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1.
ESC Heart Fail ; 8(2): 1717-1721, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-34596976

RESUMO

AIMS: Concern has been raised that treatment with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may increase the expression of angiotensin-converting enzyme 2 (ACE2), which acts as the entry receptor for SARS-CoV-2, and lead to an increased risk of death from SARS-CoV-2. We aimed to address this concern by evaluating the in vivo relationship of treatment with ACE inhibitors and angiotensin receptor blockers (ARB) with circulating plasma concentrations of ACE2 in a large cohort of patients with established cardiovascular disease (n = 1864) or cardiovascular risk factors (n = 2144) but without a history of heart failure. METHODS AND RESULTS: Angiotensin-converting enzyme 2 was measured in 4008 patients (median age 68, 33% women, 31% on ACE-inhibitors, 31% on ARB) using the SOMAscan proteomic platform (SomaLogic Inc, Colorado, USA). Plasma concentration of ACE2 was comparable in 1250 patients on ACE inhibitors (mean 5.99) versus patients without ACE inhibitors (mean 5.98, P = 0.54). Similarly, plasma concentration of ACE2 was comparable in 1260 patients on ARB (mean 5.99) versus patients without ARB (mean 5.98, P = 0.50). Plasma concentration of ACE2 was comparable in 2474 patients on either ACE inhibitors or ARB (mean 5.99) versus patients without ACE inhibitors or ARB (mean 5.98, P = 0.31). Multivariable quantile regression model analysis confirmed the lack of association between treatment with ACE inhibitors or ARB and ACE2 concentrations. Body mass index showed the only positive association with ACE2 plasma concentration (effect 0.015, 95% confidence interval 0.002 to 0.028, P = 0.024). CONCLUSIONS: In a large cohort of patients with established cardiovascular disease or cardiovascular risk factors but without heart failure, ACE inhibitors and ARB were not associated with higher plasma concentrations of ACE2.


Assuntos
Enzima de Conversão de Angiotensina 2 , COVID-19 , Idoso , Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina , Feminino , Humanos , Masculino , Proteômica , Sistema Renina-Angiotensina , SARS-CoV-2
2.
J Environ Manage ; 300: 113827, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34649320

RESUMO

This study developed and evaluated a high-purity butyrate producing bioprocess from food waste by combining dry fermentation (DF) with a microbial fuel cell (MFC). Acclimatization of a DF reactor with an enrichment culture resulted in high food waste degradation (VS removed, %) and butyrate production. A high VS degradation of 81%, butyrate concentration of up to 24 gCODbutyrate/L and butyrate yields of 497 gCODbutyrate/kg VSadded was obtained in the DF reactor. As a result, butyrate comprised 83% of all short chain fatty acids (SCFA) in the DF broth. Acetate (10%) and propionate (7%) comprised the rest of the SCFA. The butyrate composition was further purified by feeding the DF broth to a multi-electrode MFC enriched with anode respiring bacteria (ARB) such as Geobacter sp. (>55%). The ARB in the MFC removed acetate and propionate while purified butyrate was recovered in the MFC effluent. Butyrate purity in the MFC effluent reached as high as 99% at hydraulic retention time of 72 h. Along with butyrate purification, the MFC produced electric power in a range of 0.1-0.6 Wh/gCODbutyraterecovered (or 0.01-7.85 kWh/ton of food waste), demonstrating that MFCs can be an energy-positive butyrate purification bioprocess.


Assuntos
Fontes de Energia Bioelétrica , Eliminação de Resíduos , Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina , Butiratos , Eletricidade , Eletrodos , Fermentação , Alimentos
4.
Ann Palliat Med ; 10(9): 9963-9973, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34628920

