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1.
Blood Press ; 33(1): 2368800, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38910347

RESUMO

Objective Real-life management of patients with hypertension and chronic kidney disease (CKD) among European Society of Hypertension Excellence Centres (ESH-ECs) is unclear : we aimed to investigate it. Methods A survey was conducted in 2023. The questionnaire contained 64 questions asking ESH-ECs representatives to estimate how patients with CKD are managed. Results Overall, 88 ESH-ECS representatives from 27 countries participated. According to the responders, renin-angiotensin system (RAS) blockers, calcium-channel blockers and thiazides were often added when these medications were lacking in CKD patients, but physicians were more prone to initiate RAS blockers (90% [interquartile range: 70-95%]) than MRA (20% [10-30%]), SGLT2i (30% [20-50%]) or (GLP1-RA (10% [5-15%]). Despite treatment optimisation, 30% of responders indicated that hypertension remained uncontrolled (30% (15-40%) vs 18% [10%-25%]) in CKD and CKD patients, respectively). Hyperkalemia was the most frequent barrier to initiate RAS blockers, and dosage reduction was considered in 45% of responders when kalaemia was 5.5-5.9 mmol/L. Conclusions RAS blockers are initiated in most ESH-ECS in CKD patients, but MRA and SGLT2i initiations are less frequent. Hyperkalemia was the main barrier for initiation or adequate dosing of RAS blockade, and RAS blockers' dosage reduction was the usual management.


What is the context? Hypertension is a strong independent risk factor for development of chronic kidney disease (CKD) and progression of CKD to ESKD. Improved adherence to the guidelines in the treatment of CKD is believed to provide further reduction of cardiorenal events. European Society of Hypertension Excellence Centres (ESH-ECs) have been developed in Europe to provide excellency regarding management of patients with hypertension and implement guidelines. Numerous deficits regarding general practitioner CKD screening, use of nephroprotective drugs and referral to nephrologists prior to referral to ESH-ECs have been reported. In contrast, real-life management of these patients among ESH-ECs is unknown. Before implementation of strategies to improve guideline adherence in Europe, we aimed to investigate how patients with CKD are managed among the ESH-ECs.What is the study about? In this study, a survey was conducted in 2023 by the ESH to assess management of CKD patients referred to ESH-ECs. The questionnaire contained 64 questions asking ESH-ECs representatives to estimate how patients with CKD are managed among their centres.What are the results? RAAS blockers are initiated in 90% of ESH-ECs in CKD patients, but the initiation of MRA and SGLT2i is less frequently done. Hyperkalemia is the main barrier for initiation or adequate dosing of RAAS blockade, and its most reported management was RAAS blockers dosage reduction. These findings will be crucial to implement strategies in order to improve management of patients with CKD and guideline adherence among ESH-ECs.


Assuntos
Hipertensão , Insuficiência Renal Crônica , Humanos , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Hipertensão/tratamento farmacológico , Europa (Continente) , Anti-Hipertensivos/uso terapêutico , Masculino , Inquéritos e Questionários , Feminino , Pessoa de Meia-Idade , Bloqueadores dos Canais de Cálcio/uso terapêutico , Sociedades Médicas , Antagonistas de Receptores de Angiotensina/uso terapêutico
3.
J Hypertens ; 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38747416

RESUMO

OBJECTIVE: Real-life management of hypertensive patients with chronic kidney disease (CKD) is unclear. METHODS: A survey was conducted in 2023 by the European Society of Hypertension (ESH) to assess management of CKD patients referred to ESH-Hypertension Excellence Centres (ESH-ECs) at first referral visit. The questionnaire contained 64 questions with which ESH-ECs representatives were asked to estimate preexisting CKD management quality. RESULTS: Overall, 88 ESH-ECs from 27 countries participated (fully completed surveys: 66/88 [75.0%]). ESH-ECs reported that 28% (median, interquartile range: 15-50%) had preexisting CKD, with 10% of them (5-30%) previously referred to a nephrologist, while 30% (15-40%) had resistant hypertension. The reported rate of previous recent (<6 months) estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (UACR) testing were 80% (50-95%) and 30% (15-50%), respectively. The reported use of renin-angiotensin system blockers was 80% (70-90%). When a nephrologist was part of the ESH-EC teams the reported rates SGLT2 inhibitors (27.5% [20-40%] vs. 15% [10-25], P = 0.003), GLP1-RA (10% [10-20%] vs. 5% [5-10%], P = 0.003) and mineralocorticoid receptor antagonists (20% [10-30%] vs. 15% [10-20%], P = 0.05) use were greater as compared to ESH-ECs without nephrologist participation. The rate of reported resistant hypertension, recent eGFR and UACR results and management of CKD patients prior to referral varied widely across countries. CONCLUSIONS: Our estimation indicates deficits regarding CKD screening, use of nephroprotective drugs and referral to nephrologists before referral to ESH-ECs but results varied widely across countries. This information can be used to build specific programs to improve care in hypertensives with CKD.

