Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 65.286
Filtrar
1.
Pol Merkur Lekarski ; 48(287): 339-343, 2020 Oct 23.
Artigo em Polonês | MEDLINE | ID: mdl-33130795

RESUMO

Hypertensive crisis is a sudden rise in blood pressure with accompanying clinical symptoms. The disease is extremely rare in small children and is always a complication of secondary hypertension. CASE REPORT: 3-year-old boy (spontaneous delivery, 37 week of gestation, birth weight 2170g, 10 AS, unremarkable family history) was admitted to a hospital because of weight loss (1.5 kg, i.e. approx. 15% in 6 months), anorexia, abdominal and limb pain and lethargy. On admission, very high blood pressure values (190/150 mm Hg), lean subcutaneous tissue, frequent blinking, height 88 cm (<3c), body weight 9.5 kg (<3c). In additional tests: blood morphology, parameters of renal function, ions, gasometry, catecholamine urinary excretion, steroid profile and daily cortisol profile were within normal limits. Elevated plasma renin activity was found. In imaging studies kidneys, adrenal glands and renal arteries were normal. Normotension was not obtained on two antihypertensive drugs - metoprolol and amlodipine. In angio-CT tortuous right vertebral artery, extending to the left on the anterolateral surface of the medulla oblongata - possible compression of the vessel of the left side of medulla - was found. Diagnosis of neurovascular conflict was made. The patient was consulted by neurosurgeon who declare no possibility of surgical treatment of anomalies. In the treatment, according to the literature, a drug blocking the renin-angiotensin-aldosterone-enalapril system was used, which normalized blood pressure. At the same time, intensive nutritional treatment was used. Resolution of symptoms and weight gain was observed. In further follow-up patients' parents withdrew enalapril lawlessly, which did not lead to recurrent rise in blood pressure. The latter may suggest other, transient cause of hypertensive crisis e.g. intoxication. CONCLUSIONS: Severe hypertension in pediatric patients can give symptoms as weight loss and behavioral disorders. In the diagnostic of hypertensive crisis in children, neuroimaging studies and toxicological tests should be performed.


Assuntos
Hipertensão , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , Criança , Pré-Escolar , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/etiologia , Masculino , Artéria Renal
2.
Kardiologiia ; 60(7): 28-35, 2020 Aug 11.
Artigo em Russo | MEDLINE | ID: mdl-33155938

RESUMO

Aim To compare results of 24-h treatments with bosentan and macitentan by the clinical functional status and indexes of pulmonary hemodynamics in patients with pulmonary arterial hypertension (PAH).Materials and methods Based on the Russian National Registry (NCT03707561), 44 patients older than 18 years with PAH (34 patients with idiopathic pulmonary hypertension (IPH) and 10 patients with Eisenmenger syndrome) were retrospectively included into this study. Based on the statistical method of pairwise comparison, two groups were formed and matched by age, gender, WHO functional class (FC), and 6-min walk distance (6MWD). 22 patients of group 1 (17 with IPH and 5 with Eisenmenger syndrome) were treated with macitentan 10 mg/day, and 22 patients of group 2 (17 with IPH and 5 with Eisenmenger syndrome) were treated with bosentan 250 mg/day. Clinical instrumental data (6MWD, Borg dyspnea score, chest X-ray, transthoracic echocardiography (EchoCG), and right heart catheterization (RHC)) were evaluated at baseline and after 24 weeks of therapy.Results By week 24 of the treatment, FC and 6MWD improved in both groups. The macitentan treatment was associated with a significant decrease in Borg score. Significant intergroup differences in EchoCG data were not observed. The bosentan treatment was associated with a decrease in right ventricular (RV) dimension and a tendency towards a decrease in calculated pulmonary artery systolic pressure (PASP). By week 24, the macitentan treatment as compared to the bosentan treatment, was associated with a decrease in cardiothoracic ratio (CTR). In both groups, RHC showed decreases in PASP, mean pulmonary artery pressure and pulmonary vascular resistance, and improvements in cardiac output (CO), cardiac index, and stroke volume (SV) values. By week 24, the increase in SV was greater in the macitentan treatment group than in the bosentan treatment group (р=0.05).Conclusion The 24-week treatment with bosentan or macitentan provided significant and comparable improvement of the functional profile in PAH patients with FC II (WHO) at baseline. The decrease in CTR was significantly more pronounced in the macitental treatment group compared to the bosentan treatment group. The 24-week bosentan treatment resulted in a decrease in RV anterior-posterior dimension, a tendency towards a decrease in PASP according to EchoCG data. Macitentan provided more pronounced dynamics of dyspnea than bosentan according to the results of 6MWD test and the increase in SV according to RHC data.


Assuntos
Hipertensão Pulmonar , Hipertensão Arterial Pulmonar , Anti-Hipertensivos/uso terapêutico , Bosentana , Antagonistas dos Receptores de Endotelina/farmacologia , Hipertensão Pulmonar Primária Familiar/tratamento farmacológico , Hemodinâmica , Humanos , Hipertensão Pulmonar/tratamento farmacológico , Pirimidinas , Estudos Retrospectivos , Federação Russa , Sulfonamidas , Resultado do Tratamento
3.
Kardiologiia ; 60(8): 130-140, 2020 Sep 17.
Artigo em Russo | MEDLINE | ID: mdl-33164724

RESUMO

The article discusses results of secondary analysis of the data obtained in the SPRINT study and published in recent years. Unresolved issues in the tactics of managing patients with arterial hypertension are discussed. One of such issues is choosing an optimum level of blood pressure (BP) for a subgroup of patients with certain characteristics, including elderly and senile patients, patients with chronic kidney disease, and patients with arterial hypertension who continue smoking. The article discusses calculation of a threshold of risk for complications of cardiovascular diseases, at which a maximum advantage of intensified regimens of antihypertensive therapy could be achieved. In addition, the article addresses approaches to selection of antihypertensive drugs in the current conditions. The authors discussed the role of candesartan in the treatment of arterial hypertension, a sartan most studied in a broad range of patients. The issue of a rapid increase in BP without a damage to target organs is addressed; evidence for the role of captopril in such clinical situation is provided.