RESUMO

BACKGROUND: Few studies have focused on the clinical features of hypertrophic cardiomyopathy (HCM) with enlarged left ventricle (ELV). METHODS: In this study, participants were patients with HCM (n=170), who were divided into two groups [ELV and normal left ventricle (NLV)] according to left ventricle size. Age at diagnosis, sex, complications, electrocardiogram (ECG), symptoms, drug treatment, and echocardiographic parameters were compared between the NLV (n=153) and ELV (n=17) groups. RESULTS: The incidence of end-stage HCM (ES-HCM) among all HCM patients was 5.29%, while that of ELV was 10.0%. For all patients with HCM and those with asymmetric septal HCM (ASHCM), there were more males with ELV than NLV. Of the patients with HCM and ASHCM, left ventricular ejection fraction (LVEF) was significantly lower in the ELV group than the NLV group; accordingly, the rates of diuretics use in the ELV group were higher than those in the NLV group. Among apical HCM (ApHCM) patients, the left atrial diameter (LAd), incidence of atrial fibrillation (Af) or ST-T change, and rate of angiotensin converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) use were all higher in the ELV group compared to the NLV group. CONCLUSIONS: These findings suggest that the prevalence of ES-HCM in HCM patients with ELV was higher than those with NLV. Additionally, ELV is more common in men than women and there are differences in the clinical features of different types of HCM with ELV.


Assuntos
Antagonistas de Receptores de Angiotensina , Cardiomiopatia Hipertrófica , Inibidores da Enzima Conversora de Angiotensina , Feminino , Humanos , Masculino , Volume Sistólico , Função Ventricular Esquerda
6.
Ann Saudi Med ; 41(5): 268-273, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34618609

RESUMO

BACKGROUND: The angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARBs) are widely used for the treatment of hypertension (HT). Whether the use of these drugs increases the infectivity of novel coronavirus and results in an additional risk for morbidity and mortality of COVID-19 is a matter of interest. OBJECTIVES: Assess the effect of ACEI/ARBs compared with other hypertensives on the clinical course and outcome in COVID-19 pneumonia. DESIGN: Retrospective. SETTINGS: Tertiary care hospital. PATIENTS AND METHODS: We collected data on adult inpatients with COVID-19 pneumonia using ACEI/ARBs versus other antihypertensives between 15 March 2020, and 15 February 2021. MAIN OUTCOME MEASURES: Severity, clinical course, mortality, and time to PCR negativity between patients using ACEI/ARBs and other antihypertensives. SAMPLE SIZE: 435 RESULTS: ACEI/ARBs were used by 203 patients (46.6%) (median age: 71 [41-94] years), while 232 patients (53.4%) were using other antihypertensives (median age: 69 [22-93] years, P=.645 vs age of ACEI/ARB users). There were no statistically significant differences between the ACEI/ARBs users and non-users in the number of patients admitted to intensive care (65 cases [32%] vs. 74 cases [31.9%], P=.978), the median duration of stay in hospital (8 [1-54] days vs.7 [1-55] days, P=.806) the median duration of ICU stay (8 [1-40] days vs. 6 [1-25] days), and the mortality rate (48 cases [23.6%] vs. 61 [26.3%], P=.525). While the median days before transfer to the ICU was shorter in ACE/ARBI non-users (2 [1-15] days vs. 3 [1-21] days, P=.02), the difference was not important clinically. The median time to PCR negativity was similar in ACEI/ARBs users and non-users (13 [7-34] days for users and 13 [5-45] days for non-users), (P=.083). CONCLUSIONS: ACEI/ARB use is probably unrelated to poor prognosis in COVID-19 pneumonia inpatients. ACEI/ARBs did not prolong the time to PCR negativity. We conclude that using ACEI/ARBs probably does not increase the infectivity of SARS-CoV-2. LIMITATIONS: Pharmacological therapies were not discussed in detail. The use of corticosteroids may affect the time to PCR negativity. We could not analyze the effect of obesity because of a lack of data. CONFLICT OF INTEREST: None.


Assuntos
COVID-19 , Hipertensão , Adulto , Idoso , Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina , Anti-Hipertensivos , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Estudos Retrospectivos , SARS-CoV-2
7.
Clin Drug Investig ; 41(10): 907-915, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34533783

