Antihypertensive drugs and risk of cancer: a systematic review and meta-analysis of randomised controlled trials

Pharmacovigilance plays an important role in monitoring adverse drug reactions (ADRs) resulting from an intervention related to medicinal products. Due to the frequencies and potentially serious consequences, ADRs pose a considerable economic and clinical burden. Patients with an underlying risk factor or established cardiovascular disease (CVD) are usually on long-term treatment, thus it is important to monitor the efficacy and safety of drugs prescribed. Modern antihypertensive drugs have been showed to effectively reduce high blood pressure (BP) hence prevents the development or complications of CVD in high-risk patients. However, there is evidence from clinical trials and observational studies suggesting the association between antihypertensive drugs and risk of cancer. Furthermore, these observations are inconsistent and the majority of clinical trials were directed towards cardiovascular outcomes. The thesis is divided into five main result chapters (4 to 8) based on the antihypertensive drug classes evaluated for risk of cancer in the systematic review and meta-analyses. Altogether, 90 randomised controlled trials (RCTs) enrolling 390,750 participants with an average follow-up of 3.5 years were included for qualitative and quantitative analysis. Angiotensin-converting enzyme inhibitor (ACEI) and risk of cancer: ACEI lowers BP through preventing the conversion of angiotensin 1 to angiotensin II by ACE in the renin-angiotensin system (RAS) pathway. In the present study, no significant association between ACEI and risk of cancer incidence or cancer-related death is reported. Factors such as tissue binding capacity, comparator used, clinical settings, age, and study duration do not affect the risk of cancer overall. Angiotensin receptor blockers (ARB) and risk of cancer: In the RAS pathway, ARB acts directly on the angiotensin type 1 (AT1) receptor to inhibit downstream signalling which results in downregulation of sympathetic activity and lowering of BP. The present meta-analysis has reported no association between ARB use and risk of cancer incidents or cancer-related mortality. Subgroup assessment indicates that valsartan has a cancer-protective effect, particularly against lung cancer. Patients’ clinical settings, age, and study duration do not influence the risk of cancer in relation to ARB overall. Calcium channel blockers (CCB) and risk of cancer: As a class, CCBs are potent vasodilators and are recommended for use as first or second-line drugs in treating hypertension. This study has reported a marginally increased risk of cancer incidents (P=0.06) but not cancer-related death overall in relation to CCB use. DHP-CCB is associated with a 9% increased risk for cancer compared to controls (P=0.05). A positive relationship is also observed with older patients and in patients with longer exposure to CCB. Therefore, a properly designed further research into the risk of a specific type of cancer with use of DHP CCB is warranted to detect a safety signal. Beta-blockers (BB) and risk of cancer: Inhibition of stress mediators from activating beta-adrenoceptors has been proposed to be the underlying mechanism by which BB lower the risk of cancer. This study has found no evidence of an association between BB and the risk of cancer or cancer-related death. Factors such as cardioselectivity, treatment indication, age and study duration do not have an impact on cancer risk altogether. Thiazide diuretics (TZ) and risk of cancer: TZ induces diuresis at the distal convoluted tubule and a great number of studies had attempted to link TZ and risk of renal cancer. No evidence of an association between TZ and the risk of cancer or cancer mortality is reported in the present study. Chemical structure differences, clinical settings, age, and study duration does not significantly influence the risk of cancer in relation to TZ use. Strengths and limitation: The strengths of the systematic review and meta-analyses conducted in this thesis include; only RCTs were included, a comprehensive search strategy spanning over 60 years with no language restrictions, and a sufficiently large sample size of over 390,000 trial participants from various clinical settings with an average 3.5 years follow-up duration. Lack of individual-level data and non-standard reporting of cancer in RCTs are the main limitations. Future recommendations: All RCT evaluating drug intervention should pre-identify cancer as one of the study outcomes as part of drug safety monitoring

Effects of aerobic exercise and dietary flavonoids on cognition: a systematic review and meta-analysis

Introduction: Studies have shown that exercise increases angiogenesis and perfusion in the hippocampus, activates neurogenesis in the dentate gyrus and increases synaptic plasticity, as well as increases the complexity and number of dendritic spines, all of which promote memory function and protect against cognitive decline. Flavonoids are gaining attention as antioxidants in health promotion due to their rich phenolic content, particularly for their modulating role in the treatment of neurodegenerative diseases. Despite this, there has been no comprehensive review of cognitive improvement supplemented with flavonoid and prescribed with exercise or a combination of the two interventions has been conducted. The purpose of this review is to determine whether a combined intervention produces better results when given together than when given separately.Methods: Relevant articles assessing the effect of physical exercise, flavonoid or in combination on cognitive related biomarkers and neurobehavioral assessments within the timeline of January 2011 until June 2023 were searched using three databases; PubMed, PROQUEST and SCOPUS.Results: A total of 705 articles were retrieved and screened, resulting in 108 studies which are in line with the objective of the current study were included in the analysis.Discussion: The selected studies have shown significant desired effect on the chosen biomarkers and neurobehavioral assessments.Systematic Review Registration: identifier: [CRD42021271001]

Vonoprazan and proton pump inhibitors in Helicobacter pylori eradication therapy: a systematic review