Assuntos
Doenças Cardiovasculares , Hipertensão , Idoso , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , Captopril/farmacologia , Doenças Cardiovasculares/tratamento farmacológico , Humanos , Hipertensão/tratamento farmacológico
4.
Open Heart ; 7(2)2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33154144

RESUMO

OBJECTIVE: The association between the use of renin-angiotensin-aldosterone (RAAS) inhibitors and the risk of mortality from COVID-19 is unclear. We aimed to estimate the association of RAAS inhibitors, including ACE inhibitors (ACEi) and angiotensin II receptor blockers (ARBs) with COVID-19 mortality risk in patients with hypertension. METHODS: PubMed (MEDLINE) SCOPUS, OVID, Cochrane Library databases and medrxiv.org were searched from 1 January 2020 to 1 September 2020. Studies reporting the association of RAAS inhibitors (ACEi or ARBs) and mortality in patients with hypertension, hospitalised for COVID-19 were extracted. Two reviewers independently extracted appropriate data of interest and assessed the risk of bias. All analyses were performed using random-effects models on log-transformed risk ratio (RR) estimates, and heterogeneity was quantified. RESULTS: Fourteen studies were included in the systematic review (n=73,073 patients with COVID-19; mean age 61 years; 53% male). Overall, the between-study heterogeneity was high (I2=80%, p<0.01). Patients with hypertension with prior use of RAAS inhibitors were 35% less likely to die from COVID-19 compared with patients with hypertension not taking RAAS inhibitors (pooled RR 0.65, 95% CI 0.45 to 0.94). The quality of evidence by Grading of Recommendations, Assessment, Development and Evaluations was graded as 'moderate' quality. CONCLUSIONS: In this meta-analysis, with prior use of RAAS inhibitors was associated with lower risk mortality from COVID-19 in patients with hypertension. Our findings suggest a potential protective effect of RAAS-inhibitors in COVID-19 patients with hypertension. PROSPERO REGISTRATION NUMBER: The present study has been registered with PROSPERO (registration ID: CRD 42020187963).


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Infecções por Coronavirus/mortalidade , Hospitalização , Hipertensão/tratamento farmacológico , Pneumonia Viral/mortalidade , Sistema Renina-Angiotensina/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/terapia , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/mortalidade , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , Fatores de Proteção , Medição de Risco , Fatores de Risco , Resultado do Tratamento
5.
JAMA ; 324(18): 1884-1895, 2020 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-33170247

RESUMO

Importance: Childhood hypertension can result in adverse outcomes during adulthood; identifying and treating primary and secondary childhood hypertension may reduce such risks. Objective: To update the evidence on screening and treatment of hypertension in childhood and adolescence for the US Preventive Services Task Force. Data Sources: PubMed, Cochrane Library, International Pharmaceutical Abstracts, EMBASE, and trial registries through September 3, 2019; bibliographies from retrieved articles, experts, and surveillance of the literature through October 6, 2020. Study Selection: Fair- or good-quality English-language studies evaluating diagnostic accuracy of blood pressure screening; cohort studies assessing the association of hypertension in childhood and adolescence with blood pressure or other intermediate outcomes in adulthood; randomized clinical trials (RCTs) or meta-analyses of pharmacological and lifestyle interventions. Data Extraction and Synthesis: Two reviewers independently assessed titles/abstracts and full-text articles, extracted data, and assessed study quality; the evidence was synthesized qualitatively. Main Outcomes and Measures: Sensitivity, specificity, and measures of association between childhood and adulthood blood pressure; reduction of childhood blood pressure; adverse effects of treatments. Results: Forty-two studies from 43 publications were included (N>12 400). No studies evaluated the benefits or harms of screening and the effect of treating childhood hypertension on outcomes in adulthood. One study reported a sensitivity of 0.82 and a specificity of 0.70 for 2 office-based blood pressure measurements. Twenty observational studies suggested a significant association between childhood hypertension and abnormal blood pressure in adulthood (odds ratios, 1.1-4.5; risk ratios, 1.45-3.60; hazard ratios, 2.8-3.2). Thirteen placebo-controlled RCTs and 1 meta-analysis assessed reductions in systolic (SBP) and diastolic blood pressure from pharmacological treatments. Pooled reductions of SBP were -4.38 mm Hg (95% CI, -7.27 to -2.16) for angiotensin-converting enzyme inhibitors and -3.07 mm Hg (95% CI, -4.99 to -1.44) for angiotensin receptor blockers. Candesartan reduced SBP by -6.56 mm Hg (P < .001; n = 240). ß-Blockers, calcium channel blockers, and mineralocorticoid receptor antagonists did not achieve significant reductions over 2 to 4 weeks. SBP was significantly reduced by exercise over 8 months (-4.9 mm Hg, P ≤ .05; n = 69), by dietary approaches to stop hypertension over 3 months (-2.2 mm Hg, P < .01; n = 57), and by a combination of drug treatment and lifestyle interventions over 6 months (-7.6 mm Hg; P < .001; n = 95). Low-salt diet did not achieve reductions of blood pressure. Conclusions and Relevance: Observational studies indicate an association between hypertension in childhood and hypertension in adulthood. However, the evidence is inconclusive whether the diagnostic accuracy of blood pressure measurements is adequate for screening asymptomatic children and adolescents in primary care.


