in Korean or English on PTG in Korean cancer survivors. Extracted data will be collated, charted and summarised.

Ethics and dissemination
Because the scoping review methodology undertakes a secondary analysis of collected data from previous research studies, this study does not require ethical approval. The results of this scoping review will be disseminated through presentations at conferences and publication in a scientific journal.

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Interventions in adult patients with multimorbidity in low-income and middle-income countries: protocol for a mixed-methods systematic review

Introduction
Multimorbidity, the coexistence of two or more chronic conditions in the same individual, is a major public health problem in low-income and middle-income countries (LMICs). The use of single-disease guidelines contributes to polypharmacy, fragmented care and increased treatment burden. Health systems in LMICs are very different from those in high-income countries, and adapting interventions from one to the other may not be feasible. This review aims to systematically present the current evidence for interventions for multimorbidity in the LMIC setting.

Methods and analysis
In this mixed-methods systematic review, we will include all studies of interventions for the care of adults ( >18 years of age) with multimorbidity (defined as the presence of two or more chronic illnesses in an individual) in any healthcare organisation (primary, secondary or tertiary care) in an LMIC (as defined by the World Bank), published between 2000 and March 2023. All primary study designs will be included. Studies reported in languages other than English and those describing interventions classified as ‘financial’ or ‘governance arrangement’ according to the Cochrane Effective Practice and Organisation of Care classification will be excluded. MEDLINE, PubMed, Cochrane Library, TRIP, SCOPUS and the 3ie databases will be searched. The titles will be screened by one author, and two authors will independently screen all included abstracts and full texts. A third author will resolve conflicts at every stage. Studies will be reviewed for quality of evidence using appropriate tools. Epidemiological, intervention and outcome data will be extracted and summarised. Outcomes of interest for LMICs defined by the Global Alliance for Chronic Diseases research group will be analysed. Subgroup analysis according to study types and study settings will be done.

Ethics and dissemination
No ethics approval is required for this systematic review. Results will be disseminated through publication in an open-access journal and presentation at conferences.

PROSPERO registration number
CRD42023391897.

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Sarcopenia in systemic sclerosis: prevalence and impact–a systematic review and meta-analysis

Objective
This review aims to provide an estimate of sarcopenia prevalence and its impact on clinical characteristics in patients with systemic sclerosis (SSc).

Design
Systematic review and meta-analysis.

Data sources
Embase, Medline, Web of Science and the Cochrane Central Register of Controlled Trials were systemically searched from inception to 24 May 2023.

Eligibility criteria for selecting studies
We included observational studies that reported the prevalence of sarcopenia in patients with SSc.

Data extraction and synthesis
Two reviewers independently performed study selection and data extraction using standardised methods. Risk of bias was assessed using the Agency for Healthcare Research and Quality Scale and the Newcastle–Ottawa Scale. Meta-analysis was conducted using random effects models.

Results
A total of 4583 articles were screened and 9 studies with data from 815 patients were included in the analysis (8 cross-sectional studies and 1 retrospective cohort study). The overall prevalence of sarcopenia in patients with SSc was 22% (95% CI 17% to 28%). Patients with SSc with sarcopenia had a poorer quality of life (mean difference –12.02; 95% CI –19.11 to –4.93) and higher C reactive protein (CRP) levels (standardised mean difference 0.67; 95% CI 0.35 to 1.00).

Conclusions
Sarcopenia is common in patients with SSc. Patients with SSc with sarcopenia had a worse quality of life and higher CRP levels, based on our findings. Given the detrimental impact of sarcopenia on quality of life, future efforts aimed at early identification of sarcopenia in the clinical assessment of patients with SSc may have significance.

PROSPERO registration number
CRD42022368326.

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