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BACKGROUND: The progress of electronic health technologies and biobanks holds enormous promise for efficient research. Evidence shows that studies based on sharing and secondary use of data/samples have the potential to significantly advance medical knowledge. However, sharing of such resources for international collaboration is hampered by the lack of clarity about ethical and legal requirements for transfer of data and samples across international borders. MAIN TEXT: Here, the International Clinical Trial Center Network (ICN) reports the legal and ethical requirements governing data and sample exchange (DSE) across four continents. The most recurring requirement is ethical approval, whereas only in specific conditions approval of national health authorities is required. Informed consent is not required in all sharing situations. However, waiver of informed consent is only allowed in certain countries/regions and under certain circumstances. The current legal and ethical landscape appears to be very complex and under constant evolution. Regulations differ between countries/regions and are often incomplete, leading to uncertainty. CONCLUSION: With this work, ICN illuminates the unmet need for a single international collaborative framework to facilitate DSE. Harmonising requirements for global DSE will reduce inefficiency and waste in research. There are many challenges to realising this ambitious vision, including inconsistent terminology and definitions, and heterogeneous and dynamic legal constraints. Here, we identify areas of agreement and significant difference as a necessary first step towards facilitating international collaboration. We propose the establishment of a working group to continue the comparison across jurisdictions, create a standardised glossary and define a set of basic principles and fundamental requirements for DSE.
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Registros Eletrônicos de Saúde/ética , Registros Eletrônicos de Saúde/legislação & jurisprudência , Disseminação de Informação/ética , Disseminação de Informação/legislação & jurisprudência , Cooperação Internacional/legislação & jurisprudência , Bancos de Tecidos/ética , Bancos de Tecidos/legislação & jurisprudência , Saúde Global , Humanos , Internacionalidade , Propriedade/ética , Propriedade/legislação & jurisprudênciaRESUMO
Introduction This study aimed to evaluate drug-drug interactions (DDIs) and their association with the quality of life in patients with hypertension. Materials and methods This cross-sectional study included 123 patients with hypertension. DDIs were evaluated using the Medscape Drug Interaction Checker Database (Medscape, New York, NY). The EuroQol-5D (EQ-5D) Quality of Life Scale was used for each patient. Results The overall blood pressure control rate (systolic/diastolic blood pressure levels, <140/90 mmHg) was 43% (53/123). The age of the patients with uncontrolled hypertension was higher than the patients with controlled hypertension (63.67 ± 11.00 vs. 58.42 ± 10.07 years; p = 0.007). The number of DDIs showed significant correlations, positively with age (r = 0.303, p = 0.001), total number of drugs (r = 0.784, p < 0.001), number of antihypertensive drugs (r = 0.640, p < 0.001), and body mass index (BMI) (r = 0.321, p < 0.001) and inversely with EQ-5D index score (r = -0.247, p = 0.006). The EQ-5D index and visual analog score were inversely correlated with age and BMI. Additional significant linear correlations between age and the total number of drugs, age and number of the antihypertensive drugs, the number of antihypertensive drugs and BMI, and the number of total drugs and BMI were detected. Of a total of 511 identified DDIs, 14 interactions in 12 patients were considered serious, 402 interactions in 82 patients were considered significant, and 95 interactions in 39 patients were considered minor. Conclusions This study supports that DDIs have important associations with antihypertensive treatment and the quality of life of patients. Higher age and BMI values were associated with a higher risk of DDIs and lower quality of life in patients with hypertension.
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Background Diabetes mellitus is an important risk factor for dementia, Alzheimer's disease, and other neurodegenerative diseases. Recent findings have made the relationship between the inhibition of the dipeptidyl peptidase-4 (DPP-4) enzyme and cognitive functions an important research topic. Objective This study aimed to evaluate the association between DPP-4 inhibitor use and cognitive functions, serum brain-derived neurotrophic factor (BDNF), and pentraxin-3 (PTX-3) levels in patients with type 2 diabetes, compared with the patients who only use metformin treatment. Design, patients, and methods A total of 50 patients with type 2 diabetes (hemoglobin A1c levels at ≤%7.5) who were under treatment with metformin±DPP-4 inhibitor (n=25) or only metformin (n=25) were included in this cross-sectional study. Serum BDNF and PTX-3 levels were assessed using an enzyme-linked immunosorbent assay. A standardized mini-mental test (sMMSE) was used to evaluate cognitive functions. Results There were no significant differences in the characteristics of the study groups. The mean sMMSE score of the patients receiving DPP-4±metformin treatment was statistically higher when compared with patients receiving only metformin treatment (27.16±1.95 vs. 25.40±3.07; p=0.041). The BDNF levels of the patients receiving DPP-4±metformin treatment were considerably higher than the patients receiving only metformin treatment (394.51±205.66 ng/ml vs. 180.63±297.94 ng/ml; p=0.001). The difference in PTX-3 levels between study groups was not statistically significant (5.47±3.44 vs. 3.79±2.53; p=0.055). Conclusion When compared to metformin alone, the use of DPP-4 inhibitors in the treatment of patients with type 2 diabetes was associated with increased serum BDNF levels and improved cognitive functions.
