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Causes, associated exposures, and outcomes of cirrhosis and hepatocellular carcinoma in Malawi: an observational cohort and case–control study
Get PDFBackground: African countries have the highest age-standardised mortality from liver disease. We studied patients with cirrhosis and hepatocellular carcinoma in Malawi to ascertain the causes, associated exposures, and outcomes after discharge, and identify opportunities for intervention strategies.
Methods: In this case–control cohort study, we recruited patients aged 16 years or older who met the study definitions for cirrhosis or hepatocellular carcinoma from the Queen Elizabeth Central Hospital in Blantyre, Malawi. In the cirrhosis group, we excluded patients with a liver stiffness greater than 12 kPa if a cause of potential false elevation of liver stiffness was identified and a liver ultrasound did not show signs of cirrhosis; people with extrapulmonary tuberculosis or other non-hepatic causes of ascites; and pregnant people. In the hepatocellular carcinoma group, we excluded those with an extrahepatic malignancy or ultrasound features consistent with liver metastases, pregnant people, and indeterminate lesions as determined by consultant radiologists on serial ultrasounds. Research nurses identified potential participants on medical and surgical wards, the medical outpatient clinic, and endoscopy unit, using systematic case notes review and clinician referral during weekdays. Patients were followed up for 6 months. A community sample was recruited from the catchment area of the hospital to estimate the general population prevalence of diseases and exposures potentially associated with liver disease. For hepatitis B and C, we conducted a serological survey in individuals aged 16 years or older who were randomly selected from a census, and we randomly selected a proportion of individuals who were HBsAg positive or HBsAg negative to estimate the general population prevalence of HIV, alcohol, smoking, diabetes, hepatitis D and E, and autoimmune hepatitis serological markers. We estimated population attributable fractions (PAFs) for cirrhosis and hepatocellular carcinoma using community controls and the serological survey. PAFs were estimated from logistic regression models adjusted for age and sex, using the Bruzzi method with percentile bootstrap confidence intervals.
Findings: Between Nov 1, 2017, and April 30, 2019, we prospectively screened 708 patients and enrolled 138 diagnosed with cirrhosis and 78 diagnosed with hepatocellular carcinoma. Patients had a median age of 40 years (IQR 35–51), 134 (62%) were male, and 82 (38%) were female. In those with hepatocellular carcinoma, median tumour size was 13·2cm (10·2–17·3) and median survival was 40 days (95% CI 30–51). The community sample comprised 3258 individuals with hepatitis B and 1661 with hepatitis C identified from the serological survey, and 120 individuals negative for HBsAg and 94 people who were HBsAg positive from the serological survey to estimate the general population prevalence of HIV, alcohol, smoking, diabetes, hepatitis D and E, and autoimmune hepatitis serological markers. At 6 months, 83 (60%) of 130 patients with cirrhosis and six (8%) of 78 patients with hepatocellular carcinoma were still alive. Hepatitis B was the main attributable cause of cirrhosis (PAF 25·3% [17·5–33·3]) and hepatocellular carcinoma (73·1% [62·6–82·9]). HIV was the second leading attributable exposure associated with cirrhosis (22·2% [12·2–32·2]) and hepatocellular carcinoma (18·0% [4·8–30·9]); the association persisted after adjusting for hepatitis B virus co-infection. For hepatocellular carcinoma (but not cirrhosis), smoking (23·6% [8·9 to 37·2]) and alcohol (14·5 [–0·2 to 28·4]) were secondary attributable exposures. Autoimmune hepatitis (five [4%] patients), primary biliary cholangitis (four [3%] patients), and hepatitis C (two [1%] patients) were uncommon causes of cirrhosis, and no patients in either group had hepatitis D or E viraemia.