RESUMO

BACKGROUND: Sacubitril-valsartan is effective in reducing the N-terminal pro-B-type natriuretic peptide level of hospitalized patients with acute decompensated heart failure, with a high acquisition cost compared with enalapril treatment. OBJECTIVE: This study aimed to determine the cost utility of sacubitril-valsartan compared with enalapril for acute decompensated heart failure treatment. METHODS: A Markov model was constructed to project the total costs, life-years, quality-adjusted life-years (QALYs) of early initiation, and a 2-month delay of sacubitril-valsartan treatment and enalapril treatment in hospitalized patients with acute decompensated heart failure over a lifetime horizon from a Thai healthcare system perspective. Clinical inputs were mainly derived from the PIONEER-HF and PARADIGM-HF trials, together with Thai epidemiological data. Cost data were based on the Thai population. All costs and outcomes were discounted at 3% annually. A series of sensitivity analyses were performed. RESULTS: Compared with enalapril, sacubitril-valsartan incurred a higher total cost per year (THB 42,994 [US$1367.48] vs THB 19,787 [US$629.37]), and it gained more QALYs (4.969 vs 4.755). The incremental cost-effectiveness ratio was THB 108,508/QALY (US$3451.26/QALY). Early initiation of sacubitril-valsartan treatment was more cost effective than delayed treatment. Sensitivity analyses revealed that at a level of willingness to pay of THB 160,000/QALY (US$5089/QALY), sacubitril-valsartan was a cost-effective strategy of about 60%. CONCLUSIONS: Sacubitril-valsartan is cost effective in patients with acute decompensated heart failure. However, the results are highly dependent on the long-term cardiovascular mortality, and they are applicable only to Thailand or countries with a similarly structured healthcare system. Long-term registries should be pursued to decrease the uncertainty around long-term mortality.


Assuntos
Enalapril , Insuficiência Cardíaca , Aminobutiratos/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Compostos de Bifenilo , Análise Custo-Benefício , Combinação de Medicamentos , Enalapril/uso terapêutico , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Hospitalização , Humanos , Volume Sistólico , Tetrazóis/uso terapêutico , Tailândia , Valsartana
8.
Intern Med ; 60(17): 2807-2809, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34470986

RESUMO

Sacubitril/valsartan has demonstrated its prognostic advantageousness over enalapril in patients with heart failure with a reduced ejection fraction. However, the optimal therapeutic strategy using sacubitril/valsartan in real-world practice, particularly among a Japanee cohort, remains uncertain. A 75-year-old man with systolic heart failure and chronic kidney disease was administered sacubitril/valsartan. Plasma B-type natriuretic peptide transiently increased, accompanied by an increase in the urine volume, which allowed us to terminate loop diuretics. The estimated glomerular filtration rate as well as heart failure symptom improved at the one-month follow-up. Sacubitril/valsartan might be a promising option to preserve the renal function and improve clinical outcomes when the dose of concomitant diuretics can be decreased, although further large-scale studies are warranted to validate our hypothesis.


Assuntos
Insuficiência Cardíaca Sistólica , Insuficiência Cardíaca , Insuficiência Renal Crônica , Idoso , Aminobutiratos/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Compostos de Bifenilo , Combinação de Medicamentos , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca Sistólica/tratamento farmacológico , Humanos , Japão , Masculino , Neprilisina , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Volume Sistólico , Tetrazóis/uso terapêutico , Resultado do Tratamento , Valsartana/uso terapêutico
9.
Water Res ; 204: 117630, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34536683

RESUMO

Antibiotic resistant bacteria (ARB) and resistance genes (ARGs) are emerging environmental pollutants with strong pathogenicity. In this study, surface plasma was developed to inactivate the donor ARB with Escherichia coli (AR E. coli) as a model, eliminate ARGs, and inhibit conjugative transfer of ARGs in water, highlighting the influences of concomitant inorganic ions. Surface plasma oxidation significantly inactivated AR E. coli, eliminated ARGs, and inhibited conjugative transfer of ARGs, and the presence of NO3-, Cu2+, and Fe2+ all promoted these processes, and SO42- did not have distinct effect. Approximately 4.5log AR E. coli was inactivated within 10 min treatment, and it increased to 7.4log AR E. coli after adding Fe2+. Integrons intI1 decreased by 3.10log (without Fe2+) and 4.43log (adding Fe2+); the addition of Fe2+ in the surface plasma induced 99.8% decline in the conjugative transfer frequency. The inhibition effects on the conjugative transfer of ARGs were mainly attributed to the reduced reactive oxygen species levels, decreased DNA damage-induced response, decreased intercellular contact, and down-regulated expression of plasmid transfer genes. This study disclosed underlying mechanisms for inhibiting ARGs transfer, and supplied a prospective technique for ARGs control.


Assuntos
Escherichia coli , Genes Bacterianos , Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina , Antibacterianos/farmacologia , Bactérias/genética , Resistência Microbiana a Medicamentos , Escherichia coli/genética , Estudos Prospectivos , Águas Residuárias
10.
G Ital Cardiol (Rome) ; 22(10): 854-860, 2021 Oct.
Artigo em Italiano | MEDLINE | ID: mdl-34570120

RESUMO

Sacubitril/valsartan (S/V) has been shown to reduce the risk of cardiovascular death or heart failure hospitalization and improve symptoms in chronic heart failure with reduced ejection fraction compared to enalapril. After 7 years since the publication of the results of PARADIGM-HF, further insight has been gained with potential new indications. Two prospective randomized multicenter studies (PIONEER-HF and TRANSITION) in patients hospitalized for acute heart failure (AHF) have shown an improved clinical outcome and biomarker profile as compared to enalapril, and good tolerability, safety and feasibility of initiating in-hospital administration of S/V. Furthermore, some studies have highlighted the favorable effects of S/V in attenuating adverse myocardial remodeling, supporting an early benefit after treatment. Observational data from non-randomized studies in AHF report that in-hospital and pre-discharge prescription of evidence-based drugs associated with better survival still remains suboptimal. Additionally, the COVID-19 pandemic has also negatively impacted on outpatient activities. Therefore, hospitalization, a real crossroads in the history of heart failure, must become a management and therapeutic opportunity for our patients. The objective of this ANMCO position paper is to encourage and facilitate early S/V administration in stabilized patients during hospitalization after an AHF episode, with the aim of improving care efficiency and clinical outcome.


Assuntos
COVID-19 , Insuficiência Cardíaca , Aminobutiratos , Antagonistas de Receptores de Angiotensina , Compostos de Bifenilo , Combinação de Medicamentos , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Pandemias , Estudos Prospectivos , SARS-CoV-2 , Volume Sistólico , Tetrazóis , Resultado do Tratamento , Valsartana
11.
G Ital Cardiol (Rome) ; 22(10): 861-868, 2021 Oct.
Artigo em Italiano | MEDLINE | ID: mdl-34570121

RESUMO

The triple therapy (angiotensin-converting enzyme [ACE] inhibitors or angiotensin receptor blockers, beta-blockers, mineralocorticoid receptor antagonists) certificated by the 2012 guidelines for symptomatic patients with heart failure and reduced ejection fraction, reaffirmed in the following document of 2016 with the introduction of angiotensin receptor-neprilysin inhibitors (ARNI), has not yet reached an adequate implementation in clinical practice (where the majority of patients is only treated with the double treatment of ACE-inhibitors or angiotensin receptor blockers and beta-blockers). Among the reasons for this general failure, we should consider the enrollment of unselected cases from the real world, without exclusion criteria for age, comorbidity and stage of the disease, the therapeutic inertia of many cardiologists and not least the clinical and organizational complexity of the conventional scheme of implementation of therapy indicated by the guidelines. Not only the prescription of triple therapy is inadequate, but also the "target doses" defined by the large randomized controlled trials should be considered unrealistic in the majority of patients, who often achieve a therapeutic effect at lower doses, generally better tolerated ("target effect"). The new guidelines forthcoming will certify a further step forward with the quadruple therapy (sodium-glucose co-transporter 2 inhibitors, ARNI, beta-blockers and mineralocorticoid receptor antagonists), underlining how a fourfold intervention with different pharmacological mechanisms is able to determine the greatest benefits in patients with systolic heart failure. The discussion is open on the possibility of simplifying and speeding up the conventional implementation scheme of treatment, exploiting the ability of all these pharmacological principles to exert a significant and rapid favorable effect on prognosis already at a low dose in the first 4-8 weeks of treatment.


Assuntos
Antagonistas de Receptores de Angiotensina , Insuficiência Cardíaca , Inibidores da Enzima Conversora de Angiotensina , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Volume Sistólico
12.
J Assoc Physicians India ; 69(6): 11-12, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34472787

RESUMO

BACKGROUND: The present study intended to estimate the comorbidities and risk factors among patients with hypertension in India. Further, the current practice of hypertension management was evaluated and the choice of therapy was assessed based on hypertension grade, risk factors, and comorbidities. METHODS: Electronic medical record data (June 2017-June 2019) of Indian adult hypertensive patients (≥140/90 mmHg) who had two blood pressure (BP) readings were retrospectively analyzed. Demographic characteristics, BP readings, comorbidities, medications and co-medications, and laboratory data were collected at baseline. Grids based on hypertension grade (I, II, and III), demographic factors, risk factors, and comorbidities were created and prescribed antihypertensive drugs (AHDs) in each grid were evaluated. RESULTS: Among 100,075 patients, the proportion of patients in 18-40 year, 40-65 year, and >65 year age groups were 11.4%, 65.1%, and 23.4%, respectively. Proportion of men and women was similar (52.0% vs 47.9%). Proportion of patients with BMI <25 Kg/m2 was 8.1%, 25-29.9 Kg/m2 was 11.9%, and >30 Kg/m2 was 8.8%. Mean BP of patients with hypertension was: grade I (145.05/90.73 mmHg), grade II (160.07/95.64 mmHg), and grade III (180.82/102.76 mmHg). Mean low density lipoprotein (113.26 mg/dL), serum creatinine (2.28 mg/dL), mean HbA1c (8.7%) levels were highest among patients with grade III hypertension. Commonly observed comorbidities were type 2 diabetes mellitus (T2DM: 51.5%), dyslipidemia (36.4%), and chronic kidney disease (CKD: 4.4%). Top concomitant medications included anti-diabetic therapies (34.6%), drugs for dyslipidemia (30.0%), and anti-platelet therapies (6.9%). CONCLUSION: Most prescribed AHD monotherapies were angiotensin receptor II blockers (ARBs) and calcium channel blockers (CCBs) and most prescribed combination therapies were ARBs + diuretics and ARBs + CCBs. Telmisartan and amlodipine+telmisartan for patients with comorbid T2DM or dyslipidemia and metoprolol for those with coronary artery disease were the commonly prescribed AHDs.


Assuntos
Diabetes Mellitus Tipo 2 , Hipertensão , Adolescente , Adulto , Idoso , Antagonistas de Receptores de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Morbidade , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
13.
Medicine (Baltimore) ; 100(35): e26544, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34477114

RESUMO

BACKGROUND: To lower albuminuria and to achieve blood pressure (BP) goals, dual renin-angiotensin-aldosterone system (RAAS) inhibitors are sometimes used in clinical practice for the treatment of CKD. However, the efficacy and safety of dual RAAS blockade therapy remains controversial. METHODS: PubMed, EMBASE, and Cochrane Library were searched, and random effects model was used to calculate the effect sizes of eligible studies. Potential sources of heterogeneity were detected by meta-regression and subgroup analysis. RESULTS: The present meta-analysis of 72 randomized controlled trials with 10,296 patients demonstrated that dual RAAS blockade therapy was superior to monotherapy in reducing the urine albumin excretion, urine protein excretion, and BP. These beneficial effects were related to the decrease of glomerular filtration rate, the increase of serum potassium level, and higher rates of hyperkalemia and hypotension. Meanwhile, these effects did not lead to improvements in short-term or long-term outcomes, including doubling of serum creatinine, acute kidney injury, end-stage renal disease, mortality, and hospitalization. Compared with the single therapy, angiotensin-converting enzyme inhibitor (ACEI) in combination with angiotensin-receptor blocker (ARB) was a better dual therapy than ACEI or ARB in combination with renin inhibitor or aldosterone receptor antagonist in decreasing urine albumin excretion, urine protein excretion and BP, and the combination was not associated with a lower glomerular filtration rate. CONCLUSION: Compared with the single therapy, ACEI in combination with ARB was a better dual therapy than ACEI or ARB in combination with renin inhibitor or aldosterone receptor antagonist. Although ACEI in combination with ARB was associated with higher incidences of hyperkalemia and hypotension, careful individualized management and potassium binders may further expand its application (PROSPERO number CRD42020179398).


