The Protective Effect of Metformin on Abdominal Aortic Aneurysm: A Systematic Review and Meta-Analysis

BackgroundType 2 diabetes mellitus (T2DM) patients have a lower risk of abdominal aortic aneurysm (AAA) and its comorbidities, which might be associated with the usage of metformin. The objective of the study was to evaluate the role of metformin in the process of AAA development.MethodPubMed, Embase and Cochrane Library were searched up to May 15th, 2021. We implemented several methods including the risk of bias graph, GRADE system and funnel plot to assess the quality and possible bias of this study. Subgroup analysis and sensitivity analysis were applied to address quality differences and validate the robustness of the final results.ResultTen articles were enrolled after screening 151 articles searched from databases. The pooled results showed that, compared with T2DM patients without metformin, metformin prescription was associated with a slower annual growth rate of the aneurysm (mean difference (MD) -0.67 cm [95% confidence interval (CI) -1.20 ~ -0.15 cm]). Besides, metformin exposure was associated with a lower frequency of AAA events (odds ratio (OR) 0.61 [95% CI 0.41-0.92]).ConclusionMetformin alleviated both annual expansion rate and aneurysm rupture frequency in AAA patients with T2DM.Systematic Review RegistrationPROSPERO, identifier https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=217859 (CRD42020217859).

Older Age and High Α-fetoprotein Predict Higher Risk of Hepatocellular Carcinoma in Chronic Hepatitis B-Related Cirrhotic Patients Receiving Nucleos(T)ide Analogue Therapy: A Retrospective Cohort Study

Background: Nucleos(t)ide analogues (NUCs) were proved to reduce hepatocellular carcinoma (HCC) development in patients with chronic hepatitis B (CHB) infection, but data was limited on the efficacy in the CHB patients with cirrhosis. Methods: We retrospectively analyzed data from 447 patients with CHB-related cirrhosis, who initiated tenofovir/entecavir therapy during April 2007 and August 2013. They were divided into HCC (n=48) and non-HCC (n=399) groups. The mean follow-up period was 63.2 ± 34.2 months.Results: Forty-eight patients (10.7%) developed HCC during surveillance. The annual incidence rate of HCC was 2.04 (95% CI: 1.52–2.68) per 100 person-year. The cumulative incidence of HCC was 0.9%, 9.8% and 22.1% at the 1, 5 and 10 years, respectively. Significant predictors for HCC identified using multiple Cox regression analysis were age ≥50 years (hazard ratio [HR]: 2.34, 95% confidence interval [CI] = 1.08–5.1) and α-fetoprotein (AFP) ≥8 ng/ml (HR: 2.05, 95% CI = 1.1–3.84). The incidence rate of HCC was further analyzed in subgroups according to the risk factors identified by multivariate cox regression. The incidence rate of HCC was 8.67-fold higher in patients with age ≥50 years and AFP ≥8 ng/ml (3.14 per 100 person-year, 95% CI = 1.99–4.72) than those with age <50 years and AFP <8 ng/ml (0.36 per 100 person-year, 95% CI = 0.06–1.19).Conclusion: The cirrhotic CHB patients with age <50 years and AFP <8 ng/ml have the lowest annual incidence of HCC. However, the cirrhotic patients with age ≥50 years or/and AFP ≥8 ng/ml have significantly higher risk for HCC and warrant careful surveillance schedule for HCC development.

Prevalence and early-life determinants of mid-life multimorbidity: evidence from the 1970 British birth cohort

Background We sought to: [1] estimate the prevalence of multimorbidity at age 46–48 in the 1970 British Cohort Study—a nationally representative sample in mid-life; and [2] examine the association between early-life characteristics and mid-life multimorbidity. Method A prospective longitudinal birth cohort of a community-based sample from the 1970 British Cohort Study (BCS70). Participants included all surviving children born in mainland Britain in a single week in April 1970; the analytical sample included those with valid data at age 46–48 (n = 7951; 2016–2018). The main outcome was multimorbidity, which was operationalised as a binary indicator of two or more long-term health conditions where at least one of these conditions was of physical health. It also included symptom complexes (e.g., chronic pain), sensory impairments, and alcohol problems. Results Prevalence of mid-life multimorbidity was 33.8% at age 46–48. Those with fathers from unskilled social occupational class (vs professional) at birth had 43% higher risk of mid-life multimorbidity (risk ratio = 1.43, 95% confidence interval 1.15 to 1.77). After accounting for potential child and family confounding, an additional kilogram of birthweight was associated with 10% reduced risk of multimorbidity (risk ratio = 0.90, 95% confidence interval 0.84 to 0.96); a decrease of one body mass index point at age 10 was associated with 3% lower risk (risk ratio = 1.03, 95% confidence interval 1.01 to 1.05); one standard deviation higher cognitive ability score at age 10 corresponded to 4% lower risk (risk ratio = 0.96, 95% confidence interval 0.91 to 1.00); an increase of one internalising problem at age 16 was equated with 4% higher risk (risk ratio = 1.04, 95% confidence interval 1.00 to 1.08) and of one externalising problem at age 16 with 6% higher risk (risk ratio = 1.06, 1.03 to 1.09). Conclusion Prevalence of multimorbidity was high in mid-life (33.8% at age 46–48) in Britain. Potentially modifiable early-life exposures, including early-life social circumstances, cognitive, physical and emotional development, were associated with elevated risk of mid-life multimorbidity.

