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1.
Biomed Pharmacother ; 168: 115661, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37832406

RESUMO

The non-steroidal mineralocorticoid receptor antagonist (MRA) finerenone (FIN) improves kidney and cardiovascular outcomes in patients with chronic kidney disease (CKD) in type 2 diabetes (T2D). We explored the effect of FIN in a novel model of type 1 diabetic Munich Wistar Frömter (MWF) rat (D) induced by injection of streptozotocin (15 mg/kg) and additional exposure to a high-fat/high-sucrose diet. Oral treatment with FIN (10 mg/kg/day in rat chow) in diabetic animals (D-FIN) was compared to a group of D rats receiving no treatment and a group of non-diabetic untreated MWF rats (C) (n = 7-10 animals per group). After 6 weeks, D and D-FIN exhibited significantly elevated blood glucose levels (271.7 ± 67.1 mg/dl and 266.3 ± 46.8 mg/dl) as compared to C (110.3 ± 4.4 mg/dl; p < 0.05). D showed a 10-fold increase of kidney damage markers Kim-1 and Ngal which was significantly suppressed in D-FIN. Blood pressure, pulse wave velocity (PWV) and arterial collagen deposition were lower in D-FIN, associated to an improvement in endothelial function due to a reduction in pro-contractile prostaglandins, as well as reactive oxygen species (ROS) and inflammatory cytokines (IL-1, IL-6, TNFα and TGFß) in perivascular and perirenal adipose tissue (PVAT and PRAT, respectively). In addition, FIN restored the imbalance observed in CKD between the procalcifying BMP-2 and the nephroprotective BMP-7 in plasma, kidney, PVAT, and PRAT. Our data show that treatment with FIN improves kidney and vascular damage in a new rat model of DKD with T1D associated with a reduction in inflammation, fibrosis and osteogenic factors independently from changes in glucose homeostasis.


Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Insuficiência Renal Crônica , Humanos , Ratos , Animais , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Análise de Onda de Pulso , Ratos Wistar , Rim
2.
J Intern Med ; 294(3): 251-268, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37401044

RESUMO

The clinical and economic burden of hypertension is high and continues to increase globally. Uncontrolled hypertension has severe but avoidable long-term consequences, including cardiovascular diseases, which are among the most burdensome and most preventable conditions in Europe. Yet, despite clear guidelines on screening, diagnosis and management of hypertension, a large proportion of patients remain undiagnosed or undertreated. Low adherence and persistence are common, exacerbating the issue of poor blood pressure (BP) control. Although current guidelines provide clear direction, implementation is hampered by barriers at the patient-, physician- and healthcare system levels. Underestimation of the impact of uncontrolled hypertension and limited health literacy lead to low adherence and persistence among patients, treatment inertia among physicians and a lack of decisive healthcare system action. Many options to improve BP control are available or under investigation. Patients would benefit from targeted health education, improved BP measurement, individualized treatment or simplified treatment regimens through single-pill combinations. For physicians, increasing awareness of the burden of hypertension, as well as offering training on monitoring and optimal management and provision of the necessary time to collaboratively engage with patients would be useful. Healthcare systems should establish nationwide strategies for hypertension screening and management. Furthermore, there is an unmet need to implement more comprehensive BP measurements to optimize management. In conclusion, an integrative, patient-focused, multimodal multidisciplinary approach to the management of hypertension by clinicians, payers and policymakers, involving patients, is required to achieve long-term improvements in population health and cost-efficiency for healthcare systems.