Assuntos
Hipertensão/diagnóstico , Programas de Rastreamento , Adolescente , Adulto , Anti-Hipertensivos/efeitos adversos , Anti-Hipertensivos/uso terapêutico , Determinação da Pressão Arterial/instrumentação , Doenças Cardiovasculares/prevenção & controle , Criança , Pré-Escolar , Terapia Combinada , Dieta Saudável , Exercício Físico , Feminino , Humanos , Hipertensão/terapia , Masculino , Programas de Rastreamento/efeitos adversos , Programas de Rastreamento/psicologia , Estudos Observacionais como Assunto , Guias de Prática Clínica como Assunto , Serviços Preventivos de Saúde , Sensibilidade e Especificidade
7.
Orv Hetil ; 161(45): 1908-1913, 2020 11 08.
Artigo em Húngaro | MEDLINE | ID: mdl-33161389

RESUMO

Összefoglaló. Bevezetés: Az atorvasztatin (koleszterincsökkento), nifedipin (Ca2+-antagonista), kaptopril (angiotenzinkonvertáz-gátló) vegyületek a magas vérnyomás komplex kezelésének "alap"gyógyszerei. Mindhárom antioxidáns is. Célkituzés: A tanulmány célja annak megválaszolása volt, hogy e molekulák gátolhatják-e a vérsejtek fagocitamuködését. Betegek és módszer: Magas vérnyomásos betegek: 15 fo, 39-80 éves, no: 6, férfi: 9. Egészséges kontroll: 7 fo, 30-75 éves, no: 3, férfi: 4. A vizsgálat a téli hónapokban zajlott. A zimozán- (Saccharomyces cerevisiae) részecskék fagocitózisa során képzodo kemilumineszcencia mérése perifériás vérben a gyógyszerek jelenlétében történt luminométerrel. A gátlást a stimulációs index értékének csökkenésével jellemeztük. Eredmények: Mindhárom vegyület gátolta a kemilumineszcenciát (oxigénszabadgyök-képzést) a 65 év feletti, magas vérnyomásos betegek többségében: 11/13 fonél. Foleg magasabb életkorban és cukorbetegségben, de más társbetegségekben nott a gátlás. Következtetés: Az idos, magas vérnyomásos betegek fokozott orvosi figyelmet igényelnek a téli idoszakokban, mivel antioxidáns hatással is rendelkezo "alap"gyógyszereiknek, egyéntol függoen, lehetnek gátló hatásaik a fagociták mikrobaölo, oxigénszabadgyök-termelo képességére. Orv Hetil. 2020; 161(45): 1908-1913. INTRODUCTION: Atorvastatin (cholesterol synthesis blocker), nifedipine (Ca2+ antagonist), captopril (angiotensin-convertase inhibitor) are basic drugs in the therapy of hypertension. They are also antioxidants. OBJECTIVE: To investigate whether these molecules can inhibit the phagocytic activity of peripheral blood cells. PATIENTS AND METHOD: Hypertension group: 15 patients with ages between 39-80 years (6 women and 9 men). Healthy control group: 7 individuals with ages between 30-75 years (3 women and 4 men). The study was carried out in wintertime. The measurement of phagocytic activity was carried out by luminometry in peripheral blood samples. Chemiluminescence intensities were determined by the engulfment of zymosan (Saccharomyces cerevisiae) particles in the presence of drugs. The inhibitory effects were characterized by the decreased values of the stimulation index. RESULTS: All three substances decreased the chemiluminescence (reactive oxygen species production) in the majority of samples from hypertensive patients over 65 years: in 11 of 13 patients. Stronger inhibition was detected in older, diabetic patients with other co-morbidities, too. CONCLUSION: Older patients with hypertension require a special attention in wintertime. Antihypertensive drugs with antioxidant capabilities may have individually different inhibitory effects on the production of reactive oxygen species by phagocytes, which decreases their antimicrobial potency. Orv Hetil. 2020; 161(45): 1908-1913.


Assuntos
Antioxidantes , Hipertensão , Fagócitos , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/farmacologia , Antioxidantes/farmacologia , Feminino , Humanos , Hipertensão/tratamento farmacológico , Luminescência , Masculino , Pessoa de Meia-Idade , Fagócitos/efeitos dos fármacos
8.
High Blood Press Cardiovasc Prev ; 27(6): 587-596, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33165768

