ALDH2 polymorphism, alcohol intake and the attributable burden of cancer in East Asia: systematic review, meta-analysis, and modeling study.

PURPOSE: To estimate the burden of alcohol-attributable cancer in East Asian populations accounting for aldehyde dehydrogenase-2 (ALDH2) genotype-specific cancer risk and alcohol exposure. METHODS: We conducted a systematic review and meta-analysis of eight databases on cancer risk to derive alcohol dose-response curves by ALDH2 genotype. A simulation-based approach using the Global Burden of Disease (GBD) modeling framework was applied to estimate the population attributable fraction, incidence, and disability-adjusted life-years (DALYs) lost to alcohol-attributable cancer. RESULTS: We included 34 studies (66,655 participants) from China, Japan, and South Korea in the meta-analysis. Alcohol dose-response curves for liver, esophageal, and oral cavity/pharynx cancer showed an increased risk for people with the inactivated ALDH2 genetic polymorphism, resulting in a higher burden of alcohol-attributable cancer compared to GBD estimates. Our methods estimated annual incidence of cancer of 230,177 cases, an underestimate of 69,596 cases compared to GBD estimates. Similarly, total DALYs lost annually were underestimated by 1.20 million. CONCLUSIONS: The burden of liver, esophageal, and oral cavity/pharynx cancer attributable to alcohol is underestimated in populations with the ALDH2 genetic polymorphism when compared to current estimates.

Impact of alcohol taxes on violence in Hong Kong: a population-based interrupted time series analysis.

BACKGROUND: Interpersonal violence is a major public health concern with alcohol use a known risk factor. Despite alcohol taxation being an effective policy to reduce consumption; Hong Kong, contrary to most developed economies, embarked on an alcohol tax reduction and elimination policy. METHODS: To assess the impact of the alcohol tax reductions, we analysed population-based hospitalisation data for assault from the Hong Kong Hospital Authority, and violent and sexual crimes recorded by the Hong Kong Police Force (2004-2018). We conducted an interrupted time series using seasonal autoregressive integrated moving average models on monthly rates. Breakpoints in March 2007 and March 2008 were applied separately. RESULTS: The 2007 tax cut was associated with sustained increases in violence-related hospitalisation rates for 35-49 age group (female: 0.19%, p=0.007; male: 0.22%, p<0.001; overall: 0.16%, p=0.007); and an immediate increase of 51.3% (p=0.005) in the rate of sexual crimes reported. Results for the 35-49 age group after the 2008 tax cut were similar with sustained increases in hospitalisation rates (female: 0.21%, p=0.010; male: 0.23%, p<0.001; overall: 0.17%, p<0.001). The 2008 tax cut was also associated with immediate increases in hospitalisation rates in children (female: 33.1%, p=0.011; male: 49.2%, p<0.001, overall: 31.5%, p=0.007). For both tax cuts, results were insignificant in males and females for other age groups (15-34 and 50+ years). CONCLUSIONS: Both alcohol tax reductions in 2007 and 2008 were in some age groups associated with increases in violence-related hospitalisations and reports of sexual assault even in an environment of low crime.

Anti-tumour necrosis factor-induced skin rashes in inflammatory bowel disease: a systematic review and evidence-based management algorithm.

BACKGROUND: Anti-tumour necrosis factor alpha (anti-TNF) agents are a highly effective treatment for inflammatory bowel disease (IBD). Skin lesions, including psoriasiform, eczematous and lupoid eruptions, may paradoxically result from anti-TNF use and cause significant morbidity leading to discontinuation of therapy. There are no consensus guidelines on the management of these lesions. AIMS: This systematic review considers the existing evidence regarding cutaneous complications of anti-TNF therapy in IBD and the development of an algorithm for management. METHODS: A systematic review was performed by searching Medline (Pubmed) and Embase for articles published from inception to January 2021. The following search terms were used 'anti-tumour necrosis factor alpha', 'infliximab', 'adalimumab', 'certolizumab', 'golimumab', 'inflammatory bowel disease', 'Crohn disease', 'Ulcerative colitis', 'psoriasis', 'psoriasiform', 'dermatitis', 'lupus', 'skin lesion' and 'skin rash'. Reference lists of relevant studies were reviewed to identify additional suitable studies. RESULTS: Thirty-four studies were included in the review. Eczema can generally be managed with topical agents and the anti-TNF can be continued, while the development of lupus requires immediate cessation of the anti-TNF and consideration of alternative immunomodulators. Management of psoriasis and psoriasiform lesions may follow a step-wise algorithm where topical treatments will be trialled in less severe cases, with recourse to an alternative anti-TNF or a switch to an alternative class of biological agent. CONCLUSION: Assessment of anti-TNF skin lesions should be performed in conjunction with a dermatologist and rheumatologist in complex cases. High-quality prospective studies are needed to clarify the validity of these algorithms in the future.

The impact of alcohol pricing policies on public health in Hong Kong, China: A modelling study.

Background: Contrary to most developed economies, Hong Kong has reduced and eliminated taxes on beer and wine over the last 15 years and observed increasing alcohol consumption. Methods: We applied econometric epidemiological modelling to assess the impact of reverting ad valorem taxation to pre-2008 levels (20% on wine and 40% on beer) on consumption and health outcomes. We used 15 years of industry sales and pricing data (2004-2018) to derive 25 own-price and cross-price elasticity estimates. We applied risk functions from the World Health Organization 2018 Global Status Report to assess the impact on 25 alcohol-attributable conditions. Findings: An estimated 616 deaths (91.3% in men) were attributable to alcohol in 2018. Raising taxes to pre-2008 levels is estimated to reduce consumption of pure alcohol consumption by 8.0%, 15.9%, and 31.1%; and reduce alcohol-attributable deaths by 11.6%, 21.8%, and 40.2% assuming 25%, 50% and 100% pass through rates of taxes to consumers. The largest projected decreases in alcohol-attributable mortality in absolute numbers are alcohol abuse, alcohol dependence, and alcoholic psychoses (wholly alcohol-attributable disorders). The largest absolute number of new alcohol-attributable cases in 2018 were hypertension, alcohol dependence and alcohol abuse; which are estimated to be reduced by 31.3%, 34.2%, and 34.3% respectively by raising taxes to pre-2008 levels. The alcohol-attributable health burden and absolute reductions in health harms are far greater in men. Interpretation: Reversing the 2008 alcohol tax reductions is potentially effective in averting the alcohol-attributable health burden and thus mitigate against the avoidable harms of alcohol-related disease. Funding: Health and Medical Research Fund, Food and Health Bureau of the Hong Kong SAR, China [03170067].

The impact of road safety policies in a deregulated alcohol tax environment in Hong Kong: a 15-year time series analysis.

BACKGROUND AND AIMS: Hong Kong reduced beer and wine tax in 2007, eliminated taxes on beer and wine and strengthened drink-driving legislation in 2008, and increased police traffic enforcement after the 2014 social unrest. This study aimed to measure the effects of implementing road safety policies on road traffic harm in the context of deregulated alcohol control policy in Hong Kong. DESIGN: Population-based interrupted time series analysis using seasonal autoregressive integrated moving average (sARIMA) models. Multiple sensitivity analyses were conducted. SETTING: Hong Kong, China and Singapore from January 2004 to December 2019. CASES: A total of 313 728 road traffic injuries in Hong Kong and 163 773 road traffic injuries in Singapore as controls. MEASUREMENTS: Monthly rates of road traffic injuries, non-fatal injuries and serious/fatal injuries from Hong Kong and Singapore Police Force. FINDINGS: The elimination of alcohol taxes and the enactment of road safety legislation in 2008 were associated with immediate reductions in total road traffic injuries of 6.71% (95% CI, 1.99%-11.20%), serious/fatal injuries of 13.80% (95% CI, 1.85%-24.30%) and sustained declines in drink-driving and collisions involving drink-driving. The effects of the 2007 tax reduction were inconclusive. Progressively increasing traffic enforcement was associated with continuous reductions in road traffic injuries by 0.21% per month (95% CI, 0.13%-0.30%), and serious/fatal injuries by 1.10% per month (95% CI, 0.85%-1.35%). Effects at the corresponding timepoints in Singapore did not reach statistical significance; the results were inconclusive regarding confounding effects on both regions. CONCLUSIONS: Despite weakened alcohol control and increased alcohol sales over the same period, road safety policies in Hong Kong are associated with net reductions in road traffic injuries, particularly serious/fatal injuries.

Pre-procedural use of thrombopoietin-receptor agonists in cirrhosis and severe thrombocytopenia: A systematic review and meta-analysis.

BACKGROUND: Severe thrombocytopenia in cirrhosis can preclude invasive procedures. Platelet transfusion is recommended if platelet count pre-procedure is potential alternative to platelet transfusion is thrombopoietin-receptor (TPO) agonists. AIM: Evaluate TPO-agonist efficacy and safety in cirrhotic patients with severe thrombocytopenia undergoing invasive procedures. METHODS: Randomized control trials (RCT) from electronic reference databases were searched from inception till December 2019. PRISMA guidelines were followed. Primary outcome was platelet transfusion avoidance. Secondary outcomes were weighted mean difference (WMD) in platelet count from baseline to pre-procedure and rates of major adverse events (AE). Pooled Odds Ratio (OR) were estimated using a random-effects model. RESULTS: Six RCTs with 1,229 patients were included. All studies had low risk of bias. Compared with placebo, those treated with TPO-agonists had a pooled OR of 0.12(0.08-0.17), P<0.01 for platelet transfusion avoidance, and WMD in platelet count (x10 3 /µL) of 35.6(28.6-42.7), P<0.01. Major AE did not differ between groups [Pooled OR: 0.87(0.47-1.62), P=0.66]. CONCLUSION: Compared to placebo, TPO-agonists used in cirrhotic patients with severe thrombocytopenia prior to elective invasive procedures had 88% reduced odds of requiring peri-procedural platelet transfusion and increased platelet count pre-procedure, with no difference in AE rates.