Assuntos
Anti-Hipertensivos , Hipertensão , Humanos , Pressão Sanguínea , Anti-Hipertensivos/uso terapêutico , Estresse Financeiro , Hipertensão/diagnóstico , Hipertensão/prevenção & controle , Quimioterapia Combinada
3.
Schmerz ; 35(5): 322-332, 2021 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-33580415

RESUMO

BACKGROUND: Pain prevalence rates of up to 53% are found among older home-care recipients (aged ≥ 60 years). Of people affected by pain in Germany, care recipients comprise a relevant group with prevalence rates of around 70%. The available information on gender-specific pain experience shows a range of differing findings. OBJECTIVE: Our objective was to determine pain parameters of older care receivers in the big city environment who are capable of self-reporting, taking into account gender differences and relevant aspects of medical care and medication. MATERIAL AND METHODS: A cross-sectional study (structured interviews) was carried out among older (≥65 years) home-care recipients (German Social Security Code SGB XI) in Berlin, with chronic pain (n = 225), capable of self-reporting (MMST ≥ 18). Pain parameters were determined using the German version of the brief pain inventory (BPI-NHR). Multiple regression analysis was applied to test and explain how the severest pain was influenced by sociodemographic and medical parameters, mental and physical restrictions, and analgesic provision. RESULTS: Analyses showed an average pain intensity of 5.3 (SD ± 2.0). The severest pain averaged 7.0 (SD ± 2.2). Few indications of significant gender-based differences were found (e.g. pain location, number of medications). The final model identified the number of pain locations (≥14), everyday abilities, and pain medication (as needed, none) as being associated with the severest pain. Treatment achieved pain relief of over 70% in only 24.6% of cases among pain-affected care receivers. CONCLUSION: The findings indicate a significant level of pain experienced by older home-care recipients. Interdisciplinary care concepts are urgently needed.


Assuntos
Dor Crônica , Serviços de Assistência Domiciliar , Dor Crônica/terapia , Estudos Transversais , Alemanha , Humanos , Medição da Dor
5.
Internist (Berl) ; 60(4): 424-430, 2019 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-30770942

RESUMO

Arterial hypertension represents one of the most frequent chronic diseases that can lead to complications, such as stroke, dementia, heart attack, heart failure and renal failure. By 2025 the number of hypertensive patients will increase to approximately 1.6 billion people worldwide. The new guidelines of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH) on the management of arterial hypertension replace the guidelines of the ESC/ESH from 2013. The 2018 guidelines of the ESC/ESH were adopted by the German Cardiac Society and the German Hypertension League. In these comments national characteristics are worked out and the essential new aspects of the guidelines are critically discussed. These include, for example, the definition of hypertension, the importance of out of office blood pressure measurements, revised blood pressure targets, the modified algorithm for drug treatment and the relevance of device-based hypertension treatments. Important aspects for the management of hypertensive emergencies are also presented.


Assuntos
Cardiologia , Hipertensão , Anti-Hipertensivos , Pressão Sanguínea , Determinação da Pressão Arterial , Humanos
6.
Schmerz ; 33(2): 165-179, 2019 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-30535850

RESUMO

Due to high prescription rates as well as the frequent use as over the counter drugs, it is of interest to consider non-opioid analgesics when evaluating the quality and appropriateness of a given overall medication. This article sums up the basic pharmacology and main adverse effects of these analgesics. Non-opioids can be further classified according to their additional mechanisms of action besides analgesia. High-dose acetylsalicylic acid, traditional nonsteroidal anti-inflammatory drugs, and coxibs exhibit antipyretic and anti-inflammatory properties. Acetaminophen and metamizole (dipyrone) are analgesics and antipyretic agents, while metamizole exhibits also spasmolytic effects. Capsaicin and intrathecal ziconotide are pure analgesics.


Assuntos
Analgésicos não Narcóticos , Acetaminofen , Anti-Inflamatórios não Esteroides , Dipirona
7.
Herz ; 43(4): 352-358, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28534177