RESUMO

INTRODUCTION: Despite hypertension guidelines suggest that the most effective treatment strategy to improve blood pressure (BP) target achievement is to implement the use of combination treatment, monotherapy is still widely used in the clinical practice of hypertension. AIM: To investigate BP control under monotherapy in the setting of real-life. METHODS: We extracted data from a medical database of adult outpatients who were referred to the Hypertension Unit, Sant'Andrea Hospital, Rome (IT), including anthropometric data, CV risk factors and comorbidities, presence or absence of antihypertensive therapy and concomitant medications. Among treated hypertensive patients, we identified only those under single antihypertensive agent (monotherapy). Office BP treatment targets were defined according to 2018 ESC/ESH guidelines as: (a) < 130/80 mmHg in individuals aged 18-65 years; (b) < 140/80 mmHg in those aged > 65 years. RESULTS: From an overall sample of 7797 records we selected 1578 (20.2%) hypertensive outpatients (47.3% female, age 59.5 ± 13.6 years, BMI 26.6 ± 4.4 kg/m2) treated with monotherapies, among whom 30.5% received ACE inhibitors, 37.7% ARBs, 15.8% beta-blockers, 10.6% CCBs, 3.0% diuretics, and 2.0% alpha-blockers. 36.6% of these patients reached the conventional clinic BP goal of < 140/90 mmHg, whilst the 2018 European guidelines BP treatment targets were fulfilled only in 14.0%. In particular, 10.2% patients aged 18-65 years and 20.4% of those aged > 65 years achieved the recommended BP goals. All these proportions results significantly lower than those achieved with dual (18.2%) or triple (22.2%) combination therapy, though higher than those obtained with life-style changes (10.8%). Proportions of patients on monotherapies with normal home and 24-h BP levels were 22.0% and 30.2%, respectively, though only 5.2% and 7.3% of these patients achieved sustained BP control, respectively. Ageing and dyslipidaemia showed significant and independent positive predictive value for the achievement of the recommended BP treatment targets, whereas European SCORE resulted a negative and independent predictor in outpatients treated with monotherapies. CONCLUSIONS: Our data showed a persistent use of monotherapy in the clinical practice, though with unsatisfactory BP control, especially in light of the BP treatment targets suggested by the last hypertension guidelines.


Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Adolescente , Adulto , Idoso , Anti-Hipertensivos/efeitos adversos , Estudos Transversais , Bases de Dados Factuais , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Roma , Resultado do Tratamento , Adulto Jovem
9.
Methodist Debakey Cardiovasc J ; 16(3): 241-244, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33133361

RESUMO

BRASH syndrome is characterized by bradycardia, renal failure, use of an atrioventricular nodal blocker (AVNB), shock, and hyperkalemia. These symptoms represent an ongoing vicious cycle in a patient with a low glomerular filtration rate taking an AVNB. Decreased clearance of the medication and hyperkalemia associated with renal failure synergize to cause bradycardia and hypoperfusion. This reaction causes renal function to worsen, thereby perpetuating the cycle of BRASH syndrome.


Assuntos
Anti-Hipertensivos/efeitos adversos , Nó Atrioventricular/efeitos dos fármacos , Bradicardia/induzido quimicamente , Diltiazem/efeitos adversos , Hiperpotassemia/etiologia , Insuficiência Renal Crônica/complicações , Nó Atrioventricular/fisiopatologia , Bradicardia/diagnóstico , Bradicardia/fisiopatologia , Bradicardia/terapia , Feminino , Taxa de Filtração Glomerular , Humanos , Hiperpotassemia/diagnóstico , Hiperpotassemia/fisiopatologia , Hiperpotassemia/terapia , Rim/fisiopatologia , Pessoa de Meia-Idade , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/terapia , Síndrome , Resultado do Tratamento
10.
Kardiologiia ; 60(10): 132-140, 2020 Nov 12.
Artigo em Russo | MEDLINE | ID: mdl-33228516

RESUMO

Arterial hypertension (AH) and exertional headache (EHA) are comorbidities. The article presents a nonsystematic review focused on studying the AH+EHA phenotype. The authors addressed the history of studying the phenotype, several theories about its pathophysiological causes (psychosomatic, neuroanatomical, and baroreflector). The protective "hypertension-associated hypoalgesia" phenotype, a mechanism of its change in AH chronization, and difficulties of differential diagnosis are described. The AH+EHA phenotype requires further study since its incidence is quite high. This will allow developing an individualized approach in prevention and treatment of EHA attacks, decreasing the risk of life-threatening cardiovascular complications, and avoiding iatrogenic complications in patients with AH. The main way to prevent the development of AH+EHA phenotype is patient's compliance, which can be provided by using combination hypotensive drugs to reduce the number of pills and dosing. It is important to take into account possible adverse reactions of the nervous system (medication-overuse headache or EHA aggravation). Considering these conditions, the drug Triplixam can be used for prevention of complications in the AH+EHA phenotype. Triplixam is a fixed triple combination of amlodipine/indapamide/perindopril, and its individual components have low and medium risk for development of headache.


Assuntos
Hipertensão , Indapamida , Cefaleia do Tipo Tensional , Anlodipino/farmacologia , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , Comorbidade , Combinação de Medicamentos , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Perindopril/farmacologia , Cefaleia do Tipo Tensional/tratamento farmacológico , Cefaleia do Tipo Tensional/epidemiologia
11.
Medicine (Baltimore) ; 99(40): e22310, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019406