4.
J Comp Eff Res ; 12(4): e220181, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36891969

RESUMO

Aim: This online interactive survey investigated lipid-lowering approaches of French cardiologists in high- and very high-cardiovascular risk patients with hypercholesterolemia. Materials & methods: Physicians assessed three hypothetical patients at three clinic visits, and selected the patients' cardiovascular risk category, target low-density lipoprotein cholesterol (LDL-C) and treatment. Results: A total of 162 physicians completed 480 risk assessments; 58% of assessments correctly categorized the hypothetical patients. Most physicians chose the correct LDL-C target for one of the very high-risk patients, but higher-than-recommended targets were selected for the other very high-risk patient and the high-risk patient. Statins were the most commonly chosen treatment. Conclusion: French cardiologists often underestimate cardiovascular risk in patients with hypercholesterolemia, select a higher-than-recommended LDL-C target and prescribe less intensive treatment than that recommended by guidelines.


Assuntos
Anticolesterolemiantes , Cardiologistas , Inibidores de Hidroximetilglutaril-CoA Redutases , Hipercolesterolemia , Humanos , Hipercolesterolemia/complicações , Hipercolesterolemia/tratamento farmacológico , LDL-Colesterol , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , França , Anticolesterolemiantes/uso terapêutico
5.
Hypertension ; 80(5): 901-911, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36748474

RESUMO

Drugs acting by inhibition of the angiogenic action of VEGF (vascular endothelial growth factor) have become major instruments in the treatment of cancer. The downside of their favorable effects in cancer treatment is their frequent cardiovascular side effects. The most consistent finding thus far on the cardiovascular side effects of VEGF inhibitors is the high incidence of hypertension. In this short review, we discuss the evidence that hypertension occurring during VEGF inhibitor treatment is caused by microvascular rarefaction. After a review of the role of VEGF in microvascular growth and differentiation, we present evidence from studies in experimental models of hypertension as well as clinical studies on the microvascular network changes during and after VEGF inhibitor treatment.


Assuntos
Hipertensão , Rarefação Microvascular , Neoplasias , Humanos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Rarefação Microvascular/induzido quimicamente , Rarefação Microvascular/complicações , Rarefação Microvascular/tratamento farmacológico , Fatores de Crescimento do Endotélio Vascular , Neoplasias/tratamento farmacológico , Inibidores da Angiogênese/efeitos adversos
6.
J Hypertens ; 41(3): 508-515, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36633311

RESUMO

OBJECTIVE: The aim of this study was to assess the reduction in all-cause death and cardiovascular outcomes associated with the administration of the thiazide-like diuretic indapamide monotherapy or in combination with perindopril as a blood pressure lowering drug in randomized controlled trials (RCTs). METHOD: Aggregate data from four published RCTs conducted versus matching placebo were pooled: PATS, a 2-year study (indapamide), and PROGRESS, a 4-year study (indapamide and perindopril), both in patients with a history of stroke or transient ischemic attack; ADVANCE, a 4-year study in patients with type 2 diabetes and cardiovascular risk factor (single-pill combination perindopril/indapamide) and HYVET, a 2-year study in very elderly hypertensive individuals (indapamide and an option of perindopril). The pooled effect (fixed and random) estimate (hazard ratio) was reported with corresponding 95% confidence intervals and P values. Treatment discontinuations were also analysed to assess the net benefit of the treatment. RESULTS: The population involved 24 194 patients (active: 12 113, placebo: 12 081). The fixed-effects meta-analysis of the three mortality endpoints found low statistical heterogeneity ( I2  = 0). Statistically significant risk reductions in the indapamide with or without perindopril-treated patients as compared to placebo were observed for all-cause death (-15%), cardiovascular death (-21%), fatal stroke (-36%) and all strokes (-27%). Other cardiovascular outcomes were improved (risk reduction, 22 to 36%). As expected, discontinuation rates for safety (two studies) were higher in the active group (6.4 vs. 3.9%), while they were similar when discontinuation for any reason is concerned (18.4 vs. 18.0%). CONCLUSION: Across medium to high cardiovascular risk population, long-term indapamide, mostly combined with perindopril-based treatment, provided evidence of benefit on mortality and morbidity.


Assuntos
Hipertensão , Indapamida , Acidente Vascular Cerebral , Humanos , Idoso , Perindopril/uso terapêutico , Indapamida/uso terapêutico , Anti-Hipertensivos , Hipertensão/complicações , Acidente Vascular Cerebral/epidemiologia , Combinação de Medicamentos , Pressão Sanguínea , Ensaios Clínicos Controlados Aleatórios como Assunto
7.
PLoS One ; 17(10): e0275337, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36251660

RESUMO

Type 2 diabetes (T2D) induces hyperglycemia, alters hemoglobin (Hb), red blood cell (RBC) deformability and impairs hemorheology. The question remains whether RBC breakdown and intravascular hemolysis (IVH) occur in T2D patients. We characterized RBC-degradation products and vesiculation in a case-control study of 109 T2D patients and 65 control subjects. We quantified heme-related absorbance by spectrophotometry and circulating extracellular vesicles (EV) by flow cytometry and electron microscopy. Heme-related absorbance was increased in T2D vs. control plasma (+57%) and further elevated in obese T2D plasma (+27%). However, large CD235a+ EV were not increased in T2D plasma. EV from T2D plasma, or shed by isolated T2D RBC, were notably smaller in diameter (-27%) and carried heme-related absorbance. In T2D plasma, higher heme-related absorbance (+30%) was associated to peripheral sensory neuropathy, and no other vascular complication. In vitro, T2D RBC-derived EV triggered endothelial stress and thrombin activation in a phosphatidylserine- and heme-dependent fashion. We concluded that T2D was associated with low-grade IVH. Plasma absorbance may constitute a novel biomarker of peripheral neuropathy in T2D, while flow cytometry focusing on large EV may be maladapted to characterize RBC EV in T2D. Moreover, therapeutics limiting IVH or neutralizing RBC breakdown products might bolster vasculoprotection in T2D.


Assuntos
Diabetes Mellitus Tipo 2 , Traumatismos dos Nervos Periféricos , Biomarcadores/metabolismo , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Eritrócitos/metabolismo , Heme/metabolismo , Hemoglobinas/metabolismo , Hemólise , Humanos , Traumatismos dos Nervos Periféricos/metabolismo , Fosfatidilserinas/metabolismo , Trombina/metabolismo
9.
J Clin Pharm Ther ; 47(8): 1212-1217, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35352367

RESUMO

WHAT IS KNOWN AND OBJECTIVE: This study aimed to determine the results of INR monitoring in patients on vitamin K antagonists (VKAs) and the time in therapeutic range (TTR) in 'real-world' settings. METHODS: Retrospective analysis of 836,857 INR measurements performed in adults from February 2010 to August 2015 in two districts in the French Brittany region. RESULTS: Of the 836,857 INR measurements, 94.9% were ordered by general practitioners and 2.0% by cardiologists. The number of tests increased by 10-year age categories up to the age-group of 80-90 years. The number of INR measurements increased from 169,636 in 2011 to 176,184 in 2012, but then decreased slightly to 162,597 in 2013 and 164,427 in 2014. Mean coefficient of variation of INR was 19.0%, and mean TTR was 29.0%. TTR was higher in women than in men (31% vs. 18%), in older than in younger patients (19.1% at 40 years and 38.6% at 100 years) and in patients with arrhythmias than in those with deep vein thrombosis/pulmonary embolism (44.4% versus 19.4%) (p < 10-5 for each comparison). Median interval between INR measurements was 14 days [7-28]; it was prolonged in men vs women, rural vs urban regions, older vs younger patients and when requested by GPs vs cardiologists. The interval was shorter for patients with INR outside the therapeutic range versus patients with INR within the therapeutic range (9 days [5-21] vs. 18 days [10-29], p < 10-10 ). WHAT IS NEW AND CONCLUSION: VKAs are still frequently prescribed in this era of direct oral anticoagulants. The low TTR cannot be explained by inadequate INR monitoring.


Assuntos
Fibrilação Atrial , Vitamina K , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Análise de Dados , Feminino , Fibrinolíticos/uso terapêutico , Humanos , Coeficiente Internacional Normatizado , Masculino , Estudos Retrospectivos
10.
JMIR Form Res ; 6(3): e32725, 2022 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-35293869

RESUMO

BACKGROUND: Noncommunicable disease (NCD)-related deaths account for 71% of deaths worldwide. The World Health Organization recently developed a global action plan to address the impact of NCDs, with the goal of reducing the number of premature NCD-related deaths to 25% by the year 2025. Appropriate therapeutic adherence is critical for effective disease management; however, approximately 30%-50% of patients with an NCD do not comply with disease management activities as prescribed. Web-based patient communities can represent platforms from which specific information on patients' perception of treatment adherence can be gathered outside of a clinical trial setting. OBJECTIVE: This study aims to better understand patients' perspectives regarding therapeutic adherence and iatrogenic risk in 2 major groups of NCDs for which poor disease management can have fatal consequences: cardiovascular diseases and mental disorders. Therapeutic adherence, motivational factors, patients' awareness and perception of iatrogenesis, and treatment tools used by patients were assessed. METHODS: A web-based survey was performed among patients with cardiovascular diseases or mental disorders or both conditions who were registered on the French Carenity platform, a web-based community in which patients with an NCD can share experiences and receive support and information. The study inclusion criteria were defined as follows: diagnosis of cardiovascular disease or mental disorder or both conditions (self-declared), age ≥18 years, residence in France, registration on the French Carenity platform, and ongoing pharmaceutical treatment for the condition. Patients who met the inclusion criteria were then invited to complete a self-administered web-based questionnaire that included questions addressing therapeutic adherence and iatrogenic risk. RESULTS: A total of 820 patients were enrolled in the study, including patients with cardiovascular diseases (403/820, 49.2%), patients with mental disorders (292/820, 35.6%), and patients with both cardiovascular diseases and mental disorders (125/820, 15.2%). The mean age of the participants was 55.2 (SD 12.7) years. We found that 82.8% (679/820) of patients experienced adverse effects of medication. Patients tended to perceive themselves to be more adherent than they actually were; a significant number of patients disregarded their prescription and stopped or interrupted medication without consulting with a doctor. Patients with cardiovascular diseases were nearly twice as adherent as patients with a mental disorder (P≤.001). Adherence was significantly associated with gender (P≤.001), age (P≤.001), and treatment complexity (P≤.001). Finally, for each disease type, 3 patient profiles were identified, which provide interesting insight for improving therapeutic adherence and adjustment strategies specifically according to patient behavior. CONCLUSIONS: This study provides insight into the perspectives of patients receiving therapy for cardiovascular diseases or mental disorders or both conditions, which could help improve the management of NCDs and prevent premature death. Our study also shows that web-based patient platforms provide new opportunities to improve disease management by understanding patients' experiences.

11.
Telemed J E Health ; 28(2): 266-270, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34101507

RESUMO

Introduction: Despite widespread investigation into the incidence of acute myocardial infarction during the coronavirus disease 2019 (COVID-19) pandemic and associated lockdown, no study has examined the situation's impact on blood pressure (BP) levels. Methods: Measurements of BP and heart rate (HR) were obtained from persons living in the Paris urban area using connected home BP monitors (accessible to patients and health providers through a secured server). Three time periods of e-health recordings were compared: during the pandemic before the lockdown, during the lockdown, and the same time period in 2019. Results: A total of 297,089 BP recordings from 2,273 participants (age 56.3 ± 12.8 years, 81.1% male) were made. During confinement, systolic BP gradually decreased by 3 mmHg (-2.4 to -3.9), and diastolic BP by 1.5 mmHg (-1.4 to -2.2) (all p < 0.001); this decrease was greater for participants with higher BP (p < 0.0001 each). No significant variation in HR was noted. Conclusion: Among a very large cohort, we observed a significant decrease in home BP measured with e-health devices during the first lockdown period. This study emphasizes the research potential of e-health during the COVID-19 crisis.


Assuntos
COVID-19 , Telemedicina , Adulto , Idoso , Pressão Sanguínea , Controle de Doenças Transmissíveis , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , SARS-CoV-2
12.
Am J Hypertens ; 35(4): 293-302, 2022 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-34265036

RESUMO

Despite a similar beneficial effect on blood pressure lowering observed with angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type 1 receptor (AT1R) blocker (ARBs), several clinical trials and meta-analyses have reported higher cardiovascular mortality and lower protection against myocardial infarction with ARBs when compared with ACEIs. The European guidelines for the management of coronary syndromes and European guidelines on diabetes recommend using ARBs in patients who are intolerant to ACEIs. We reviewed the main pharmacological differences between ACEIs and ARBs, which could provide insights into the differences in the cardiac protection offered by these 2 drug classes. The effect of ACEIs on the tissue and plasma levels of bradykinin and on nitric oxide production and bioavailability is specific to the mechanism of action of ACEIs; it could account for the different effects of ACEIs and ARBs on endothelial function, atherogenesis, and fibrinolysis. Moreover, chronic blockade of AT1 receptors by ARBs induces a significant and permanent increase in plasma angiotensin II and an overstimulation of its still available receptors. In animal models, AT4 receptors have vasoconstrictive, proliferative, and inflammatory effects. Moreover, in models with kidney damage, atherosclerosis, and/or senescence, activation of AT2 receptors could have deleterious fibrotic, vasoconstrictive, and hypertrophic effects and seems prudent and reasonable to reserve the use of ARBs for patients who have presented intolerance to ACE inhibitors.


Assuntos
Inibidores da Enzima Conversora de Angiotensina , Renina , Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Antagonistas de Receptores de Angiotensina/efeitos adversos , Antagonistas de Receptores de Angiotensina/farmacologia , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Angiotensinas , Humanos , Sistema Renina-Angiotensina/efeitos dos fármacos
13.
Ann Biol Clin (Paris) ; 79(5): 456-459, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34782311

RESUMO

Babesiosis is a tick-borne infectious disease, caused by an intraerythrocytic parasite of the genus Babesia. It has clinical, biological and microbiological similarities with Plasmodium related infections. In rare cases, babesiosis may be complicated by hemophagocytic lymphohistiocytosis, which occurs preferentially in the immunodeficient patient. We report here the case of a non-immunocompromised patient living in Manhattan, New York hospitalized for a complicated babesiosis of a hemophagocytic lymphohistiocytosis. After 7 days of hospitalization and treatment by azithromycin 500 mg/day and atovaquone 750 mg twice a day, the patient was discharged with an improvement in clinical symptoms and biological parameters.


Assuntos
Babesia , Babesiose , Atovaquona/uso terapêutico , Azitromicina/uso terapêutico , Babesiose/complicações , Babesiose/diagnóstico , Babesiose/tratamento farmacológico , Humanos
15.
Patient Prefer Adherence ; 15: 1739-1753, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34408407

RESUMO

PURPOSE: Some patients make a rational choice not to follow medical prescriptions; others fail to take their medications for reasons beyond their control, such as mere forgetfulness or a weak medication routine. The aim of this study was to elucidate the functioning of patient intentionality in medication adherence. PATIENTS AND METHODS: This online study was conducted in metropolitan France in 2019. A cross-sectional survey of 50 questions was conducted with 3001 respondents diagnosed with diabetes, hypertension, and/or hypercholesterolemia identified from a panel of 54,000 people. These questions included a validated six-item questionnaire to detect nonadherence, two questions to detect intentional nonadherence by patients, and three questions on the effects of habit. Our questionnaire also included questions on the feelings of respondents regarding their doctor's attitude to their problems and needs, their trust in general practitioners (GP) and specialists, their sense of being involved in treatment decisions, and the influence of side effects and habits on patients' adherence. This study used the strategy of focusing on strictly adherent patients in the hope of finding ways to improve adherence. For this reason, we defined adherence as the absence of a positive response to the 6-item nonadherence screening questionnaire. RESULTS: Of 3001 respondents, 1804 were diagnosed with hypertension, 1458 with hypercholesterolemia, and 774 with diabetes. Of the total number of patients, 72% were afflicted with one disease, 21% with two ailments, and 7% with three simultaneous illnesses. One-third (33%) of the patients did not tender a positive answer to the adherence questionnaire and were deemed adherent. 1) Thirty-two percent of the patients reported occasionally omitting their medication deliberately, and 84% said they had a reason for missing doses. These statements suggesting intentional nonadherence were negatively associated with adherence as identified via multivariate analysis (P = 0.0012 and P < 0.0001, for the first and second statement, respectively). 2) Univariate analyses revealed strong associations (P < 0.0001) between strict adherence on one hand and lack of intentional nonadherence, patient age, absence of drug side effects, taking drugs by habit, feeling involved in treatment decisions, getting information about treatment, and disease, and trust in doctors, on the other hand. 3) Specifically, univariate analysis of the absence of reported side effects revealed strong associations (P < 0.0001) with adequate information about medicines and diseases and trust in GP. These original data were consistent with the concept of the nocebo effect. 4) We observed a strong association between the absence of intentional nonadherence (statement of never deliberately missing medication) and respondent statements about generally sticking to the routine (P < 0.0001), ie, "I take my medication because I am used to taking it." This important result suggests that patients are strictly adherent in two ways: the absence of intentional nonadherence and reliance on habit, which we term as "unintentional adherence." 5) Finally, a multiple correspondence analysis illustrated all statistically significant relationships found in this study. CONCLUSION: We present a new global model of adherence in which patient adherence was improved both by reducing intentional nonadherence and by promoting the abovementioned unintentional adherence by habit. This model highlights the role of shared decision-making and the trust felt by patients in their doctors. These results could exert a major impact on medical practice and education by demonstrating the importance of physicians' attitudes, involving the patient in decisions (shared decision-making), offering information about medicines and diseases (patient education), understanding the problems of patients, and taking their needs into account (empathy). The development of these attitudes should be an important aspect of the medical curricula.

17.
Biochimie ; 189: 51-64, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34153377

RESUMO

The infectious power of coronaviruses is dependent on cholesterol present in the membranes of their target cells. Indeed, the virus enters the infected cell either by fusion or by endocytosis, in both cases involving cholesterol-enriched membrane microdomains. These membrane domains can be disorganized in-vitro by various cholesterol-altering agents, including statins that inhibit cell cholesterol biosynthesis. As a consequence, numerous cell physiology processes, such as signaling cascades, can be compromised. Also, some examples of anti-bacterial and anti-viral effects of statins have been observed for infectious agents known to be cholesterol dependent. In-vivo, besides their widely-reported hypocholesterolemic effect, statins display various pleiotropic effects mediated, at least partially, by perturbation of membrane microdomains as a consequence of the alteration of endogenous cholesterol synthesis. It should thus be worth considering a high, but clinically well-tolerated, dose of statin to treat Covid-19 patients, in the early phase of infection, to inhibit virus entry into the target cells, in order to control the viral charge and hence avoid severe clinical complications. Based on its efficacy and favorable biodisposition, an option would be considering Atorvastatin, but randomized controlled clinical trials are required to test this hypothesis. This new therapeutic proposal takes benefit from being a drug repurposing, applied to a widely-used drug presenting a high efficiency-to-toxicity ratio. Additionally, this therapeutic strategy avoids any risk of drug resistance by viral mutation since it is host-targeted. Noteworthy, the same pharmacological approach could also be proposed to address different animal coronavirus endemic infections that are responsible for heavy economic losses.


Assuntos
Antivirais/uso terapêutico , Atorvastatina/uso terapêutico , Tratamento Farmacológico da COVID-19 , COVID-19 , Colesterol/metabolismo , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Microdomínios da Membrana/metabolismo , SARS-CoV-2/metabolismo , Animais , COVID-19/metabolismo , Humanos
18.
Infect Dis Clin Pract (Baltim Md) ; 29(2): e109-e110, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34191904

RESUMO

During the SARS-CoV-2 pandemic, a variety of dermatological conditions were reported by physicians. Given the context, these lesions have been labeled as secondary to SARS-CoV-2 infection. We report the case of a recurrence of herpes zoster in a patient hospitalized with an SARS-CoV-2 infection. The rash occurred on the 15th day of hospitalization while the patient was recovering from a severe form. Local swab showed the presence of varicella-zoster virus within the vesicles. Dermatological symptoms secondary to COVID-19 have been frequently described. This is the first case that demonstrates the recurrence of herpes zoster during a SARS-CoV-2 infection.

19.
J Hypertens ; 39(8): 1611-1620, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-33710168

RESUMO

OBJECTIVE: To contrast the association between blood pressure (BP) level and antihypertensive medications at hospital admission with 1-year mortality in patients undergoing revascularization for critical limb ischemia (CLI). METHODS: From November 2013 to May 2019, 315 consecutive patients were retrospectively included. A median of seven (IQR 3-13) separate readings were recorded for each patient before revascularization procedure and the average represented patient's mean BP. BP-lowering medications, clinical and biological parameters were recorded at baseline. The main outcome was total 1-year mortality. RESULTS: The cohort included 172 men (55%) and 143 women (45%), with a mean age of 77.9 ±â€Š11.9 years. Treated hypertension was present in 245 (78%) patients; 288 (91%) patients had BP-lowering drug prescriptions (2.1 ±â€Š1.3 medications at baseline). Mean SBP, DBP, mean BP (MBP) and pulse pressure (PP) were 132 ±â€Š18, 70 ±â€Š8, 90 ±â€Š10 and 62 ±â€Š16mmHg. During 1-year follow-up, 80 (25.4%) patients died. In single-pressure multivariate analysis, SBP (hazard ratio 0.97; 95% CI 0.96-0.99; P = 0.005), MBP (hazard ratio 0.96; 95% CI 0.92-0.99; P = 0.01), PP (hazard ratio 0.97; 95% CI 0.95-0.99; P = 0.009), but not DBP, were inversely correlated with 1-year mortality, independently of age, coronary heart disease, left ventricular ejection fraction, brain natriuretic peptide, serum albumin, institutionalized status and antihypertensive drugs. Association between SBP, MBP and PP with 1-year mortality had a quite linear reverse pattern. CONCLUSION: Among patients undergoing revascularization for CLI, there is an inverse correlation between admission SBP, MBP and PP with 1-year mortality. BP may represent a modifiable therapeutic target to prevent poor outcome in CLI patients.


Assuntos
Hipertensão , Função Ventricular Esquerda , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea , Feminino , Humanos , Hipertensão/tratamento farmacológico , Isquemia , Masculino , Estudos Retrospectivos , Fatores de Risco , Volume Sistólico
20.
Int J Infect Dis ; 104: 617-623, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33453395

RESUMO

BACKGROUND: Ceftriaxone and cefotaxime share a similar antibacterial spectrum and similar indications but have different pharmacokinetic characteristics. Ceftriaxone is administered once daily and 40% of its clearance is by biliary elimination, whereas cefotaxime requires three administrations per day and shows less than 10% biliary elimination. The high biliary elimination of ceftriaxone suggests a greater impact of this antibiotic on the gut microbiota than cefotaxime. The objective of this study was to compare the impact of ceftriaxone and cefotaxime on the gut microbiota. METHODS: A prospective clinical trial was performed that included 55 patients treated with intravenous ceftriaxone (1 g/24 h) or cefotaxime (1 g/8 h) for at least 3 days. Three fresh stool samples were collected from each patient (days 0, 3, and 7 or at the end of intravenous treatment) to assess the emergence of third-generation cephalosporin (3GC)-resistant Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae, Pseudomonas aeruginosa, toxigenic Clostridioides difficile, and vancomycin-resistant enterococci. RESULTS: The emergence of 3GC-resistant gram-negative enteric bacilli (Enterobacteriaceae) (5.9% vs 4.7%, p > 0.99), Enterococcus spp, and non-commensal microorganisms did not differ significantly between the groups. Both antibiotics reduced the counts of total gram-negative enteric bacilli and decreased the cultivable diversity of the microbiota, but the differences between the groups were not significant. CONCLUSION: No significant difference was observed between ceftriaxone and cefotaxime in terms of the emergence of resistance.


Assuntos
Antibacterianos/uso terapêutico , Cefotaxima/uso terapêutico , Ceftriaxona/uso terapêutico , Farmacorresistência Bacteriana , Microbioma Gastrointestinal/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Fezes/microbiologia , Feminino , Bactérias Gram-Negativas/efeitos dos fármacos , Hospitalização , Humanos , Masculino , Testes de Sensibilidade Microbiana , Projetos Piloto , Estudos Prospectivos
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