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Insuficiência Renal Crônica/tratamento farmacológico , Sistema Renina-Angiotensina/efeitos dos fármacos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Insuficiência Renal Crônica/fisiopatologia
14.
Water Sci Technol ; 84(5): 1182-1189, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34534115

RESUMO

Considering high concentrations of multidrug-resistant bacteria and antibiotic resistance genes (ARGs) in wastewater, agricultural reuse of treated wastewater may be a public health threat due to ARG dissemination in different environmental compartments, including soil and edible parts of crops. We investigated the presence of antibiotic-resistant Escherichia coli as an indicator bacterium from secondary treated wastewater (STWW), water- or wastewater-irrigated soil and crop samples. ARGs including blaCTX-m-32, blaOXA-23, tet-W, sul1, cml-A, erm-B, along with intI1 gene in E. coli isolates were detected via molecular methods. The most prevalent ARGs in 78 E. coli isolates were sul1 (42%), followed by blaCTX-m-32 (19%), and erm-B (17%). IntI1 as a class 1 integrons gene was detected in 46% of the isolates. Cml-A was detected in STWW isolates but no E. coli isolate from wastewater-irrigated soil and crop samples contained this gene. The results also showed no detection of E. coli in water-irrigated soil and crop samples. Statistical analysis showed a correlation between sul1 and cml-A with intI1. The results suggest that agricultural reuse of wastewater may contribute to the transmission of antibiotic-resistant bacteria to soil and crop. Further research is needed to determine the potential risk of ARB associated with the consumption of wastewater-irrigated crops.


Assuntos
Integrons , Águas Residuárias , Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina , Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla , Escherichia coli/genética , Genes Bacterianos , Integrons/genética
15.
Artigo em Inglês | MEDLINE | ID: mdl-34493495

RESUMO

INTRODUCTION: People with type 2 diabetes (T2D) have an increased rate of hospitalization and mortality related to COVID-19. To identify ahead of time those who are at risk of developing severe diseases and potentially in need of intensive care, we investigated the independent associations between longitudinal glycated hemoglobin (HbA1c), the impact of common medications (metformin, insulin, ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), and corticosteroids) and COVID-19 severity in people with T2D. RESEARCH DESIGN AND METHODS: Retrospective cohort study was conducted using deidentified claims and electronic health record data from the OptumLabs Data Warehouse across the USA between January 2017 and November 2020, including 16 504 individuals with T2D and COVID-19. A univariate model and a multivariate model were applied to evaluate the association between 2 and 3-year HbA1c average, medication use between COVID-19 diagnosis and intensive care unit admission (if applicable), and risk of intensive care related to COVID-19. RESULTS: With covariates adjusted, the HR of longitudinal HbA1c for risk of intensive care was 1.12 (per 1% increase, p<0.001) and 1.48 (comparing group with poor (HbA1c ≥9%) and adequate glycemic control (HbA1c 6%-9%), p<0.001). The use of corticosteroids and the combined use of insulin and metformin were associated with significant reduction of intensive care risk, while ACEIs and ARBs were not associated with reduced risk of intensive care. CONCLUSIONS: Two to three-year longitudinal glycemic level is independently associated with COVID-19-related severity in people with T2D. Here, we present a potential method to use HbA1c history, which presented a stronger association with COVID-19 severity than single-point HbA1c, to identify in advance those more at risk of intensive care due to COVID-19 in the T2D population. The combined use of metformin and insulin and the use of corticosteroids might be significant to prevent patients with T2D from becoming critically ill from COVID-19.


Assuntos
COVID-19 , Diabetes Mellitus Tipo 2 , Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Teste para COVID-19 , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Humanos , Estudos Retrospectivos , SARS-CoV-2
17.
BMJ Open ; 11(9): e053393, 2021 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-34531225

RESUMO

OBJECTIVES: The widespread use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) by patients with chronic conditions raised early concerns on the potential exacerbation of COVID-19 severity and fatality. Previous studies addressing this question have used standard methods that may lead to biased estimates when analysing hospital data because of the presence of competing events and event-related dependency. We investigated the association of ACEIs/ARBs' use with COVID-19 disease outcomes using time-to-event data in a multistate setting to account for competing events and minimise bias. SETTING: Nationwide surveillance data from 119 Belgian hospitals. PARTICIPANTS: Medical records of 10 866 patients hospitalised from 14 March 2020to 14 June 2020 with a confirmed SARS-CoV-19 infection and information about ACEIs/ARBs' use. PRIMARY OUTCOME MEASURE: Multistate, multivariate Cox-Markov models were used to estimate the hazards of patients transitioning through health states from admission to discharge or death, along with transition probabilities calculated by combining the baseline cumulative hazard and regression coefficients. RESULTS: After accounting for potential confounders, there was no discernable association between ACEIs/ARBs' use and transfer to intensive care unit (ICU). Contrastingly, for patients without ICU transfer, ACEIs/ARBs' use was associated with a modest increase in recovery (HR 1.07, 95% CI 1.01 to 1.13, p=0.027) and reduction in fatality (HR 0.83, 95% CI 0.75 to 0.93, p=0.001) transitions. For patients transferred to ICU admission, no evidence of an association between ACEIs/ARBs' use and recovery (HR 1.16, 95% CI 0.97 to 1.38, p=0.098) or in-hospital death (HR 0.91, 95% CI 0.73 to 1.12, p=0.381) was observed. Male gender and older age were significantly associated with higher risk of ICU admission or death. Chronic cardiometabolic comorbidities were also associated with less recovery. CONCLUSIONS: For the first time, a multistate model was used to address magnitude and direction of the association of ACEIs/ARBs' use on COVID-19 progression. By minimising bias, this study provided a robust indication of a protective, although modest, association with recovery and survival.


Assuntos
COVID-19 , Hipertensão , Idoso , Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Bélgica/epidemiologia , Mortalidade Hospitalar , Hospitais , Humanos , Masculino , SARS-CoV-2
19.
Bioorg Med Chem ; 48: 116389, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34543844

RESUMO

With the emergence of the third infectious and virulent coronavirus within the past two decades, it has become increasingly important to understand how the virus causes infection. This will inform therapeutic strategies that target vulnerabilities in the vital processes through which the virus enters cells. This review identifies enzymes responsible for SARS-CoV-2 viral entry into cells (ACE2, Furin, TMPRSS2) and discuss compounds proposed to inhibit viral entry with the end goal of treating COVID-19 infection. We argue that TMPRSS2 inhibitors show the most promise in potentially treating COVID-19, in addition to being a pre-existing medication with fewer predicted side-effects.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Enzima de Conversão de Angiotensina 2/antagonistas & inibidores , Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , Inibidores de Janus Quinases/uso terapêutico , SARS-CoV-2/efeitos dos fármacos , Animais , Combinação de Medicamentos , Humanos , Metotrexato/uso terapêutico , Receptores de Angiotensina/metabolismo , Transdução de Sinais/efeitos dos fármacos
20.
J Assoc Physicians India ; 69(8): 11-12, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34472802

RESUMO

AIMS AND OBJECTIVES: To study the incidence,risk factors and in hospital mortality of Type I Cardiorenal syndrome(CRS1). To study the incidence of hyperkalemia in patients receiving Acei, ARB's or MRA Materials and Methods: Prospective observational cohort study done between June and December 2015 in Madras Medical Mission, Chennai. Consecutive patients admitted with ACS/ADHF were studied and clinical, biochemical and laboratory data was collected. The development of CRS1 was determined by KDIGO criteria. Statistical analysis was done using IBM SPSS version 21. RESULTS: Among 460 patients studied, 153 (34%) developed CRS 1 according to KDIGO criteria. The number of diabetics and patients with pre-existing CKD was significantly higher in the CRS 1 group (p=0.00). Mortality was significantly higher in the CRS 1 group (20.2% vs. 7.8% p=0.00). The presence of CKD, Diabetes mellitus, inotropic requirement and eGFR, 60 ml/min/1.73 m2 were significant predictors of CRS 1. Among patients with CRS1, 55 patients (23.5%) needed renal replacement therapy (15.6 % acute peritoneal dialysis, 20.2% SLED). There was no significant difference in the incidence of hyperkalemia in patients who were on prior Acei, ARBs and MRA. CONCLUSION: There is a high incidence of CRS 1 in our setting and the mortality is significantly higher in this group of patients. Early nephrology referral and prompt stoppage of nephrotoxic agents can significantly reduce the incidence and risk of CRS1.


Assuntos
Síndrome Cardiorrenal , Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina , Síndrome Cardiorrenal/epidemiologia , Síndrome Cardiorrenal/terapia , Humanos , Índia/epidemiologia , Estudos Prospectivos , Fatores de Risco , Atenção Terciária à Saúde
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