RESUMO

Immunoglobulin A nephropathy (IgAN) is a major cause of secondary hypertension (HT) of renal origin - a significant prognostic factor of IgAN. In children, similar to HT, prehypertension (pre-HT) is becoming a significant health issue. However, the role of secondary HT and pre-HT (HT/pre-HT) in the progression of pediatric IgAN remains unclear. We investigated the effects of HT/pre-HT on prognosis and its determinants as well as their correlation with clinicopathological parameters to identify more effective therapeutic targets.This single-center retrospective study compared clinicopathological features and treatment outcomes between patients with and without HT/pre-HT in 108 children with IgAN. Independent risk factors for HT/pre-HT were evaluated; segmental glomerulosclerosis was a significant variable, whose relationship with clinicopathological parameters was analyzed.Clinical outcomes of patients with and without HT/pre-HT differed considerably (P = .006) on ≥6 months follow-up. Patients with HT/pre-HT reached complete remission less frequently than those without HT/pre-HT (P = .014). Age, serum creatinine, prothrombin time, and segmental glomerulosclerosis or adhesion were independent risk factors for HT/pre-HT in pediatric IgAN (P = .012, P = .017, P = .002, and P = .016, respectively). Segmental glomerulosclerosis or adhesion was most closely associated with glomerular crescents (r = 0.456, P < .01), followed by Lees grades (r = 0.454, P < .01), renal arteriolar wall thickening (r = 0.337, P < .01), and endocapillary hypercellularity (r = 0.306, P = .001). The intensity of IgA deposits, an important marker of pathogenetic activity in IgAN, was significantly associated with the intensity and location of fibrinogen deposits (intensity: r = 0.291, P = .002; location: r = 0.275, P = .004).HT/pre-HT in pediatric IgAN patients is an important modifiable factor. A relationship is observed between HT/pre-HT and its determinants, especially segmental glomerulosclerosis. Potential therapeutic approaches for IgAN with HT/pre-HT might be directed toward the management of coagulation status, active lesions, and hemodynamics for slowing disease progression.


Assuntos
Glomerulonefrite por IGA/epidemiologia , Hipertensão/epidemiologia , Pré-Hipertensão/epidemiologia , Adolescente , Fatores Etários , Anti-Hipertensivos/uso terapêutico , Biomarcadores , Criança , Creatinina/sangue , Progressão da Doença , Feminino , Fibrinolíticos/uso terapêutico , Taxa de Filtração Glomerular , Glomerulonefrite por IGA/tratamento farmacológico , Glomerulosclerose Segmentar e Focal/epidemiologia , Humanos , Hipertensão/tratamento farmacológico , Imunossupressores/uso terapêutico , Masculino , Pré-Hipertensão/tratamento farmacológico , Prognóstico , Tempo de Protrombina , Estudos Retrospectivos , Fatores de Risco
15.
Trials ; 21(1): 846, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33050924

RESUMO

OBJECTIVES: To assess the efficacy of several repurposed drugs to prevent hospitalisation or death in patients aged 65 or more with recent symptomatic SARS-CoV-2 infection (COVID-19) and no criteria for hospitalisation. TRIAL DESIGN: Phase III, multi-arm (5) and multi-stage (MAMS), randomized, open-label controlled superiority trial. Participants will be randomly allocated 1:1:1:1:1 to the following strategies: Arm 1: Control arm Arms 2 to 5: Experimental treatment arms Planned interim analyses will be conducted at regular intervals. Their results will be reviewed by an Independent Data and Safety Monitoring Board. Experimental arms may be terminated for futility, efficacy or toxicity before the end of the trial. New experimental arms may be added if new evidence suggests that other treatments should be tested. A feasibility and acceptability substudy as well as an immunological substudy will be conducted alongside the trial. PARTICIPANTS: Inclusion criteria are: 65-year-old or more; Positive test for SARS-CoV-2 on a nasopharyngeal swab; Symptoms onset within 3 days before diagnosis; No hospitalisation criteria; Signed informed consent; Health insurance. Exclusion criteria are: Inability to make an informed decision to participate (e.g.: dementia, guardianship); Rockwood Clinical Frailty Scale ≥7; Long QT syndrome; QTc interval > 500 ms; Heart rate <50/min; Kalaemia >5.5 mmol/L or <3.5 mmol/L; Ongoing treatment with piperaquine, halofantrine, dasatinib, nilotinib, hydroxyzine, domperidone, citalopram, escitalopram, potent inhibitors or inducers of cytochrome P450 CYP3A4 isoenzyme, repaglinide, azathioprine, 6-mercaptopurine, theophylline, pyrazinamide, warfarin; Known hypersensitivity to any of the trial drugs or to chloroquine and other 4-aminoquinolines, amodiaquine, mefloquine, glafenine, floctafenine, antrafenine, ARB; Hepatic porphyria; Liver failure (Child-Pugh stage ≥B); Stage 4 or 5 chronic kidney disease (GFR <30 mL/min/1.73 m²); Dialysis; Hypersentivity to lactose; Lactase deficiency; Abnormalities in galactose metabolism; Malabsorption syndrome; Glucose-6-phosphate dehydrogenase deficiency; Symptomatic hyperuricemia; Ileus; Colitis; Enterocolitis; Chronic hepatitis B virus disease. The trial is being conducted in France in the Bordeaux, Corse, Dijon, Nancy, Paris and Toulouse areas as well as in the Grand Duchy of Luxembourg. Participants are recruited either at home, nursing homes, general practices, primary care centres or hospital outpatient consultations. INTERVENTION AND COMPARATOR: The four experimental treatments planned in protocol version 1.2 (April 8th, 2020) are: (1) Hydroxychloroquine 200 mg, 2 tablets BID on day 0, 2 tablets QD from day 1 to 9; (2) Imatinib 400 mg, 1 tablet QD from day 0 to 9; (3) Favipiravir 200 mg, 12 tablets BID on day 0, 6 tablets BID from day 1 to 9; (4) Telmisartan 20 mg, 1 tablet QD from day 0 to 9. The comparator is a complex of vitamins and trace elements (AZINC Forme et Vitalité®), 1 capsule BID for 10 days, for which there is no reason to believe that they are active on the virus. In protocol version 1.2 (April 8th, 2020): People in the control arm will receive a combination of vitamins and trace elements; people in the experimental arms will receive hydroxychloroquine, or favipiravir, or imatinib, or telmisartan. MAIN OUTCOME: The primary outcome is the proportion of participants with an incidence of hospitalisation and/or death between inclusion and day 14 in each arm. RANDOMISATION: Participants are randomized in a 1:1:1:1:1 ratio to each arm using a web-based randomisation tool. Participants not treated with an ARB or ACEI prior to enrolment are randomized to receive the comparator or one of the four experimental drugs. Participants already treated with an ARB or ACEI are randomized to receive the comparator or one of the experimental drugs except telmisartan (i.e.: hydroxychloroquine, imatinib, or favipiravir). Randomisation is stratified on ACEI or ARBs treatment at inclusion and on the type of residence (personal home vs. nursing home). BLINDING (MASKING): This is an open-label trial. Participants, caregivers, investigators and statisticians are not blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 1057 participants will be enrolled if all arms are maintained until the final analysis and no additional arm is added. Three successive futility interim analyses are planned, when the number of participants reaches 30, 60 and 102 in the control arm. Two efficacy analyses (interim n°3 and final) will be performed successively. TRIAL STATUS: This describes the Version 1.2 (April 8th, 2020) of the COVERAGE protocol that was approved by the French regulatory authority and ethics committee. The trial was opened for enrolment on April 15th, 2020 in the Nouvelle Aquitaine region (South-West France). Given the current decline of the COVID-19 pandemic in France and its unforeseeable dynamic in the coming months, new trial sites in 5 other French regions and in Luxembourg are currently being opened. A revised version of the protocol was submitted to the regulatory authority and ethics committee on June 15th, 2020. It contains the following amendments: (i) Inclusion criteria: age ≥65 replaced by age ≥60; time since first symptoms <3 days replaced by time since first symptoms <5 days; (ii) Withdrawal of the hydroxychloroquine arm (due to external data); (iii) increase in the number of trial sites. TRIAL REGISTRATION: The trial was registered on Clinical Trials.gov on April 22nd, 2020 (Identifier: NCT04356495): and on EudraCT on April 10th, 2020 (Identifier: 2020-001435-27). FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/tratamento farmacológico , Pacientes Ambulatoriais/estatística & dados numéricos , Pneumonia Viral/tratamento farmacológico , Terapias em Estudo/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Amidas/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Antimaláricos/uso terapêutico , Antivirais/uso terapêutico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Tolerância a Medicamentos , Estudos de Viabilidade , França/epidemiologia , Hospitalização/tendências , Humanos , Hidroxicloroquina/uso terapêutico , Mesilato de Imatinib/uso terapêutico , Luxemburgo/epidemiologia , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Inibidores de Proteínas Quinases/uso terapêutico , Pirazinas/uso terapêutico , Comportamento de Redução do Risco , Telmisartan/uso terapêutico , Resultado do Tratamento
16.
Artigo em Inglês | MEDLINE | ID: mdl-33093771