The Contrast Agent Pooling (C.A.P.) Sign and Imminent Cardiac Arrest: A Retrospective Study

BackgroundThe sign of contrast agent pooling (C.A.P.) in dependent part of the venous system were reported in some case reports, which happened in the patients before sudden cardiac arrest. Until now, there is no solid evidence enough to address the importance of the sign. This study aimed to assess the accuracy of the C.A.P. sign in predicting imminent cardiac arrest and the association of the C.A.P. sign with patient’s survival.MethodsThis is a retrospective cohort study. The study included 128 patients who visited the emergency department of Far Eastern Memorial Hospital, who received contrast computed tomography (CT) scan and then experienced cardiac arrest at the emergency department (from January 1, 2016 to December 31, 2018). With positive C.A.P. sign, the primary outcome is whether in-hospital cardiac arrest happens within an hour; the secondary outcome is survival to discharge.ResultsIn the study, 8.6% (N=11) patients had positive C.A.P. sign and 91.4% (N=117) patients did not. The accuracy of C.A.P. sign in predicting cardiac arrest within 1 hour is 85.94%. The C.A.P. sign had a positive association with IHCA within 1 hour after the CT scan (adjusted odds ratio 11.60, 95% confidence interval [CI] 1.97 – 68.20). The odd ration of survival to discharge is 0.0081 with positive C.A.P. sign (95% CI 0.00697 – 2.188).ConclusionThe C.A.P. sign can be considered as an alarm for imminent cardiac arrest and poor prognosis. The patients with positive C.A.P. sign were more likely to experience imminent cardiac arrest; in contrast, less likely to survive. Trial registrationThe study was approved by our institutional ethical committee (IRB No.108107-E).

Dietary patterns and internalizing symptoms in children and adolescents: A meta-analysis

Context: Studies of child and adolescent internalizing symptoms and dietary pattern have produced mixed results. Objectives: To quantify the association between dietary patterns and internalizing symptoms, including depression, in children and adolescents. Data sources: Embase, PsycINFO, MEDLINE, Web of Science and Cochrane up to March 2021. Study selection: Observational studies and randomized controlled trials with mean age ⩽ 18 years, reporting associations between diet patterns and internalizing symptoms. Data extraction: Mean effect sizes and 95% confidence intervals were determined under a random-effects model. Results: Twenty-six studies were cross-sectional, 12 were prospective, and 1 used a case-control design. The total number of participants enrolled ranged from 73,726 to 116,546. Healthy dietary patterns were negatively associated with internalizing ( r = –0.07, p < 0.001, 95% confidence interval [–0.12, 0.06]) and depressive symptoms ( r = –0.10, p < 0.001, 95% confidence interval [–0.18, –0.08]). Effect sizes were larger for studies of healthy dietary patterns and internalizing and depressive symptoms using self-report versus parent-report measures, as well as in cross-sectional studies of healthy dietary patterns and depression compared to prospective studies. Unhealthy dietary patterns were positively associated with internalizing ( r = 0.09, p < 0.001, 95% confidence interval [0.06, 0.14]) and depressive symptoms ( r = 0.10, p < 0.01, 95% CI [0.05, 0.17]). Larger effect sizes were observed for studies of unhealthy dietary patterns and internalizing and depressive symptoms using self-report versus parent-report measures. Limitations: A lack of studies including clinical samples and/or physician diagnosis, and a paucity of studies in which anxiety symptoms were the primary mental health outcome. Conclusion: Greater depression and internalizing symptoms are associated with greater unhealthy dietary patterns and with lower healthy dietary intake among children and adolescents.

Nephrologist Interventions to Avoid Kidney Replacement Therapy in Acute Kidney Injury

<b><i>Background:</i></b> Based on the pathophysiology of acute kidney injury (AKI), it is plausible that certain early interventions by the nephrologist could influence its trajectory. In this study, we investigated the impact of 5 early nephrology interventions on starting kidney replacement therapy (KRT), AKI progression, and death. <b><i>Methods:</i></b> In a prospective cohort at the Hospital Civil of Guadalajara, we followed up for 10 days AKI patients in whom a nephrology consultation was requested. We analyzed 5 early interventions of the nephrology team (fluid adjustment, nephrotoxic withdrawal, antibiotic dose adjustment, nutritional adjustment, and removal of hyperchloremic solutions) after the propensity score and multivariate analysis for the risk of starting KRT (primary objective), AKI progression to stage 3, and death (secondary objectives). <b><i>Results:</i></b> From 2017 to 2020, we analyzed 288 AKI patients. The mean age was 55.3 years, 60.7% were male, AKI KDIGO stage 3 was present in 50.5% of them, sepsis was the main etiology 50.3%, and 72 (25%) patients started KRT. The overall survival was 84.4%. Fluid adjustment was the only intervention associated with a decreased risk for starting KRT (odds ratio [OR]: 0.58, 95% confidence interval [CI]: 0.48–0.70, and <i>p</i> ≤ 0.001) and AKI progression to stage 3 (OR: 0.59, 95% CI: 0.49–0.71, and <i>p</i> ≤ 0.001). Receiving vasopressors and KRT were associated with mortality. None of the interventions studied was associated with reducing the risk of death. <b><i>Conclusions:</i></b> In this prospective cohort study of AKI patients, we found for the first time that early nephrologist intervention and fluid prescription adjustment were associated with lower risk of starting KRT and progression to AKI stage 3.

Magma reservoir beneath Azumayama Volcano, NE Japan, as inferred from a three-dimensional electrical resistivity model explored by means of magnetotelluric method

An electrical resistivity model beneath Azumayama Volcano, NE Japan, is explored using magnetotelluric method to probe the magma/hydrothermal fluid distribution. Azumayama is one of the most concerning active volcanoes capable of producing a potential eruption triggered by the 2011 Tohoku-Oki Earthquake. The three-dimensional resistivity model reveals a conductive magma reservoir (< 3 Ωm) at depths of 3–15 km below sea level (bsl). The 67% and 90% confidence intervals of resistivity are 0.2–5 Ωm and 0.02–70 Ωm, respectively, for the magma reservoir. We assumed dacitic melt + rock at a shallow depth of 4 km bsl and andesitic melt + rock at a greater depth of 9 km bsl. The confidence interval of resistivity cannot be explained by using dacitic melt + rock condition at a depth of 4 km bsl. This suggests that very conductive hydrothermal fluids coexist with dacitic melt and rock in the shallow part of the magma reservoir. For the depth of 9 km bsl, the 67% confidence interval of resistivity is interpreted as water-saturated (8.0 weight %) andesitic melt–mafic rock complex with melt volume fractions greater than 4 volume %, while the shear wave velocity requires the fluid and/or melt volume fraction of 6–7 volume % at that depth. Considering the fluid and/or melt volume fraction of 6–7 volume %, the conductive hydrous phase is likewise required to explain the wide range of the 67% confidence interval of resistivity. The Mogi inflation source determined from geodetic data lies on the resistive side near the top boundary of the conductive magma reservoir at a depth of 2.7 or 3.7 km bsl. Assuming that the resistivity of the inflation source region is above the upper bound of the confidence interval of resistivity for the conductive magma reservoir and that the source region is composed of hydrothermal fluid + rock, the resistivity of the source region is explained by a hydrothermal fluid volume fraction below 5 volume %, which is the percolation threshold porosity in an effusive eruption. This indicates that the percolation threshold characterizes the inflation source region.

The Non-linear Relationship Between Normal Range Systolic Blood Pressure and Cardiovascular or All-Cause Mortality Among Elderly Population

Purpose: The aim was to explore the association of normal range SBP with cardiovascular and all-cause mortality in older adults without hypertension.Methods: Participants aged ≥ 65 years without hypertension and those had an SBP level between 90 and 129 mmHg were included from the National Health and Nutrition Examination Survey (1999–2014). SBP was categorized into: 90–99, 100–109, 110–119, and 120–129 mmHg. Multivariate Cox regression was performed with hazard ratio (HR) and 95% confidence interval (CI).Results: Of the 1,074 participants, 584 were men (54.38%). Compared with participants with SBP level ranged 110 to 119 mmHg, the HRs for all-cause mortality risk was 1.83 (95% CI: 1.04, 3.23) for SBP level ranged 90 to 99 mm Hg, 0.87 (95% CI: 0.54, 1.41) for SBP level ranged 100 to 109 mmHg, and 1.30 (95% CI: 0.96, 1.75) for SBP level ranged 120 to 129 mmHg (P for trend = 0.448), and the HR for cardiovascular mortality risk was 3.30 (95% CI: 0.87, 12.54) for SBP level ranged 90 to 99 mmHg, 0.35(95% CI: 0.08, 1.56) for SBP level ranged 100 to 109 mmHg, and 1.75 (95% CI: 0.78, 3.94) for SBP level ranged 120 to 129 mm Hg (P for trend = 0.349) after confounders were adjusted.Conclusion: These were a nonlinear association of normal range SBP level with all-cause and cardiovascular death in older adults.

Vaccines against Covid-19, venous thromboembolism, and thrombocytopenia. A population-based retrospective cohort study

Background Covid-19 vaccines may increase the risk of venous thromboembolism (VTE), thrombocytopenia (TCP), and VTE associated with TCP. We aimed at estimating this risk by age and sex, after the first dose of both adenovirus vector-based and mRNA-based Covid-19 vaccines, and after the second dose of m-RNA vaccines. Methods In this population-based retrospective cohort study, we examined three groups: 1 662 719 people 10 years of age and over vaccinated with the first dose of a Covid-19 vaccine, 622 778 with the second dose, and 190 616 diagnosed of Covid-19 in the same period (between1 January 2021 and 18 April 2021). The rates of various clinical presentations of VTE and TCP were compared with those in the reference population (7 013 040 people served by the health care system in 2919). The two primary outcomes were the observed 21 day rate of a composite variable of cerebral venous sinus thrombosis, mesenteric thrombosis, portal vein thrombosis, or any venous thromboembolism (VTE) associated with thrombocytopenia (TCP), and the rate of any VTE associated with TCP (VTE+TCP). Analyses were standardised by age and sex. Findings The 21 day rate per 100 000 of the primary composite variable was 2.15 in the reference population, 5.65 following the first vaccine dose (standardised difference, 2.53 (95 percent confidence interval, 1.04-4.00), and 7.23 following the second dose (standardised difference, 4.07 (95 percent confidence interval, 1.43-6.70). The event rates of VTE+TCP and of all the secondary variables showed the same patterns. Excess event rates were higher in men than in women, and they were not especially increased in any particular age group. All Covid-19 vaccines were associated with increased rates of the outcome variables. Excess event rates were many-fold higher in the Covid-19 cohort. Interpretation We observed small increases of rates of venous thromboembolism in usual and unusual anatomical sites and of thrombocytopenia in recipients of both adenovirus vector and mRNA vaccines against Covid-19. Excess rates were higher in men than in women and they were not particularly elevated in any specific age group.

Anopheles bionomics in a malaria endemic area of southern Thailand

Background Ivermectin mass drug administration (MDA) could accelerate malaria elimination in the Greater Mekong Subregion. This study was performed to characterize the bionomics of Anopheles in Surat Thani province, Thailand. Methods Mosquitoes were collected via human landing collections between February and October 2019. Anopheles mosquitoes were morphologically identified to species. Primary Anopheles malaria vectors were dissected to assess parity status, and a subset were evaluated for molecular identification and Plasmodium detection. Results A total of 17,348 mosquitoes were collected during the study period; of these, 5777 were Anopheles mosquitoes. Morphological studies identified 15 Anopheles species, of which the most abundant were Anopheles minimus (s.l.) (87.16%, n = 5035), An. dirus s.l. (7.05%, n = 407) and An. barbirostris s.l. (2.86%, n = 165). Molecular identification confirmed that of the An. minimus s.l. mosquitoes collected, 99.80% were An. minimus (s.s.) (n = 484) and 0.2% were An. aconitus (n = 1), of the An. dirus (s.l.) collected, 100% were An. baimaii (n = 348), and of the An. maculatus (s.l.) collected, 93.62% were An. maculatus (s.s.) (n = 44) and 6.38% were An. sawadwongporni (n = 3). No Anopheles mosquito tested was Plasmodium positive (0/879). An average of 11.46 Anopheles were captured per collector per night. There were differences between species in hour of collection (Kruskal–Wallis H-test: χ2 = 80.89, P < 0.0001, n = 5666), with more An. barbirostris (s.l.) and An. maculatus (s.l.) caught earlier compared to An. minimus (s.l.) (P = 0.0001 and P < 0.0001, respectively) and An. dirus (s.l.) (P = 0.0082 and P < 0.001, respectively). The proportion of parous An. minimus (s.l.) captured by hour increased throughout the night (Wald Chi-square: χ2 = 17.31, P = 0.000, odds ratio = 1.0535, 95% confidence interval 1.0279–1.0796, n = 3400). Overall, An. minimus (s.l.) parity was 67.68% (2375/3509) with an intra-cluster correlation of 0.0378. A power calculation determined that an An. minimus (s.l.) parity reduction treatment effect size = 34%, with four clusters per treatment arm and a minimum of 300 mosquitoes dissected per cluster, at an α = 0.05, will provide 82% power to detect a significant difference following ivermectin MDA. Conclusions The study area in Surat Thani province is an ideal location to evaluate the impact of ivermectin MDA on An. minimus parity. Graphical abstract