Interpretation: Hepatitis B is the leading cause of cirrhosis and hepatocellular carcinoma in Malawi. HIV was diagnosed at a much higher rate among patients with cirrhosis and hepatocellular carcinoma than community controls; it is uncertain whether the relationship is causal or influenced by confounding. Alcohol and smoking are modifiable exposures associated with hepatocellular carcinoma. Hepatocellular carcinoma and cirrhosis are diagnosed at an advanced stage, with a poor prognosis. Community screen-and-treat programmes for hepatitis B could substantially reduce liver-related mortality in this region
AI surveillance in education: unpacking ethical dilemmas and the snake-oil promises of AI-infused technosolutionism
Get PDFThis chapter uses a collaborative swarm writing method to critically examine the ethical implications of the increasing integration of AI surveillance technologies within educational settings, including proctoring software, classroom monitoring tools, and behavioral analytics. Our swarm approach reflects diverse perspectives on this complex issue. It unpacks how AI surveillance reduces multifaceted students and faculty to data points, disproportionately targeting marginalized learners and misreading neurodivergent behaviors. The authors argue that this ghostly algorithmic gaze transforms academic spaces into mechanized surveillance states, subordinating human agency to machine logic and potentially diminishing the quality of the learning experience. The chapter critiques the snake’s oil sales pitch of AI-infused technosolutionist discourse and foregrounds concerns regarding the erosion of student and lecturer autonomy, the alteration of student-lecturer relationships and the erosion of trust, the normalization of surveillance, and the amplification of existing inequalities and biases through algorithmic processes. We conclude by emphasizing the need for educators and institutions to resist the managerial reductionism driven by corporate digital platforms and to foster a learning environment that amplifies human potential rather than restricting it through pervasive surveillance
A randomized clinical trial of mindfulness training versus a health promotion program: Impact on cognitive and mental health in older immigrants
Get PDFBackground: Mindfulness-based stress reduction (MBSR) has shown benefits for cognition and stress relief. Enhancing these functions may have a protective role in vulnerable populations, particularly older immigrants who face a higher risk of neurodegenerative disease. However, whether MBSR can have positive effects on cognitive and affective functions in these populations remains understudied. This trial compared the effects of MBSR with a health promotion program (HPP) in older immigrants. Methods: In this single-center, randomized, double-blind controlled trial, 151 Portuguese-speaking older immigrants (≥55 years old) residing in Luxembourg were screened and 89 participants (age range: 55–80, M age: 62.58 years ± 6.08, 72 % women) were randomized to 2-month weekly group interventions of either MBSR (n = 44) or HPP (n = 45). Data were collected at three time points: baseline, immediately after the intervention (post- intervention), and at follow-up, conducted one to three months after the intervention. Executive functioning measures, including Letter-Number Sequencing, Trail Making Test, and Stroop color-word, were the main outcomes. Secondary outcomes included general cognitive functioning, cortisol level, heart rate variability, and self- reported affective and mindfulness states. Results: 75 % of participants in the MBSR group and 53 % in the HPP group completed at least one post- assessment. Linear mixed model analyses showed significant time effects in Letter-Number Sequencing (p = .04), as well as reductions in anxiety (p < .01) and perceived stress (p < .01), with no significant group differences or group × time interactions. These improvements were observed from baseline to post-intervention and still persisted at follow-up. Conclusion: Both interventions positively influenced attention, with the most notable improvements observed in anxiety and perceived stress. These findings suggest that group interventions may have the potential to improve cognitive and affective indicators, regardless of their specific content. Despite their diverse goals, the interventions shared procedural features, such as the organization and delivery of the sessions, which may have contributed to the outcomes observed. This underscores the potential value of well-designed group-based programs in cognitive and affective indicators among vulnerable older adults. While further research is needed, our findings point to the relevance of including these interventions within the realm of promoting healthy aging and dementia prevention
Dismantling behavioural weight management interventions: component network meta-analysis of randomised controlled trials and real-world services
No full textBackground: Behavioural weight management interventions (BWMIs) are complex
interventions having several coexisting components designed to facilitate weight loss.
Existing evidence has shown BWMIs to be effective, however, the magnitude of weight
loss varies among programmes. There is value in understanding whether differences
in the intervention components influence the overall effectiveness of the interventions.
The current study is the first attempt to explore the effects of individual components of
interventions using data from both randomised controlled trials (RCTs) and real-world
services (RWSs) based in the UK.
Objective: To deconstruct BWMIs into constituent components and identify the
effectiveness of individual components for weight loss.
Design: A component network meta-analysis of data from RCTs and RWSs.
Setting: RWSs and RCTs based in the UK for weight management in adults.
Participants: Adults over 18 years of age, living in the UK and attending behavioural
weight management interventions in the real-world (n= 76,201) or participating in
RCTs (n= 4,051).
Main outcome measure: Mean change in weight after 12 weeks of active weight loss
sessions.
Methods: Bayesian two-staged component network meta-analysis using an additive
model.
Results: In the analysis of RCTs, significant weight loss was associated with
components tailoring (Mean Difference [MD] = -5.54 kg; 95% Credible Interval [CrI] = -
7.72, -3.35), flexibility in attendance (MD = -3.18 kg; 95% CrI = -4.29, -2.07), and
multimodal referral (MD = -2.57 kg; 95% CrI = -4.89, -0.25). In RWSs, the components
associated with significant weight loss included multimodal referral (MD=-2.01, 95%
CrI =-2.13, -1.88), personalised dietary advice (MD=-1.22, 95% CrI =-1.33, -1.11),
flexibility (MD=-0.41, 95% CrI =-0.47, -0.35), and in person delivery (MD=-0.45, 95%
CrI =-0.52, -0.38). However, co-design (MD = 3.46 kg; 95% CrI = 2.12, 4.82) in RCTs,
and added extras (MD = 0.99 kg; 95% CrI = 0.88, 1.10) and tailoring (MD= 0.33 kg;
95% CrI = 0.27, 0.40) in RWSs were not shown to be effective in short term weight
loss. Conclusions: The findings from this study highlight the importance of understanding
the impact of intervention components such as accessibility, flexibility, tailoring and
dietary advise and in-person delivery in weight loss at 12 weeks. Future research
should consider exploring the component interactions and long-term weight loss for
improved understanding and developing effective programmes
Exploring stakeholder perceptions and priorities related to reducing tick-related public health risks in natural environments of the United Kingdom
Get PDFBackground:
Tick-borne disease (TBD) risks to humans and livestock are increasing rapidly in temperate regions, including the UK, with severe impacts on human and animal health and livelihoods. These threats could be exacerbated by large-scale policy-driven changes to increase woodland area and connectivity, which might increase the abundance of the key tick vector, Ixodes ricinus, and its interactions with people, livestock and wildlife hosts. Environmental interventions have been suggested as potential ecologically friendly options with the propensity to mitigate risk from ticks and TBDs in woodland areas, which are often characterised by high tick-human contact rates. Yet the uptake of these interventions is dependent on their alignment with stakeholders’ land management priorities and attitudes. Effective co-production practices will ensure that the implementation of land-based tick control interventions aligns with stakeholder priorities and are acceptable to society. However, there is limited empirical understanding about the viability and acceptability of land-based interventions to reduce risk from ticks on the ground.
Methods:
Three multi-stakeholder workshops (N = 40 participants), held in Aberdeenshire (Scotland) and New Forest (England) respectively, together with key-informant interviews (N = 18) were used to explore the stakeholders’ perceptions of, and attitudes towards, the potential implementation of land-based tick control interventions.
Results:
Overall, while study participants expressed a general concern about the tick ‘problem’, there were varied perspectives towards implementing potential environmental interventions for tick and deer management. Of the potential interventions identified, deer exclusion measures (e.g. fencing) were perceived negatively as costly and ineffective at scale. Study participants highlighted there is no one-size-fits-all intervention for deer and/or tick management, noting that a combination of interventions is needed to reconcile differing stakeholder priorities and expectations about land management on a landscape scale.
Conclusion:
Altogether, the study highlights the importance of harmonising land-use policies and continuous dialogue between stakeholders to reconcile competing land management objectives
Approaches to economic evaluations of complex interventions in Thailand: a systematic review
Get PDFBackground: Complex interventions (CIs) are multifaceted health interventions that incorporate health, behavioural, social, organisational, and policy modifications at both individual and population levels. Therefore, evaluating the trade-offs between costs and benefits of CIs is challenging. In Thailand, CIs are increasingly being adopted in different settings and contexts. This study aims to synthesise the evidence on methodological approaches employed in economic evaluation of CIs within the Thai context.
Methods: A systematic review of health economic evaluations of CIs in Thailand was conducted. Four databases (EMBASE, MEDLINE, EconLit, and HiTAP) were searched between January 2008 and July 2024. Studies were included if they met the United Kingdom Medical Research Council (MRC) definition for CIs (i.e., multicomponent design, behavioural targeting, expertise and skill requirements, multi-targeted group setting, and flexibility) and reported economic evaluations (cost-benefit, cost-consequence, cost-effectiveness, cost-utility, or cost-minimisation analyses) in Thailand. Non-English language and non-human studies were excluded. Relevant data on intervention types, methodological characteristics, and key findings were extracted and a narrative synthesis was carried out. The quality of included studies was assessed using the CHEERS checklist.
Results: Sixty studies met the eligible criteria, categorised into screening programmes (33%), vaccination programmes (30%), other public health interventions (22%), and treatment and rehabilitation interventions (15%). Model-based cost-utility analysis from a societal perspective with lifetime horizon was the most frequently reported approach, particularly in screening programmes and treatment and rehabilitation interventions. while mid- and short-term horizons were more common for public health and treatment interventions, respectively. None explicitly identified interventions as CIs. However, alignment with MRC guidance was partial with limited use of designs capturing multidirectional, multisector effects, minimal stakeholder engagement, and underuse of advanced modelling techniques. Cost-benefit and cost-consequence analyses were underutilised. Most studies fulfilled the CHEERS criteria, but inconsistent reporting and weak stakeholder involvement indicated methodological gaps.
Conclusion: Economic evaluations of CIs in Thailand have expanded since 2008. Partially adherence to the MRC framework, important gaps remain in comprehensive perspectives, early integration of economic considerations, and the use of advanced modelling techniques. Addressing these areas could enhance the robustness and policy relevance of future evaluations
Differential associations between smoking, e-cigarette use, and diabetes prevalence
Get PDFBackground:
Cigarette smoking is a well-established risk factor for diabetes, but the relationship between e-cigarette use and diabetes remains uncertain. Evidence to date has been drawn almost entirely from North America and Asia, with little information from European populations.
Methods:
We conducted a cross-sectional study of 17,854 adults aged 16 years and older from the 2017, 2018, 2019, and 2021 waves of the nationally representative Scottish Health Survey. Diabetes status was based on self-report of doctor-diagnosed diabetes. Participants were classified into six mutually exclusive categories of smoking and e-cigarette use: never users of either cigarettes or e-cigarettes, ex-smokers (former smokers who never used e-cigarettes), current exclusive cigarette smokers, current exclusive e-cigarette users, current dual users, and former e-cigarette users. Weighted prevalence estimates and survey-weighted binary logistic regression models were used to examine associations, adjusting for age group, sex, education, deprivation quintile, ethnicity, alcohol use, physical activity, and hypertension.