RESUMO

Background: Pulmonary hypertension (PH) is a known complication of pulmonary sarcoidosis and is associated with higher morbidity and mortality. Currently, there are no approved PH-targeted therapies for sarcoidosis-associated pulmonary hypertension (SAPH). Macitentan is frequently used as treatment for pulmonary arterial hypertension, but no results are known in the SAPH population. Objective: We investigated the safety and effect of macitentan as treatment for SAPH. Methods: We retrospectively reviewed our patient database for all SAPH patients receiving macitentan as treatment, with a minimum follow-up of twelve months for monitoring safety. Safety outcomes included reported side-effects, hospitalisations and mortality. Furthermore, six-minutes walking distance, New York Heart Association functional class and NT-proBNP levels were collected. Results: Six cases (three men) with a median age of 64 years (range 52-74 years) were identified. During macitentan treatment, one patient experienced side effects and aborted therapy after five days of treatment and died 16 months later. Three patients were hospitalised during treatment for congestive heart failure. Four patients showed improvement of their functional class and three patients in exercise capacity after 12 months of therapy. Conclusion: Macitentan was well tolerated in five out of six cases with severe pulmonary sarcoidosis and PH. Functional capacity improved in four cases. Prospective controlled trials are warranted before therapeutic recommendations can be made. (Sarcoidosis Vasc Diffuse Lung Dis 2020; 37 (1): 74-78).


Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Arterial/efeitos dos fármacos , Antagonistas dos Receptores de Endotelina/uso terapêutico , Hipertensão Pulmonar/tratamento farmacológico , Artéria Pulmonar/efeitos dos fármacos , Pirimidinas/uso terapêutico , Sarcoidose Pulmonar/complicações , Sulfonamidas/uso terapêutico , Idoso , Anti-Hipertensivos/efeitos adversos , Bases de Dados Factuais , Antagonistas dos Receptores de Endotelina/efeitos adversos , Tolerância ao Exercício/efeitos dos fármacos , Feminino , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/fisiopatologia , Masculino , Pessoa de Meia-Idade , Artéria Pulmonar/fisiopatologia , Recuperação de Função Fisiológica , Estudos Retrospectivos , Sarcoidose Pulmonar/diagnóstico , Fatores de Tempo , Resultado do Tratamento
17.
Sarcoidosis Vasc Diffuse Lung Dis ; 37(2): 184-191, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33093782