RESUMO

BACKGROUND: In the 2013 European Society of Hypertension (ESH) and European Society of Cardiology (ESC) guidelines for the management of arterial hypertension, six lifestyle changes for treatment are recommended for the first time with class I, level of evidence A. We initiated a survey among physicians to explore their awareness and consideration of lifestyle changes in hypertension management. METHODS: The survey included questions regarding demographics as well as awareness and implementation of the recommended lifestyle changes. It was conducted at two German and two European scientific meetings in 2015. RESULTS: In all, 1064 (37.4% female) physicians participated (806 at the European and 258 at the German meetings). Of the six recommended lifestyle changes, self-reported awareness was highest for regular exercise (85.8%) followed by reduction of weight (66.2%). The least frequently self-reported lifestyle changes were the advice to quit smoking (47.3%) and moderation of alcohol consumption (36.3%). Similar frequencies were observed for the lifestyle changes implemented by physicians in their care of patients. CONCLUSION: A close correlation between awareness of guideline recommendations and their implementation into clinical management was observed. European physicians place a stronger emphasis on regular exercise and weight reduction than on the other recommended lifestyle changes. Moderation of alcohol consumption is the least emphasized lifestyle change.


Assuntos
Exercício Físico , Hipertensão , Estilo de Vida , Adulto , Idoso , Cardiologia , Feminino , Humanos , Hipertensão/terapia , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Adulto Jovem
8.
Pharmacogenomics J ; 18(2): 227-231, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28418009

RESUMO

The genetic rs12917707-G>T variant in uromodulin (UMOD) has been associated with renal function, chronic kidney disease and hypertension with the minor T-allele showing a protective effect. Hypertension and nephrotoxicity are adverse effects of chronic cyclosporine treatment. We tested whether UMOD rs12917707-T in donor kidneys associates with long-term graft survival in 393 Caucasian patients with stable graft function for more than 10 weeks after kidney transplantation treated with a cyclosporine-based maintenance therapy (mean graft survival 9 years). Presence of the donor T-allele had no effect on blood pressure, serum creatinine 1 year after transplantation, and on number of acute graft rejections during the first year. No significant effect on overall graft survival was observed in Kaplan-Meier analysis (P=0.65). In death-censored adjusted multivariate analysis, presence of donor T-allele associated with a significant lower hazard ratio of 0.67 (95% confidence interval: 0.46-0.97, P=0.05) for graft loss. This protective effect of the donor T-allele on graft loss observed in multivariate adjusted analysis justifies further investigations including patients treated with similar or other immunosuppressive regimens.


Assuntos
Ciclosporina/farmacologia , Genótipo , Sobrevivência de Enxerto/genética , Imunossupressores/farmacologia , Transplante de Rim/tendências , Uromodulina/genética , Adulto , Feminino , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Fatores de Tempo , Doadores de Tecidos , Resultado do Tratamento
9.
J Thromb Haemost ; 15(10): 2017-2028, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28805299

RESUMO

Essentials In this crossover study the anticoagulant effects of rivaroxaban and apixaban were compared. Healthy volunteers received rivaroxaban 20 mg once daily or apixaban 5 mg twice daily. Rivaroxaban was associated with more prolonged inhibition of thrombin generation than apixaban. Rivaroxaban induced a clear prolongation of prothrombin time and activated partial thromboplastin time. SUMMARY: Background The anticoagulant actions of the oral direct activated factor Xa inhibitors, rivaroxaban and apixaban, have not previously been directly compared. Objectives To compare directly the steady-state pharmacokinetics and anticoagulant effects of rivaroxaban and apixaban at doses approved for stroke prevention in patients with non-valvular atrial fibrillation. Methods Twenty-four healthy Caucasian male volunteers were included in this open-label, two-period crossover, phase 1 study (EudraCT number: 2015-002612-32). Volunteers were randomized to receive rivaroxaban 20 mg once daily or apixaban 5 mg twice daily for 7 days, followed by a washout period of at least 7 days before they received the other treatment. Plasma concentrations and anticoagulant effects were measured at steady state and after drug discontinuation. Results Overall exposure was similar for both drugs: the geometric mean area under the plasma concentration-time curve for the 0-24-h interval was 1830 µg h L-1 for rivaroxaban and 1860 µg h L-1 for apixaban. Rivaroxaban was associated with greater inhibition of endogenous thrombin potential (geometric mean area under the curve relative to baseline during the 0-24-h interval: 15.5 h versus 17.5 h) and a more pronounced maximal prolongation relative to baseline of prothrombin time (PT) (1.66-fold versus 1.14-fold) and activated partial thromboplastin time (APTT) (1.43-fold versus 1.16-fold) at steady state than apixaban. Conclusions Despite similar exposure to both drugs, rivaroxaban 20 mg once daily was associated with greater and more sustained inhibition of thrombin generation than apixaban 5 mg twice daily. Sensitive PT and APTT assays can be used to estimate the anticoagulant effects of rivaroxaban.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Inibidores do Fator Xa/administração & dosagem , Inibidores do Fator Xa/farmacocinética , Pirazóis/administração & dosagem , Pirazóis/farmacocinética , Piridonas/administração & dosagem , Piridonas/farmacocinética , Rivaroxabana/administração & dosagem , Rivaroxabana/farmacocinética , Adulto , Estudos Cross-Over , Esquema de Medicação , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/sangue , Alemanha , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Tempo de Tromboplastina Parcial , Valor Preditivo dos Testes , Tempo de Protrombina , Pirazóis/efeitos adversos , Pirazóis/sangue , Piridonas/efeitos adversos , Piridonas/sangue , Reprodutibilidade dos Testes , Rivaroxabana/efeitos adversos , Rivaroxabana/sangue , Trombina/metabolismo , Adulto Jovem
10.
Arch Toxicol ; 91(4): 1663-1670, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27770144

RESUMO

A physiologically based human kinetic model (PBHKM) was used to predict the in vivo ibuprofen dose leading to the same concentration-time profile as measured in cultured human hepatic cells (Truisi et al. in Toxicol Lett 233(2):172-186, 2015). We parameterized the PBHKM with data from an in vivo study. Tissue partition coefficients were calculated by an algorithm and also derived from the experimental in vitro data for the liver. The predicted concentration-time profile in plasma was in excellent agreement with human experimental data when the liver partition coefficient was calculated by the algorithm (3.01) demonstrating values in line with findings obtained from human postmortem tissues. The results were less adequate when the liver partition coefficient was based on the experimental in vitro data (11.1). The in vivo doses necessary to reach the in vitro concentrations in the liver cells were 3610 mg using the best fitting model with a liver partition coefficient of 3.01 compared to 2840 mg with the in vitro liver partition coefficient of 11.1. We found that this difference is possibly attributable to the difference between protein binding in vivo (99.9 %) and in vitro (nearly zero) as the partition coefficient is highly dependent on protein binding. Hence, the fraction freely diffusible in the liver tissue is several times higher in vitro than in vivo. In consequence, when extrapolating from in vitro to in vivo liver toxicity, it is important to consider non-intended in vitro/in vivo differences in the tissue concentration which may occur due to a low protein content of the medium.


Assuntos
Anti-Inflamatórios não Esteroides/metabolismo , Ibuprofeno/metabolismo , Fígado/metabolismo , Modelos Biológicos , Adulto , Algoritmos , Anti-Inflamatórios não Esteroides/administração & dosagem , Relação Dose-Resposta a Droga , Humanos , Ibuprofeno/administração & dosagem , Fígado/citologia , Masculino , Ligação Proteica , Distribuição Tecidual
11.
J Clin Pharm Ther ; 41(6): 718-721, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27670839

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Tocilizumab (TCZ) is a humanized monoclonal antibody acting against the IL-6 receptor. It is a drug used in the treatment of rheumatoid arthritis and can be either given intravenously every 4 weeks or subcutaneously once a week. Known adverse events (AE) associated with TCZ include: infections of the upper respiratory tract, arterial hypertension, hypercholesterolaemia and hypertriglyceridaemia. Here, we present the first well-documented case of TCZ-induced acute pancreatitis (AP) and a systematic review of the literature including data from the Food and Drug Administration Adverse Event Reporting System (FAERS) database. METHODS: Patient data collection was performed within the Berlin Case-Control Surveillance Study. A literature search for TCZ-induced AP was conducted. Analysis of the FAERS database concerning TCZ-associated pancreatic AE from the period of 2009 until the first quarter of 2013 was conducted. RESULTS AND DISCUSSION: A 40-year-old man presented with a 2-day history of progressive upper abdominal pain with elevated serum lipase and triglyceride levels. Biliary pancreatitis was ruled out by abdominal sonography and CT scan. Cessation of intravenously administered TCZ resulted in improvement of the patient's condition and a decline in elevated laboratory values, suggesting a probable relationship between TCZ intake and AP. Analysis of the FAERS database retrieved 52 cases of TCZ-associated AP that accounted for 70% of all pancreatic AE in association with TCZ use. Further literature search detected three additional cases in which TCZ use was associated with AP. WHAT IS NEW AND CONCLUSION: Physicians should be aware of the probable association between TCZ use and AP. Targeted post-authorization studies are needed to confirm and quantify the risk of TCZ-induced AP.


Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Pancreatite/induzido quimicamente , Adulto , Sistemas de Notificação de Reações Adversas a Medicamentos , Humanos , Masculino , Estados Unidos , United States Food and Drug Administration
12.
Internist (Berl) ; 57(6): 616-23, 2016 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-27224991

RESUMO

BACKGROUND: Pharmacovigilance is defined as the activities relating to the detection, assessment, and prevention of adverse drug reactions (ADRs). Although its beginnings in Germany date back more than 50 years, a stagnation in this field has been observed lately. OBJECTIVES: Different tools of pharmacovigilance will be illustrated and the reasons for its stagnation in Germany will be elucidated. CURRENT DATA: Spontaneous reporting systems are an important tool in pharmacovigilance and are based on reports of ADRs from treating physicians, other healthcare professionals, or patients. Due to several weaknesses of spontaneous reporting systems such as underreporting, media bias, confounding by comorbidity or comedication, and due to the limited quality of the reports, the development of electronic healthcare databases was publicly funded in recent years so that they can be used for pharmacovigilance research. In the US different electronic healthcare databases were merged in a project sponsored by public means resulting in more than 193 million individuals. In Germany the establishment of large longitudinal databases was never conceived as a public duty and has not been implemented so far. Further attempts to use administrative healthcare data for pharmacovigilance purposes are severely restricted by the Code of Social Law (Section 75, Book 10). This situation has led to a stagnation in pharmacovigilance research in Germany. CONCLUSIONS: Without publicly funded large longitudinal healthcare databases and an amendment of Section 75, Book 10, of the Code of Social Law, the use of healthcare data in pharmacovigilance research in Germany will remain a rarity. This could have negative effects on the medical care of the general population.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos/economia , Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Registros Eletrônicos de Saúde/estatística & dados numéricos , Notificação de Abuso , Farmacovigilância , Sistemas de Notificação de Reações Adversas a Medicamentos/legislação & jurisprudência , Registros Eletrônicos de Saúde/economia , Registros Eletrônicos de Saúde/legislação & jurisprudência , Alemanha , Política de Saúde/economia , Política de Saúde/legislação & jurisprudência , Humanos
13.
Clin Pharmacol Ther ; 100(1): 63-6, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26850569

RESUMO

Hospital systems increasingly utilize pharmacogenomic testing to inform clinical prescribing. Successful implementation efforts have been modeled at many academic centers. In contrast, this report provides insights into the formation of a pharmacogenomics consultation service at a safety-net hospital, which predominantly serves low-income, uninsured, and vulnerable populations. The report describes the INdiana GENomics Implementation: an Opportunity for the UnderServed (INGENIOUS) trial and addresses concerns of adjudication, credentialing, and funding.


Assuntos
Farmacogenética/organização & administração , Provedores de Redes de Segurança/organização & administração , Populações Vulneráveis , Centros Médicos Acadêmicos/organização & administração , Humanos , Pessoas sem Cobertura de Seguro de Saúde , Pobreza
14.
Clin Res Cardiol ; 105(2): 117-26, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26195125

RESUMO

BACKGROUND: New oral anticoagulants are increasingly used in women of childbearing age, but apart from one case report there is no published experience with rivaroxaban exposure during pregnancy. METHODS: From October 2008 to December 2014, the German Embryotox Pharmacovigilance Centre identified 63 exposed pregnancies among 94 requests concerning rivaroxaban use during childbearing age. Follow-up included paediatric checks until 6 weeks after birth. RESULTS: All pregnancies with completed follow-up were exposed at least during the first trimester. Treatment indications included venous thromboembolism, knee surgery, and atrial fibrillation. 37 pregnancies were prospectively ascertained and resulted in six spontaneous abortions, eight elective terminations of pregnancy, and 23 live births. All women had discontinued rivaroxaban after recognition of pregnancy, mostly in the first trimester, but in one woman treatment continued until gestational week 26. There was one major malformation (conotruncal cardiac defect) among the 37 prospectively ascertained pregnancies in a woman with complex medication and a previous foetus with cardiac malformation without exposure to rivaroxaban. Only one case of bleeding concerning a retrospective report of surgery for missed abortion was observed in our case series. CONCLUSION: Our results might give reassurance to those women, who were inadvertently exposed to rivaroxaban in early pregnancy. However, our limited cohort size does not allow ruling out an increased malformation risk and does not support the use of rivaroxaban during pregnancy. In all cases of (inadvertent) rivaroxaban exposure during 1st trimester, anticoagulation regimen should be reconsidered and a detailed ultrasound assessment recommended to confirm normal foetal development.


Assuntos
Anticoagulantes/administração & dosagem , Resultado da Gravidez , Rivaroxabana/administração & dosagem , Tromboembolia/prevenção & controle , Adulto , Anticoagulantes/efeitos adversos , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Feminino , Seguimentos , Alemanha , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Humanos , Farmacovigilância , Gravidez , Complicações na Gravidez/tratamento farmacológico , Complicações na Gravidez/epidemiologia , Estudos Prospectivos , Estudos Retrospectivos , Risco , Rivaroxabana/efeitos adversos , Tromboembolia/etiologia
15.
Br J Pharmacol ; 172(17): 4406-18, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26075500

RESUMO

BACKGROUND AND PURPOSE: The Munich Wistar Frömter (MWF) rat strain represents an experimental model to study cardiovascular alterations under conditions of progressive albuminuria. The aim of this study was to evaluate the association between genetic predisposition to albuminuria and the development of arterial stiffness and/or vascular remodelling. EXPERIMENTAL APPROACH: Experiments were performed in mesenteric arteries from 12-week-old MWF, Wistar Kyoto (WKY) and consomic MWF-6(SHR) and MWF-8(SHR) rats in which chromosomes 6 or 8 associated with albuminuria from MWF were replaced by the respective chromosome from spontaneously hypertensive rats (SHR). KEY RESULTS: Incremental distensibility, wall stress and strain were reduced, and arterial stiffness was significantly increased in albuminuric MWF compared with WKY. Albuminuria suppression in both consomic strains was associated with lower ß-values in MWF-8(SHR) and MWF-6(SHR) compared with MWF. Moreover, elastin content was significantly lower in MWF external elastic lamina compared with WKY and both consomic strains. In addition, a reduction in arterial external and internal diameter and cross-sectional area was detected in MWF compared with WKY, thus exhibiting an inward hypotrophic remodelling. However, these alterations remained unchanged in both consomic strains. CONCLUSION AND IMPLICATIONS: These data demonstrate that albuminuria in MWF is associated with increased arterial stiffness due to a reduction of elastin content in the external elastic lamina. Moreover, inward hypotrophic remodelling in MWF is not directly associated with albuminuria. In contrast, we demonstrated that two major genetic loci affect both the development of albuminuria and arterial stiffness, thus linking albuminuria and impairment of mechanical properties of resistance arteries.


Assuntos
Albuminúria/genética , Elastina/fisiologia , Predisposição Genética para Doença/genética , Rigidez Vascular/fisiologia , Albuminúria/fisiopatologia , Animais , Masculino , Artérias Mesentéricas/fisiopatologia , Técnicas de Cultura de Órgãos , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Vasoconstrição/fisiologia
16.
Eur J Pain ; 19(9): 1331-41, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25690438

RESUMO

BACKGROUND: To evaluate the effect of interventions for general practitioners and nursing home staff to improve pain severity and appropriateness of pain medication in nursing home residents (NHR). METHODS: This cluster-randomized controlled trial was conducted in six nursing homes in the intervention and control group, respectively. Pain management was analysed before (T0) and after (T1, T2) an educational intervention in 239 NHR, aged ≥65 years, without moderate or severe cognitive impairment. Primary and secondary outcomes were average pain severity and appropriateness of pain medication as determined with the Numeric Rating Scale and Pain Medication Appropriateness Scale (PMASD ), respectively. RESULTS: At T0, 72.2% and 73.7% of NHR (mean age 83 years) reported pain (average pain severity 2.4) in the intervention and control group, respectively. The PMASD at T0 was 53.9 in the intervention group and 60.8 in the control group (p = 0.12), while 20.6% compared to 6.9% (p = 0.009) received no pain medication in the two groups. At T2, non-significant improvements in the average pain severity (1.59) and PMASD (61.07) were observed in the intervention group. Moreover, the mean individual PMASD increased by 8.09 (p = 0.03) and the proportion of NHR without pain medication decreased by 50% (p = 0.03) in the intervention group. No appreciable changes were found in the control group at T2. CONCLUSIONS: NHR exhibited a high prevalence of pain with overall low severity, while a high proportion of individuals received inappropriate pain medications. Both findings were not significantly improved by the intervention, although some aspects of drug treatment were meaningful improved.


Assuntos
Analgésicos/uso terapêutico , Instituição de Longa Permanência para Idosos , Casas de Saúde , Manejo da Dor/métodos , Dor/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Feminino , Alemanha/epidemiologia , Instituição de Longa Permanência para Idosos/estatística & dados numéricos , Humanos , Masculino , Casas de Saúde/estatística & dados numéricos , Dor/epidemiologia , Manejo da Dor/estatística & dados numéricos , Índice de Gravidade de Doença
17.
Herz ; 40 Suppl 2: 209-16, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25630386

RESUMO

AIMS: This study investigated the incidence of hypertensive target organ damage (TOD), control of cardiovascular risk factors, and the short-term prognosis in hypertensive patients under contemporary guideline-oriented therapy. PATIENTS AND METHODS: A total of 1,377 consecutive patients (mean age 58.2 ± 9.9 years, 82.2 % male) with arterial hypertension were included in the ESTher (Endorganschäden, Therapie und Verlauf - target organ damage, therapy, and course) registry at 15 rehabilitation clinics within the framework of the National Genome Research Network. Cardiovascular risk factors, medication, comorbidities, and glomerular filtration rate (GFR) were assessed. Left ventricular hypertrophy (LVH), left ventricular mass (LVM), left ventricular mass index (LVMI), and left ventricular ejection fraction (LVEF) were determined by two-dimensional echocardiography. The mean follow-up was 513 ± 159 days. Changes in continuous parameters were tested by the t test, changes in discrete characteristics are presented by means of transition tables and tested with the McNemar test. RESULTS: The mean LVEF was 59.3 ± 9.9 %, both mean LVM (238.6 ± 101.5 g) and LVMI (54.0 ± 23.6 g/m(2.7)) were increased while relative wall thickness (RWT, 0.46 ± 0.18) indicated the presence of concentric LVH. Of the patients, 10.2 % displayed renal dysfunction (estimated GFR < 60 ml/min/1.73 m(2)). The 1.5-year overall mortality was 1.2 %. Compared with discharge, at follow-up the proportion of patients with blood pressure (BP) values < 140/90 mmHg decreased from 68.7 % to 55.0 % (p < 0.001) and with low-density lipoprotein (LDL) values < 100 mg/dl from 62.6 % to 38.1 % (p < 0.001). At follow-up significantly more patients displayed a GFR value of < 60 ml/min/1.73 m(2) (10.2 % vs. 16.0 %, p < 0.001). CONCLUSION: A significant proportion of hypertensive rehabilitation participants displayed TOD including LVH and renal dysfunction. Even after stringent BP reduction, a considerable increase in nephropathy could be found after 18 months.


Assuntos
Hipertensão/mortalidade , Hipertrofia Ventricular Esquerda/mortalidade , Sistema de Registros , Insuficiência Renal/mortalidade , Disfunção Ventricular Esquerda/mortalidade , Comorbidade , Medicina Baseada em Evidências , Feminino , Alemanha/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Órgãos em Risco , Fatores de Risco , Taxa de Sobrevida
18.
Dtsch Med Wochenschr ; 139(48): 2441-7, 2014 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-25409401

RESUMO

BACKGROUND AND AIM: Arterial hypertension is a common health problem in older nursing home residents (NHR). The aim of this study was to prospectively analyze blood pressure (BP) patterns, antihypertensive therapy, and visit-to-visit BP variability in NHR. METHODS: BP, visit-to-visit variability (estimated by standard deviation of means) of systolic BP (SBP) were analyzed in 12 nursing homes in Germany. NHR who were at least 65 years old and had no moderate or severe dementia were studied at baseline (T0), after 3 and 6 months, respectively. RESULTS: BP data were available for 177 NHR (mean age 83.8, 69.5% female) at T0.  A total of 90.4% NHR was affected by hypertension. Mean systolic/diastolic blood pressure was 130,1/75,5 mmHg. BP values of ≥ 140/90 mmHg were found in 29.9%, while 33.9% of NHR exhibited SBP values < 120 mmHg. At least one antihypertensive drug was used in 84.2%, and 40.7% of NHR were treated with at least three different drugs. The median of the visit-to-visit SBP variability was 9.05 (Min. 0, Max. 35.78); an influence of age, sex, and type of antihypertensive medication was not found. CONCLUSION: Elderly German NHR showed a high prevalence of hypertension and BP was controlled in 80%. However, a large proportion received intensive BP lowering pharmacotherapy and exhibited SBP values clearly lower than recommend target values between 140 and 150 mmHg particularly for elderly patients over 80 years. Thus, to avoid overtreatment BP should be monitored closely to adapt antihypertensive therapy in this population.


Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Instituição de Longa Permanência para Idosos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Casas de Saúde , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Quimioterapia Combinada , Feminino , Seguimentos , Alemanha , Inquéritos Epidemiológicos , Humanos , Hipertensão/epidemiologia , Masculino , Resultado do Tratamento
19.
Dtsch Med Wochenschr ; 139(48): 2457-62, 2014 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-25409405

RESUMO

Hypertension and alcohol use are both part of the five most important risk factors for burden of disease in Western Europe, mainly because of their impact on non-communicable diseases (NCD). Both risk factors are prevalent with high overlap among patients in primary care. Implementation of a screening for alcohol among patients of hypertension in primary care followed by brief intervention for problem alcohol use or formal treatment for people with alcohol dependence could constitute an important step to reach the goals of the Global WHO Action Plan for Prevention and Control of NCD. In addition, such an intervention could improve the management of hypertension. In a working group of experts from clinical practice and research the rationale and potential barriers for this intervention were discussed and steps for implementation in primary care were developed.


Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Alcoolismo/diagnóstico , Alcoolismo/reabilitação , Hipertensão/etiologia , Hipertensão/reabilitação , Programas de Rastreamento , Seguimentos , Humanos , Hipertensão/prevenção & controle , Atenção Primária à Saúde , Fatores de Risco
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