This systematic review sought to summarise data on the efficacy of vonoprazan, a novel potassium-competitive acid blocker, as compared with a proton pump inhibitor (PPI)-based regimen for first-line treatment of Helicobacter pylori eradication. A systematic literature search of MEDLINE, EMBASE, and the Cochrane Library using the primary keywords ‘vonoprazan’, ‘takecab’, ‘TAK-438’, ‘potassium’, ‘competitive’, ‘potassium-competitive’, ‘Helicobacter’, and ‘pylori’ was performed. Studies were included if they evaluated the eradication rate between vonoprazan-based and PPI-triple therapies. Overall, 15 studies were included in this review (three randomised controlled trials (RCTs), 12 non-RCTs). Both the included RCTs and non-RCTs showed a statistically significant superiority of vonoprazan-based therapy to PPI-based therapy as esomeprazole. Only 11 of the included studies were deemed as having good quality. In two RCTs, vonoprazan-based therapy showed a statistically significant superiority over PPI-based therapy with H. pylori eradication rates in excess of 90% (p-value < 0.001). Meanwhile, observational studies demonstrated first-line therapy eradication rates ranging between 85.0 and 95.5% in the vonoprazan-based group versus between 66.8 and 86.7% in the PPI-based group with statistical significance. In conclusion, vonoprazan-based triple therapy provided superior efficacy in H. pylori eradication versus PPI-based triple therapy. Vonoprazan shows a promising ability as a potent and long-acting, acid-reducing agent, with some potential advantages over traditional PPIs, particularly in the treatment of H. pylori infection. As a relatively new agent, whether vonoprazan is appropriate and safe for long-term or life-long use remains to be determined in the near future

The Relationship between Emotion Regulation (ER) and Problematic Smartphone Use (PSU): A Systematic Review and Meta-Analyses

Emotion Dysregulation (ED) and Problematic Smartphone Use (PSU) are two rising global issues requiring further understanding on how they are linked. This paper aims to summarize the evidence pertaining to this relationship. Five databases were systematically searched for published literature from inception until 29 March 2021 using appropriate search strategies. Each study was screened for eligibility based on the set criteria, assessed for its quality and its level of evidence was determined. The Comprehensive Meta-Analysis software program (CMA) was employed to run further analyses of the data. Twenty-one studies were included in the systematic review. Nine studies with extractable data for meta-analysis had high across-studies heterogeneity, hence subgroup analyses were performed that confirmed a significant moderate positive correlation between ED and PSU (pooled correlation coefficient, r = 0.416 (four studies, n = 1462) and r = 0.42 (three studies, n = 899), respectively) and a weak positive correlation between &ldquo;expressive suppression&rdquo; and PSU (pooled correlation coefficient, r = 0.14 (two studies, n = 608)). Meta-regression analysis showed a stronger correlation between ED and PSU (R2 = 1.0, p = 0.0006) in the younger age group. Further studies to establish and explore the mechanisms that contribute towards the positive link between ED and PSU are required to guide in the planning of targeted interventions in addressing both issues

The relationship between emotion regulation (ER) and problematic smartphone use (PSU): a systematic review and meta-analyses.

Emotion Dysregulation (ED) and Problematic Smartphone Use (PSU) are two rising global issues requiring further understanding on how they are linked. This paper aims to summarize the evidence pertaining to this relationship. Five databases were systematically searched for published literature from inception until 29 March 2021 using appropriate search strategies. Each study was screened for eligibility based on the set criteria, assessed for its quality and its level of evidence was determined. The Comprehensive Meta-Analysis software program (CMA) was employed to run further analyses of the data. Twenty-one studies were included in the systematic review. Nine studies with extractable data for meta-analysis had high across-studies heterogeneity, hence subgroup analyses were performed that confirmed a significant moderate positive correlation between ED and PSU (pooled correlation coefficient, r = 0.416 (four studies, = 1462) and r = 0.42 (three studies, = 899), respectively) and a weak positive correlation between "expressive suppression" and PSU (pooled correlation coefficient, r = 0.14 (two studies, = 608)). Meta-regression analysis showed a stronger correlation between ED and PSU (R = 1.0, = 0.0006) in the younger age group. Further studies to establish and explore the mechanisms that contribute towards the positive link between ED and PSU are required to guide in the planning of targeted interventions in addressing both issues

Virtual Reality (VR) Technology for Treatment of Mental Health Problems during COVID-19: A Systematic Review

There was a surge in psychological distress and emotional burnout during the COVID-19 pandemic. Virtual reality (VR) is helpful as a psychological intervention whilst maintaining physical or social distancing. The present systematic review assessed the role of VR as a psychological intervention tool for mental health problems during the COVID-19 pandemic. We conducted a systematic review that followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. This study used the search-related terms: (Virtual reality OR simulated-3D-environment OR VR) AND (covid! or corona!) AND (mental* OR psychologic* OR well* OR health*) AND (intervention) on six databases, i.e., MEDLINE, PsycINFO, Ovid Medline, EMBASE, ACM digital library, and Cochrane Central Register of Controlled Trials (CENTRAL) from the inception date until 23 June 2021. We finally included four studies in the systematic review out of the 379 references imported for screening. These studies reveal that VR is beneficial as a psychological tool for intervention in individuals with mental health problems. Immersed in the telepresence, interacting in a 3-D format compared to a 2-D layout, having a sense of enjoyment and engagement, activating an affective-motivational state, &ldquo;escaping&rdquo; to a virtual from the real world are pivotal faucets of VR as a psychological tool for intervention