RESUMO

Sarcoidosis-Associated Pulmonary Hypertension (SAPH) is a common finding in patients with chronic sarcoidosis and is associated with increased mortality. The optimal treatment for SAPH is not known; however, therapies approved for Group 1 pulmonary hypertension have improved hemodynamics and functional status. Prostanoids, including epoprostenol, have been therapeutic in short-term studies of SAPH, but long-term efficacy is unknown. In this study, we evaluated the long-term effect of epoprostenol therapy in 12 patients with SAPH. Hemodynamic assessment after an average of 4.1 years of epoprostenol therapy demonstrated significant improvement in mean pulmonary arterial pressure, pulmonary vascular resistance, and cardiac output; furthermore, patients demonstrated improved NYHA functional class. To evaluate further the long-term effect of epoprostenol, we compared survival of SAPH patients to a cohort of hemodynamically matched patients from the same center treated with epoprostenol for Idiopathic Pulmonary Arterial Hypertension (IPAH). Interestingly, there was no difference in survival, despite the additional systemic disease burden of the SAPH subjects. Subgroup analysis by Scadding stage demonstrated that Scadding stages 1-3 had improved survival compared to Scadding stage 4. These observations suggest that epoprostenol is an effective long-term therapy for patients with SAPH; it improves hemodynamics, functional class, and provides survival similar to that seen in a hemodynamically-matched cohort of IPAH patients. Furthermore, we identify a subgroup of SAPH patients (nonfibrotic lung disease Scadding 1-3) who may derive significant benefit from prostanoid therapy. (Sarcoidosis Vasc Diffuse Lung Dis 2020; 37 (2): 184-191).


Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Arterial/efeitos dos fármacos , Epoprostenol/uso terapêutico , Hipertensão Pulmonar/tratamento farmacológico , Artéria Pulmonar/efeitos dos fármacos , Sarcoidose/complicações , Adulto , Anti-Hipertensivos/efeitos adversos , Débito Cardíaco/efeitos dos fármacos , Doença Crônica , Epoprostenol/efeitos adversos , Feminino , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/fisiopatologia , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Artéria Pulmonar/fisiopatologia , Estudos Retrospectivos , Sarcoidose/diagnóstico , Sarcoidose/tratamento farmacológico , Fatores de Tempo , Resultado do Tratamento , Resistência Vascular/efeitos dos fármacos
18.
Sarcoidosis Vasc Diffuse Lung Dis ; 37(2): 234-238, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33093789

RESUMO

Sarcoid Associated Pulmonary Hypertension (SAPH) is a common complication of sarcoidosis and is associated with poor prognosis. SAPH can be due to multiple synergistic mechanisms and current therapeutic strategies treat systemic sarcoidosis and pulmonary hypertension separately. Several studies have been performed to develop an effective therapy for SAPH but have been met with mixed results. The AMBITION trial successfully treated incident patients with pulmonary arterial hypertension (PAH) with the upfront combination of ambrisentan and tadalafil; however combination therapy has not yet been studied in patients with SAPH. Here we report a cohort of patients with newly diagnosed SAPH who were treated with upfront combination therapy per the AMBITION study protocol. We report three subjects with newly diagnosed SAPH who were treated with combination ambrisentan and tadalafil. Baseline hemodynamics were compared with those from surveillance right heart catheterization while on therapy. Mean follow up period was 17 months. Each subject demonstrated clinical and hemodynamic improvement with combination therapy. This series is the first to evaluate upfront combination ambrisentan and tadalafil therapy for treatment of newly diagnosed SAPH. Despite the impressive clinical and hemodynamic improvement, the study is limited by its small size and retrospective nature. While these initial results are promising, further work is needed to fully evaluate this regimen for treatment of SAPH. (Sarcoidosis Vasc Diffuse Lung Dis 2020; 37 (2): 234-238).


Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Arterial/efeitos dos fármacos , Antagonistas do Receptor de Endotelina A/uso terapêutico , Hipertensão Pulmonar/tratamento farmacológico , Fenilpropionatos/uso terapêutico , Inibidores da Fosfodiesterase 5/uso terapêutico , Artéria Pulmonar/efeitos dos fármacos , Piridazinas/uso terapêutico , Sarcoidose Pulmonar/complicações , Tadalafila/uso terapêutico , Adulto , Idoso , Quimioterapia Combinada , Feminino , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/fisiopatologia , Transplante de Pulmão , Masculino , Pessoa de Meia-Idade , Artéria Pulmonar/fisiopatologia , Estudos Retrospectivos , Sarcoidose Pulmonar/diagnóstico , Resultado do Tratamento
19.
Lancet Neurol ; 19(11): 899-907, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33098800