Results:
Diabetes prevalence was highest among ex-smokers (11.3 %, 95 % CI: 10.1–12.5). Prevalence was 5.7 % (95 % CI: 5.2–6.2) among never users of either cigarettes or e-cigarettes, 6.2 % (95 % CI: 4.9–7.9) among current exclusive cigarette smokers, 4.9 % (95 % CI: 3.4–7.1) among current exclusive e-cigarette users, 8.3 % (95 % CI: 5.8–11.8) among current dual users, and 5.1 % (95 % CI: 4.1–6.3) among former e-cigarette users. In adjusted models, ex-smokers had 35 % higher odds of diabetes compared with never users of either cigarettes or e-cigarettes (OR = 1.35, 95 % CI = 1.14–1.60, p < 0.001), whereas current exclusive smokers (OR = 0.78, 95 % CI = 0.58–1.03, p = 0.084), current exclusive e-cigarette users (OR = 0.81, 95 % CI = 0.53–1.22, p = 0.309), current dual users (OR = 1.49, 95 % CI = 0.94–2.38, p = 0.091), and former e-cigarette users (OR = 1.00, 95 % CI = 0.78–1.29, p = 0.973) were not significantly different from never users. Sensitivity analyses restricting ex-smokers to those with ≥5 years since cessation and limiting the sample to adults aged ≥45 years reproduced the same pattern of results.
Conclusions:
In this nationally representative study of Scottish adults, excess diabetes prevalence was observed among ex-smokers, a pattern that may reflect both reverse causation if individuals quit smoking after diagnosis and the lasting metabolic effects of cumulative smoking exposure. Neither current nor former e-cigarette use was associated with diabetes, and the observed variation in prevalence appeared linked to smoking history rather than e-cigarette use. However, because vaping is relatively recent, further longitudinal research is needed to clarify any long-term risks
PixlMap: a generalisable pixel classifier for cellular phenotyping in multiplex immunofluorescence images
Get PDFMultiplexed methods for the detection of protein expression generate extremely data-rich images of intact tissue sections. These images are invaluable for the quantification and analysis of complex biology and biomarker development. However, their interpretation presents a considerable analytical challenge. Cell segmentation from images is a key bottleneck and a major focus of research activity in artificial intelligence. Most current methods depend initially on the use of a nuclear counterstain to identify nuclear boundaries, which is a relatively straightforward task. The cellular boundary is then assigned either by expansion of the nuclear outline, or by the use of membrane or cytoplasm-specific stains to delineate cell boundaries, or by some combination of the two. The task is critical, as inaccurate segmentation leads to information loss and data contamination from neighbouring cells. Increasingly sophisticated methods are being developed to address these issues, but each has its own shortcomings. We present an alternative method which is inspired by the fact that the assignation of a cellular phenotype ‘by eye’ does not depend upon the accurate identification of cell boundaries. We present an easy-to-use deep learning-based cellular phenotyping method which leverages this human capacity to assign phenotypes without segmenting the entire cell, and which can accurately phenotype cells based on nuclear segmentation alone. Using human ground truth annotations of entire cellular regions, we developed a classifier leveraging the U-Net architecture within a commercially available deep learning image analysis platform, but the principle is transferrable to any deep-learning framework. Crucially, training requires only a single example of each compartmental stain (nuclear/cytoplasmic/membranous). The resulting algorithm assigns class identities to cells with nuclear labelling alone, without the need for whole cell expansion. The method is highly novel, broadly generalisable, and comparable in accuracy to intensity-based phenotyping methods, bridging the gap between inaccurate cellular segmentation and accurate phenotype generation
The roles of race and ethnicity vs. awareness and attractiveness in film audiences’ casting preferences
Get PDFFilm industry elites justify racially exclusionary casting practices with the rationale that White audiences prefer to watch White actors. Nevertheless, previous academic research into White audience demand for minority film casting has produced mixed results in testing this claim. Presenting findings from a mixed-method quantitative (n = 1071) and qualitative (n = 25) study, this article examines the relationship between audience race and ethnicity and actor race and ethnicity versus other potential influences on demand, and investigates how film audiences discursively justify their casting preferences. We find that, overall, awareness and perceived attractiveness of an actor remain more important criteria than race and ethnicity when audiences make consumption choices. Nevertheless, racialized assumptions and issues of systemic racism pervade White audiences’ casting rationales, particularly in the way that Eurocentric beauty standards and expectations about what actors should “look like” inflect audience discourses around perceived fit of an actor to a role
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