Anticoagulation and antiplatelet management in gastrointestinal endoscopy: A review of current evidence.

The role of endoscopic procedures, in both diagnostic and therapeutic purposes is continually expanding and evolving rapidly. In this context, endoscopists will encounter patients prescribed on anticoagulant and antiplatelet medications frequently. This poses an increased risk of intraprocedural and delayed gastrointestinal bleeding. Thus, there is now greater importance on optimal pre, peri and post-operative management of anticoagulant and/or antiplatelet therapy to minimise the risk of post-procedural bleeding, without increasing the risk of a thromboembolic event as a consequence of therapy interruption. Currently, there are position statements and guidelines from the major gastroenterology societies. These are available to assist endoscopists with an evidenced-based systematic approach to anticoagulant and/or antiplatelet management in endoscopic procedures, to ensure optimal patient safety. However, since the publication of these guidelines, there is emerging evidence not previously considered in the recommendations that may warrant changes to our current clinical practices. Most notably and divergent from current position statements, is a growing concern regarding the use of heparin bridging therapy during warfarin cessation and its associated risk of increased bleeding, suggestive that this practice should be avoided. In addition, there is emerging evidence that anticoagulant and/or antiplatelet therapy may be safe to be continued in cold snare polypectomy for small polyps (< 10 mm).

Oxidative stress and abdominal aortic aneurysm: potential treatment targets.

Abdominal aortic aneurysm (AAA) is a significant cause of mortality in older adults. A key mechanism implicated in AAA pathogenesis is inflammation and the associated production of reactive oxygen species (ROS) and oxidative stress. These have been suggested to promote degradation of the extracellular matrix (ECM) and vascular smooth muscle apoptosis. Experimental and human association studies suggest that ROS can be favourably modified to limit AAA formation and progression. In the present review, we discuss mechanisms potentially linking ROS to AAA pathogenesis and highlight potential treatment strategies targeting ROS. Currently, none of these strategies has been shown to be effective in clinical practice.

Emerging Therapeutic Potential of Nanoparticles in Pancreatic Cancer: A Systematic Review of Clinical Trials.

Pancreatic cancer is an aggressive disease with a five year survival rate of less than 5%, which is associated with late presentation. In recent years, research into nanomedicine and the use of nanoparticles as therapeutic agents for cancers has increased. This article describes the latest developments in the use of nanoparticles, and evaluates the risks and benefits of nanoparticles as an emerging therapy for pancreatic cancer. The Preferred Reporting Items of Systematic Reviews and Meta-Analyses checklist was used. Studies were extracted by searching the Embase, MEDLINE, SCOPUS, Web of Science, and Cochrane Library databases from inception to 18 March 2016 with no language restrictions. Clinical trials involving the use of nanoparticles as a therapeutic or prognostic option in patients with pancreatic cancer were considered. Selected studies were evaluated using the Jadad score for randomised control trials and the Therapy CA Worksheet for intervention studies. Of the 210 articles found, 10 clinical trials including one randomised control trial and nine phase I/II clinical trials met the inclusion criteria and were analysed. These studies demonstrated that nanoparticles can be used in conjunction with chemotherapeutic agents increasing their efficacy whilst reducing their toxicity. Increased efficacy of treatment with nanoparticles may improve the clinical outcomes and quality of life in patients with pancreatic cancer, although the long-term side effects are yet to be defined. The study registration number is CRD42015020009.

Barriers to the management of Diabetes Mellitus - is there a future role for Laser Doppler Flowmetry?

Diabetes Mellitus (DM) is a chronic disease that carries a significant disease burden in Australia and worldwide. The aim of this paper is to identify current barriers in the management of diabetes, ascertain whether there is a benefit from early detection and determine whether LDF has the potential to reduce the disease burden of DM by reviewing the literature relating to its current uses and development. In this literature review search terms included; laser Doppler flowmetry, diabetes mellitus, barriers to management, uses, future, applications, vasomotion, subcutaneous, cost. Databases used included Google Scholar, Scopus, Science Direct and Medline. Publications from the Australian government and textbooks were also utilised. Articles reviewed had access to the full text and were in English.