RESUMO

BACKGROUND: Results from the Systolic Blood Pressure Intervention Trial (SPRINT) showed that intensive control of systolic blood pressure significantly reduced the occurrence of mild cognitive impairment, but not probable dementia. We investigated the effects of intensive lowering of systolic blood pressure on specific cognitive functions in a preplanned substudy of participants from SPRINT. METHODS: SPRINT was an open-label, multicentre, randomised controlled trial undertaken at 102 sites, including academic medical centres, Veterans Affairs medical centres, hospitals, and independent clinics, in the USA and Puerto Rico. Participants were adults aged 50 years or older with systolic blood pressure higher than 130 mm Hg, but without diabetes, history of stroke, or dementia. Participants were randomly assigned (1:1) to a systolic blood pressure goal of less than 120 mm Hg (intensive treatment) versus less than 140 mm Hg (standard treatment). All major classes of antihypertensive agents were included. A subgroup of randomly assigned participants including, but not limited to, participants enrolled in an MRI substudy was then selected for a concurrent substudy of cognitive function (target 2800 participants). Each individual was assessed with a screening cognitive test battery and an extended cognitive test battery at baseline and biennially during the planned 4-year follow-up. The primary outcomes for this substudy were standardised composite scores for memory (Logical Memory I and II, Modified Rey-Osterrieth Complex Figure [immediate recall], and Hopkins Verbal Learning Test-Revised [delayed recall]) and processing speed (Trail Making Test and Digit Symbol Coding). SPRINT was registered with ClinicalTrials.gov, NCT01206062. FINDINGS: From Nov 23, 2010, to Dec 28, 2012, 2921 participants (mean age 68·4 years [SD 8·6], 1080 [37%] women) who had been randomly assigned in SPRINT were enrolled in the substudy (1448 received intensive treatment and 1473 received standard treatment). SPRINT was terminated early due to benefit observed in the primary outcome (composite of cardiovascular events). After a median follow-up of 4·1 years (IQR 3·7-5·8), there was no between-group difference in memory, with an annual decline in mean standardised domain score of -0·005 (95% CI -0·010 to 0·001) in the intensive treatment group and -0·001 (-0·006 to 0·005) in the standard treatment group (between-group difference -0·004, 95% CI -0·012 to 0·004; p=0·33). Mean standardised processing speed domain scores declined more in the intensive treatment group (between-group difference -0·010, 95% CI -0·017 to -0·002; p=0·02), with an annual decline of -0·025 (-0·030 to -0·019) for the intensive treatment group and -0·015 (-0·021 to 0·009) for the standard treatment group. INTERPRETATION: Intensive treatment to lower systolic blood pressure did not result in a clinically relevant difference compared with standard treatment in memory or processing speed in a subgroup of participants from SPRINT. The effect of blood pressure lowering might not be evident in specific domains of cognitive function, but instead distributed across multiple domains. FUNDING: National Heart, Lung, and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute on Aging, National Institute of Neurological Disorders and Stroke, and the Alzheimer's Association.


Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Cognição/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Testes de Estado Mental e Demência , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/farmacologia , Pressão Sanguínea/fisiologia , Monitorização Ambulatorial da Pressão Arterial/métodos , Monitorização Ambulatorial da Pressão Arterial/tendências , Cognição/fisiologia , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/prevenção & controle , Disfunção Cognitiva/psicologia , Feminino , Seguimentos , Humanos , Hipertensão/psicologia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Estados Unidos/epidemiologia , United States Department of Veterans Affairs/tendências
20.
Medicine (Baltimore) ; 99(43): e22920, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33120844

RESUMO

RATIONALE: Reversible splenial lesion syndrome (RESLES) is a recently identified clinico-radiological syndrome, the etiology is miscellaneous. Atrial septal defect (ASD) as an underlying etiology for RESLES has not been reported. We first report a rare case of RESLES associated with ASD. The clinical, radiological, and ultrasonic profiles were presented and the pathophysiological mechanism was analyzed. PATIENT CONCERNS: A 23-year-old man presented with headache, drowsiness, occasional paraphasia, and paroxysmal dry cough. Brain magnetic resonance imaging (MRI) on admission showed an ovoid isolated lesion in the splenium of corpus callosum, which exhibited hyperintensity on diffusion-weighted imaging and hypointensity on apparent diffusion coefficient, and completely disappeared on the follow-up MRI 14 days later. ASD was found by transthoracic echocardiography, Right-to-left shunts were detected on color Doppler of transesophageal echocardiography, and microemboli were captured by transcranial Doppler ultrasound. DIAGNOSES: According to his clinical history and imaging results, we confirmed the diagnosis of RESLES associated with ASD. INTERVENTIONS: The patient was treated by oral aspirin and lopidogrel sulfate to inhibit platelet aggregation. In addition, oral nimodipine to suppress vasoconstriction. OUTCOMES: After 14 days treatment, all the symptoms presenting on admission resolved completely. Subsequently, a repair surgery of ASD under thoracoscopy was successfully performed. LESSONS: To our knowledge, this is the first reported case of ASD may be an underlying etiology for RESLES and need require an etiotropic treatment.


Assuntos
Encefalopatias/etiologia , Corpo Caloso/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética/métodos , Comunicação Interatrial/complicações , Administração Oral , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/uso terapêutico , Aspirina/administração & dosagem , Aspirina/uso terapêutico , Encefalopatias/diagnóstico por imagem , Encefalopatias/patologia , Corpo Caloso/patologia , Combinação de Medicamentos , Quimioterapia Combinada , Ecocardiografia/métodos , Seguimentos , Cefaleia/etiologia , Comunicação Interatrial/diagnóstico por imagem , Comunicação Interatrial/tratamento farmacológico , Comunicação Interatrial/cirurgia , Humanos , Lopinavir/administração & dosagem , Lopinavir/uso terapêutico , Masculino , Nimodipina/administração & dosagem , Nimodipina/uso terapêutico , Inibidores da Agregação de Plaquetas/administração & dosagem , Inibidores da Agregação de Plaquetas/uso terapêutico , Ritonavir/administração & dosagem , Ritonavir/uso terapêutico , Síndrome , Resultado do Tratamento , Ultrassonografia Doppler Transcraniana/métodos , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA