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High systolic blood pressure (SBP) is a major risk factor for ischemic heart disease (IHD), the leading cause of death worldwide. Using data from published observational studies and controlled trials, we estimated the mean SBP–IHD dose–response function and burden of proof risk function (BPRF), and we calculated a risk outcome score (ROS) and corresponding star rating (one to five). We found a very strong, significant harmful effect of SBP on IHD, with a mean risk—relative to that at 100 mm Hg SBP—of 1.39 (95% uncertainty interval including between-study heterogeneity 1.34–1.44) at 120 mm Hg, 1.81 (1.70–1.93) at 130 mm Hg and 4.48 (3.81–5.26) at 165 mm Hg. The conservative BPRF measure indicated that SBP exposure between 107.5 and 165.0 mm Hg raised risk by 101.36% on average, yielding a ROS of 0.70 and star rating of five. Our analysis shows that IHD risk was already increasing at 120 mm Hg SBP, rising steadily up to 165 mm Hg and increasing less steeply above that point. Our study endorses the need to prioritize and strengthen strategies for screening, to raise awareness of the need for timely diagnosis and treatment of hypertension and to increase the resources allocated for understanding primordial prevention of elevated blood pressure. A systematic review using the burden of proof meta-analytic method found a significant harmful effect between high systolic blood pressure and ischemic heart disease.

Characterizing the potential health effects of exposure to risk factors such as red meat consumption is essential to inform health policy and practice. Previous meta-analyses evaluating the effects of red meat intake have generated mixed findings and do not formally assess evidence strength. Here, we conducted a systematic review and implemented a meta-regression—relaxing conventional log-linearity assumptions and incorporating between-study heterogeneity—to evaluate the relationships between unprocessed red meat consumption and six potential health outcomes. We found weak evidence of association between unprocessed red meat consumption and colorectal cancer, breast cancer, type 2 diabetes and ischemic heart disease. Moreover, we found no evidence of an association between unprocessed red meat and ischemic stroke or hemorrhagic stroke. We also found that while risk for the six outcomes in our analysis combined was minimized at 0 g unprocessed red meat intake per day, the 95% uncertainty interval that incorporated between-study heterogeneity was very wide: from 0–200 g d −1 . While there is some evidence that eating unprocessed red meat is associated with increased risk of disease incidence and mortality, it is weak and insufficient to make stronger or more conclusive recommendations. More rigorous, well-powered research is needed to better understand and quantify the relationship between consumption of unprocessed red meat and chronic disease. Using the burden of proof analytical tool, a meta-analysis found weak or no evidence of associations between unprocessed red meat consumption and increased risk of six cardiometabolic disease and cancer outcomes.

Despite a gradual decline in smoking rates over time, exposure to secondhand smoke (SHS) continues to cause harm to nonsmokers, who are disproportionately children and women living in low- and middle-income countries. We comprehensively reviewed the literature published by July 2022 concerning the adverse impacts of SHS exposure on nine health outcomes. Following, we quantified each exposure–response association accounting for various sources of uncertainty and evaluated the strength of the evidence supporting our analyses using the Burden of Proof Risk Function methodology. We found all nine health outcomes to be associated with SHS exposure. We conservatively estimated that SHS increases the risk of ischemic heart disease, stroke, type 2 diabetes and lung cancer by at least around 8%, 5%, 1% and 1%, respectively, with the evidence supporting these harmful associations rated as weak (two stars). The evidence supporting the harmful associations between SHS and otitis media, asthma, lower respiratory infections, breast cancer and chronic obstructive pulmonary disease was weaker (one star). Despite the weak underlying evidence for these associations, our results reinforce the harmful effects of SHS on health and the need to prioritize advancing efforts to reduce active and passive smoking through a combination of public health policies and education initiatives. A meta-analysis using the Burden of Proof method reported consistent evidence supporting harmful associations between exposures to secondhand smoke and nine health outcomes.

As a leading behavioral risk factor for numerous health outcomes, smoking is a major ongoing public health challenge. Although evidence on the health effects of smoking has been widely reported, few attempts have evaluated the dose–response relationship between smoking and a diverse range of health outcomes systematically and comprehensively. In the present study, we re-estimated the dose–response relationships between current smoking and 36 health outcomes by conducting systematic reviews up to 31 May 2022, employing a meta-analytic method that incorporates between-study heterogeneity into estimates of uncertainty. Among the 36 selected outcomes, 8 had strong-to-very-strong evidence of an association with smoking, 21 had weak-to-moderate evidence of association and 7 had no evidence of association. By overcoming many of the limitations of traditional meta-analyses, our approach provides comprehensive, up-to-date and easy-to-use estimates of the evidence on the health effects of smoking. These estimates provide important information for tobacco control advocates, policy makers, researchers, physicians, smokers and the public. A meta-analysis using the Burden of proof method reported consistent evidence supporting harmful associations between smoking and 28 different health outcomes.

Chewing tobacco use poses serious health risks; yet it has not received as much attention as other tobacco-related products. This study synthesizes existing evidence regarding the health impacts of chewing tobacco while accounting for various sources of uncertainty. We conducted a systematic review and meta-analysis of chewing tobacco and seven health outcomes, drawing on 103 studies published from 1970 to 2023. We use a Burden of Proof meta-analysis to generate conservative risk estimates and find weak-to-moderate evidence that tobacco chewers have an increased risk of stroke, lip and oral cavity cancer, esophageal cancer, nasopharynx cancer, other pharynx cancer, and laryngeal cancer. We additionally find insufficient evidence of an association between chewing tobacco and ischemic heart disease. Our findings highlight a need for policy makers, researchers, and communities at risk to devote greater attention to chewing tobacco by both advancing tobacco control efforts and investing in strengthening the existing evidence base. While the number of chewing tobacco users is increasing in many countries, it is often under-emphasized in tobacco control. Here, the authors show that chewing tobacco is a risk factor for major causes of disease burden, including stroke and various cancers, meriting future research and policy attention.

