Renal effects of NO-inhibition in patients with cirrhosis vs. healthy controls: a randomized placebo-controlled crossover study.

BACKGROUND: Nitric oxide (NO) is an important regulator of renal hemodynamics and sodium excretion. Systemic and splanchnic NO-synthesis is increased in liver cirrhosis contributing to the characteristic hyperdynamic circulation. The significance of renal NO in human cirrhosis is not clear. AIMS: In order to clarify the role of NO in the regulation of renal hemodynamics and sodium excretion in human cirrhosis, we studied the effects of N(G)-monomethyl-L-arginine (L-NMMA) - a nonselective NO-inhibitor - on blood pressure (MAP), heart rate (HR), GFR, RPF, UNa × V, FENa, FELi and plasma levels of renin, angII, aldo, ANP, BNP and cGMP in 13 patients with cirrhosis (Child gr.A: 8; Child gr.B+C: 5) and 13 healthy controls. METHODS: The study was randomized and placebo-controlled. Renal hemodynamics were assessed by measuring renal clearance of (51) Cr-EDTA and (125) I-Hippuran for GFR and RPF, respectively. RESULTS: L-NMMA induced a similar, significant increase in MAP in both groups and a more pronounced relative decrease in HR in the CIR group (P = 0.0209, anova). L-NMMA did not change GFR in any group, but RPF decreased significantly in both groups, but most pronouncedly in CIR (P = 0.0478, anova). FENa decreased significantly in both groups after l-NMMA, but the response was again most pronounced in the CIR group (P = 0.0270, anova). All parameters remained stable after placebo. No significant differences were observed between the effects of L-NMMA in Child gr.A vs. Child gr. B+C patients. CONCLUSION: The data supports the hypothesis that renal NO is enhanced in human cirrhosis.

COVID-19 vaccination coverage for half a million non-EU migrants and refugees in England.

Despite evidence suggesting that some migrants are at risk of under-immunization and have experienced severe health inequities during the pandemic, data are limited on migrants' COVID-19 vaccine coverage globally. Here we linked data from non-European Union migrants and resettled refugees to the national COVID-19 vaccination dataset in England. We estimated patterns in second and third dose delays and overdue doses between 12 December 2020 and 20 April 2022 by age, visa type and ethnicity. Of the 465,470 linked records, 91.8% (427,073/465,470) of migrants received a second dose and 51.3% (238,721/465,470) received a third. Refugees had the highest risk of delayed second (adjusted odds ratio 1.66; 95% confidence interval 1.55-1.79) and third dose (1.55; 1.43-1.69). Black migrants were twice as likely to have a second dose delayed (2.37; 2.23-2.54) than white migrants, but this trend reversed for the third dose. Older migrants (>65 years) were four times less likely to have received their second or third dose compared with the general population in England aged >65 or older. Policymakers, researchers and practitioners should work to understand and address personal and structural barriers to vaccination for diverse migrant populations.

Daily use of lateral flow devices by contacts of confirmed COVID-19 cases to enable exemption from isolation compared with standard self-isolation to reduce onward transmission of SARS-CoV-2 in England: a randomised, controlled, non-inferiority trial.

BACKGROUND: In the UK, during the study period (April to July, 2021), all contacts of people with COVID-19 were required to self-isolate for 10 days, which had adverse impacts on individuals and society. Avoiding the need to self-isolate for those who remain uninfected would be beneficial. We investigated whether daily use of lateral flow devices (LFDs) to test for SARS-CoV-2, with removal of self-isolation for 24 h if negative, could be a safe alternative to self-isolation as a means to minimise onward transmission of the virus. METHODS: We conducted a randomised, controlled, non-inferiority trial in adult contacts identified by COVID-19 contact tracing in England. Consenting participants were randomly assigned to self-isolation (single PCR test, 10-day isolation) or daily contact testing (DCT; seven LFD tests, two PCR tests, no isolation if negative on LFD); participants from a single household were assigned to the same group. Participants were prospectively followed up, with the effect of each intervention on onward transmission established from routinely collected NHS Test and Trace contact tracing data for participants who tested PCR-positive for SARS-CoV-2 during the study period and tertiary cases arising from their contacts (ie, secondary contacts). The primary outcome of the study was the attack rate, the percentage of secondary contacts (close contacts of SARS-CoV-2-positive study participants) who became COVID-19 cases (tertiary cases) in each group. Attack rates were derived from Bernoulli regression models using Huber-White (robust) sandwich estimator clustered standard errors. Attack rates were adjusted for household exposure, vaccination status, and ability to work from home. The non-inferiority margin was 1·9%. The primary analysis was a modified intention-to-treat analysis excluding those who actively withdrew from the study as data from these participants were no longer held. This study is registered with the Research Registry (number 6809). Data collection is complete; analysis is ongoing. FINDINGS: Between April 29 and July 28, 2021, 54 923 eligible individuals were enrolled in the study, with final group allocations (following withdrawals) of 26 123 (52·6%) participants in the DCT group and 23 500 (47·4%) in the self-isolation group. Overall, 4694 participants tested positive for SARS-CoV-2 by PCR (secondary cases), 2364 (10·1%) in the self-isolation group and 2330 (8·9%) in the DCT group. Adjusted attack rates (among secondary contacts) were 7·5% in the self-isolation group and 6·3% in the DCT group (difference of -1·2% [95% CI -2·3 to -0·2]; significantly lower than the non-inferiority margin of 1·9%). INTERPRETATION: DCT with 24 h exemption from self-isolation for essential activities appears to be non-inferior to self-isolation. This study, which provided evidence for the UK Government's daily lateral flow testing policy for vaccinated contacts of COVID-19 cases, indicated that daily testing with LFDs could allow individuals to reduce the risk of onward transmission while minimising the adverse effects of self-isolation. Although contacts in England are no longer required to isolate, the findings will be relevant for future policy decisions around COVID-19 or other communicable infections. FUNDING: UK Government Department of Health and Social Care.

Is agricultural engagement associated with lower incidence or prevalence of cardiovascular diseases and cardiovascular disease risk factors? A systematic review of observational studies from low- and middle-income countries.

Non-communicable diseases, such as cardiovascular diseases (CVDs), diabetes and cancer account for more than half of the global disease burden, and 75% of related deaths occur in low- and middle-income countries (LMICs). Despite large regional variations in CVD incidence and prevalence, CVDs remain the leading causes of death worldwide. With urbanisation, developing nations are undergoing unprecedented labour-force transitions out of agriculture and into types of non-agricultural employment, mainly in the industry and service sectors. There are few studies on the effect of these transitions on CVDs and CVD risk factors in LMICs. We systematically searched MEDLINE, PubMed, EMBASE and the Cochrane Library from January 1950 to January 2017 to assess the association of engaging in agriculture compared to types of non-agricultural employment (e.g. services and manufacturing) with CVD incidence, prevalence and risk factors. Studies were included if they: included participants who engaged in agriculture and participants who did not engage in agriculture; measured atherosclerotic CVDs or their modifiable risk factors; and involved adults from LMICs. We assessed the quality of evidence in seven domains of each study. Prevalence ratios with 95% confidence intervals were calculated and compared in forest plots across studies. Study heterogeneity did not permit formal meta-analyses with pooled results. There was a lack of publications on the primary outcomes, atherosclerotic CVDs (n = 2). Limited evidence of varying consistency from 13 studies in five countries reported that compared with non-agricultural workers, mainly living in urban areas, rural agriculture workers had a lower prevalence of hypertension, overweight and obesity; and a higher prevalence of underweight and smoking. High quality evidence is lacking on the associations of engaging in and transitioning out of agriculture with atherosclerotic CVDs and their modifiable risk factors in LMICs. There is a need for interdisciplinary longitudinal studies to understand associations of types of employment and labour-force transitions with CVD burdens in LMICs.

Relationship between mercury in blood and 24-h ambulatory blood pressure in Greenlanders and Danes.

BACKGROUND: Intake of mercury with food items from sea mammals and fish has been suggested to be involved in cardiovascular disease, but the relationship between mercury in blood and 24-h ambulatory blood pressure (BP) has never been studied. METHODS: We measured mercury in blood and 24-h BP in four groups of healthy subjects: group 1, Danes living in Denmark consuming European food; group 2, Greenlanders living in Denmark consuming European food; group 3, Greenlanders living in Greenland consuming European food; and group 4, Greenlanders living in Greenland consuming mainly traditional Greenlandic food. RESULTS: Mercury in blood was highest in Greenlanders and increased when they lived in Greenland and consumed traditional Greenlandic food (group 1: 2.2 microg/L (median), group 2: 4.8 microg/L, group 3: 10.8 microg/L, and group 4: 24.9 microg/L). The 24-h BP was the same in all three groups of Greenlanders. However, 24-h diastolic BP was lower among Greenlanders than Danes (71 v 76 mm Hg, P < .000) and 24-h pulse pressure was higher (54 v 50 mm Hg, P < .000). Mercury in blood was significantly and positively correlated to pulse pressure (rho = 0.272, P < .01). CONCLUSIONS: Pulse pressure was higher and diastolic BP was lower in Greenlanders than Danes. Pulse pressure increased with higher mercury content in the blood. Although genetic factors must be responsible to some extent for the difference in pulse pressure between Greenlanders and Danes, the present results seem to support the hypothesis that mercury intake from maritime food is involved in cardiovascular disease.

Plasma amino acids in Greenlanders and Danes: influence of seasons, residence, ethnicity, and diet.

Basal metabolic rate is elevated among circumpolar populations. It has been our hypotheses that this is reflected in the levels of plasma amino acids, that amino acid concentration in plasma differs between Greenlanders and Danes, and that this difference is related to residence, ethnicity, diet, and season. The purpose of the study was to measure plasma amino acids in Greenlanders and Danes and to analyze the influence of residence, ethnicity, diet, and season. Amino acids in plasma were measured in four groups of healthy subjects both during summer and winter: Group 1, Danes living in Denmark consuming European food; Group 2, Greenlanders living in Denmark consuming European food; Group 3, Greenlanders living in Greenland consuming European food; and Group 4, Greenlanders living in Greenland consuming mainly traditional Greenlandic food. Amino acids were determined by pre-column derivatization with o-phthaldialdehyde and reverse-phase high-performance liquid chromatography with gradient elution and fluorescence detection. Most plasma amino acids were lower during summer than winter in Greenlanders living in Greenland. Comparison of the four groups showed that residence in Greenland was the most important influencing factor for the concentration of plasma amino acids, whereas ethnicity and diet had only a very modest or no effect. These findings could not be attributed to changes in thyroid function. However, the level of physical activity was significantly higher in Groups 3 and 4 than in Groups 1 and 2. Because exercise reduces the amino acid pool in plasma, it is possibly that the higher physical activity among Greenlanders living in Greenland explains the reduction in plasma amino acids during summer. It is concluded that plasma amino acids were lower during summer than winter in Greenlanders living in Greenland compared with Greenlanders in Denmark and Danes. This difference might be due to the higher level of physical activity among Greenlanders in Greenland during the summer period.

Ethnic, geographic and dietary influences upon vasoactive hormones and blood pressure among Greenland Inuit and Danes.

AIM: To study levels of vasoactive hormones and urinary excretion of sodium and potassium between groups of Greenland Inuit and Danes, and to analyse the relationship between these hormones and 24-h blood pressure, including nightly blood pressure dips and pulse pressure. METHODS: 145 Greenlandic participants were categorized in three groups according to degree of westernization, based on dietary habits and current place of residence; 41 Danes were included as controls. Twenty-four-hour blood pressure was measured. Venous plasma concentrations of vasoactive hormones were measured. Urine was collected for 24 hours for analysis of excretion of sodium and potassium. RESULTS: The Inuit population of Greenland had a lower diastolic blood pressure, a higher pulse pressure and lower nocturnal blood pressure dip than Danes had. Angiotensin II in plasma and urine excretion of potassium were higher among Greenlanders compared with Danes, irrespective of diet and place of residence. Aldosterone and urine excretion of sodium were significantly higher among participants in Denmark compared with participants in Greenland. Brain natriuretic peptide and atrial natriuretic peptide were independently and negatively associated with diastolic blood pressure, and vasopressin was positively associated with systolic blood pressure and pulse pressure. Ethnic differences in the effect of vasoactive hormones or urinary sodium and potassium excretion could not explain the difference in blood pressure. CONCLUSION: It is suggested that a high dietary intake of potassium and low sodium intake among Greenlanders may affect blood pressure. Further attention should be drawn to the occurrence of high pulse pressure and high activity in the renin-angiotensin system in Inuit populations.