Cohort and case-control data have suggested an association between low to moderate alcohol consumption and decreased risk of ischemic heart disease (IHD), yet results from Mendelian randomization (MR) studies designed to reduce bias have shown either no or a harmful association. Here we conducted an updated systematic review and re-evaluated existing cohort, case-control, and MR data using the burden of proof meta-analytical framework. Cohort and case-control data show low to moderate alcohol consumption is associated with decreased IHD risk – specifically, intake is inversely related to IHD and myocardial infarction morbidity in both sexes and IHD mortality in males – while pooled MR data show no association, confirming that self-reported versus genetically predicted alcohol use data yield conflicting findings about the alcohol-IHD relationship. Our results highlight the need to advance MR methodologies and emulate randomized trials using large observational databases to obtain more definitive answers to this critical public health question. Alcohol use is commonplace and ischemic heart disease (IHD) the leading cause of death globally, yet their relationship is unclear. Here we show that study type determines whether research finds alcohol reduces IHD risk or is unrelated, arguing for new approaches to settle this critical debate.

Background Family caregivers are essential members of the care team of someone with pancreatic cancer, supporting their physical and psychological needs. Caregivers are often unprepared for this which may cause substantial psychosocial impact. This may be exacerbated by the short life-expectancy and rapid deterioration associated with pancreatic cancer. A scoping review was conducted to identify, from the existing literature, what is currently known about the psychosocial impact of pancreatic cancer on caregivers across the disease trajectory. Methods A Joanna Briggs Institute (JBI) mixed methods scoping review was conducted across four databases (CINAHL, EMBASE, MEDLINE, PsycINFO). All identified citations were uploaded to Covidence, and were screened independently by two reviewers. Data were extracted and synthesised following a deductive approach guided by ‘The Cancer Family Caregiving Experience’ model (Fletcher et al., 2012). Results 42 studies were included: 22 qualitative, 15 quantitative, 5 mixed methods. Results of the included studies were collated into the proposed constructs of Fletcher et al.’s (2012) model: primary stressors, secondary stressors, appraisal, cognitive-behavioural responses, health and wellbeing outcomes, as well as the influence of disease trajectory and contextual factors. The literature highlighted pancreatic cancer caregivers experienced stress related to caregiving activities, disruptions in their daily life and family relationships, high levels of unmet need, and poorer quality of life compared to other cancer caregivers. They were also at increased risk for various psychiatric disorders and reported a persistent lack of support which exacerbated the psychosocial impact. Conclusions Pancreatic cancer caregivers experience negative psychosocial impacts, exacerbated by the disease’s trajectory. Feelings of a lack of support were reflected throughout the included literature and emphasise the need for future research into how pancreatic cancer caregivers may be best supported, and sign-posted to existing support, to minimise the substantial psychosocial impact they may experience.

Background Pancreatic cancer is an aggressive disease with most cases diagnosed at an advanced stage resulting in low survival rates. Family members often take on a role of supporting patients’ needs. Families tend to be unprepared for this and experience high levels of unmet needs and substantial impacts to their own wellbeing, heightened by the rapid deterioration and short life expectancy associated with pancreatic cancer. Aim The proposed study aims to explore the supportive care needs and associated psychosocial impact of pancreatic cancer on family members, and the role of support services in supporting these families. Methods A sequential explanatory mixed methods design will be utilised. Data collection will consist of three phases: (1) Survey of affected family members to explore their supportive care needs and psychological wellbeing; (2) Semi-structured interviews to explore the lived experiences of family members across the disease trajectory, their psychosocial adjustment, and their perceptions of support services; (3) Focus groups with support services providers to explore their experiences in providing support to affected families. Discussion By combining quantitative and qualitative approaches, this research aims to provide a comprehensive understanding of the challenges and opportunities in providing psychosocial support to families affected by pancreatic cancer, ultimately enhancing their quality of life during and after the cancer journey. The findings may help to inform the development and enhancement of support programs, tailored to meet the specific needs of affected families.

Few auditory functions are as important or as universal as the capacity for auditory spatial awareness (e.g., sound localization). That ability relies on sensitivity to acoustical cues—particularly interaural time and level differences (ITD and ILD)—that correlate with sound-source locations. Under nonspatial listening conditions, cortical sensitivity to ITD and ILD takes the form of broad contralaterally dominated response functions. It is unknown, however, whether that sensitivity reflects representations of the specific physical cues or a higher-order representation of auditory space (i.e., integrated cue processing), nor is it known whether responses to spatial cues are modulated by active spatial listening. To investigate, sensitivity to parametrically varied ITD or ILD cues was measured using fMRI during spatial and nonspatial listening tasks. Task type varied across blocks where targets were presented in one of three dimensions: auditory location, pitch, or visual brightness. Task effects were localized primarily to lateral posterior superior temporal gyrus (pSTG) and modulated binaural-cue response functions differently in the two hemispheres. Active spatial listening (location tasks) enhanced both contralateral and ipsilateral responses in the right hemisphere but maintained or enhanced contralateral dominance in the left hemisphere. Two observations suggest integrated processing of ITD and ILD. First, overlapping regions in medial pSTG exhibited significant sensitivity to both cues. Second, successful classification of multivoxel patterns was observed for both cue types and—critically—for cross-cue classification. Together, these results suggest a higher-order representation of auditory space in the human auditory cortex that at least partly integrates the specific underlying cues.