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CONTEXT: Stress triggers a cascade of reactions that alter the organism's dynamic steady state. There is a scarcity of interventional studies that show cortisol variability upon stress over time in groups of patients with chronic noncommunicable diseases and comorbidities. OBJECTIVE: We aimed to examine salivary cortisol changes in the cognitive stress response of patients with hypertension and diabetes mellitus (HT&DM) and patients with hypertension (HT) and to determine differences between them. METHODS: The study was conducted using a stress test of solving an arithmetic task in 62 patients with HT&DM and HT who were being treated in the outpatient clinic of the Medical Pharmacology and Clinical Pharmacology Department in Istanbul University, Istanbul Medical Faculty Hospital. RESULTS: There was no statistically significant difference between the HT&DM and HT groups for systolic blood pressure (SBP) and diastolic blood pressure (DBP) values (P = .331 and P = .058). When measured by repeated ANOVA, salivary cortisol level [F (1.842, 60) = 8.771, P < .0001], SBP [F (2.185, 60) = 12.080, P < .0001], DBP [F (2.793, 60) = 6.043, P = .001], and heart rate [F (2.073, 60) = 13.259, P < .0001] were statistically significant for the main effect (time), while the effect of the group × time interaction factor was statistically not significant (P = .773; P = .751; P = .713 and P = .506, respectively). CONCLUSION: The arithmetic problem-solving task used with the HT&DM and HT patients was useful as an acute stress test in the laboratory environment. There was no statistically significant difference for group × time interaction factor between the HT&DM and HT groups; however, the salivary cortisol and BP values increased significantly after acute stress within each group.
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Diabetes Mellitus , Hipertensão , Pessoa de Meia-Idade , Humanos , Masculino , Hidrocortisona/uso terapêutico , Hipertensão/tratamento farmacológico , Pressão Sanguínea , ComorbidadeRESUMO
Background: Adverse events of special interest (AESIs) were pre-specified to be monitored for the COVID-19 vaccines. Some AESIs are not only associated with the vaccines, but with COVID-19. Our aim was to characterise the incidence rates of AESIs following SARS-CoV-2 infection in patients and compare these to historical rates in the general population. Methods: A multi-national cohort study with data from primary care, electronic health records, and insurance claims mapped to a common data model. This study's evidence was collected between Jan 1, 2017 and the conclusion of each database (which ranged from Jul 2020 to May 2022). The 16 pre-specified prevalent AESIs were: acute myocardial infarction, anaphylaxis, appendicitis, Bell's palsy, deep vein thrombosis, disseminated intravascular coagulation, encephalomyelitis, Guillain- Barré syndrome, haemorrhagic stroke, non-haemorrhagic stroke, immune thrombocytopenia, myocarditis/pericarditis, narcolepsy, pulmonary embolism, transverse myelitis, and thrombosis with thrombocytopenia. Age-sex standardised incidence rate ratios (SIR) were estimated to compare post-COVID-19 to pre-pandemic rates in each of the databases. Findings: Substantial heterogeneity by age was seen for AESI rates, with some clearly increasing with age but others following the opposite trend. Similarly, differences were also observed across databases for same health outcome and age-sex strata. All studied AESIs appeared consistently more common in the post-COVID-19 compared to the historical cohorts, with related meta-analytic SIRs ranging from 1.32 (1.05 to 1.66) for narcolepsy to 11.70 (10.10 to 13.70) for pulmonary embolism. Interpretation: Our findings suggest all AESIs are more common after COVID-19 than in the general population. Thromboembolic events were particularly common, and over 10-fold more so. More research is needed to contextualise post-COVID-19 complications in the longer term. Funding: None.
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The effect of antihypertensive drugs, especially drugs modulating the renin-angiotensin-aldosterone-system (RAAS), on neurodegenerative diseases still needs to be investigated. This study aimed to compare the effects of three different antihypertensive drugs (telmisartan, perindopril, and nebivolol) on neuroprotection and acetylcholine (ACh) levels against lipopolysaccharide (LPS)-induced injury in a differentiated SH-SY5Y cell line. Cells were treated with retinoic acid for differentiation to a neuronal phenotype. LPS 20 (µg/mL) was applied to the cells for one hour. Then, the cells were treated with 1, 5, and 10 µg/mL concentrations of telmisartan, perindopril, and nebivolol separately for 24 hours, except for the control and LPS alone groups. Cell viability was evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. ACh levels were analyzed using an enzyme immunosorbent assay in the culture medium. Tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1ß), and nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) expressions were evaluated using western blot analysis. Telmisartan demonstrated the highest cell viability against LPS-induced injury, whereas the protective effect of perindopril was moderate. Nebivolol showed no neuroprotective effect. The protective effect of 10-µg/mL telmisartan was superior to 10 µg/mL perindopril (p=0.006), 5 µg/mL perindopril (p=0.001), 1 µg/mL perindopril (p=0.001), and 1, 5, and 10 µg/mL nebivolol (p<0.001). Among all the study drugs, only telmisartan provided a statistically significant increase in ACh levels after LPS-induced injury. Additionally, the administration of telmisartan provided a concentration-dependent reduction in TNF-α, IL-1ß, and NFκB expression against LPS-induced neuroinflammation. These findings suggest that telmisartan has a superior neuroprotective effect against LPS-induced injury in neuron-like cells compared with both perindopril and nebivolol.
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BACKGROUND: Tricuspid regurgitation is a condition that affects 1.6 million patients in the United States and is independently associated with morbidity and mortality. The TriClip™ procedure repairs the tricuspid valve without the need for open-heart surgery. The aim of this study is to evaluate the cost-effectiveness of TriClip™ treatment in patients with advanced tricuspid regurgitation from the Turkish reimbursement agency perspective. METHODS: Within the scope of this study, the general literature was searched in order to reach data on tricuspid regurgitation. The utilization of health care services used in the expert panel was re-calculated with the current reimbursement costs to determine the cost of heart failure in Turkey. In this study, Markov analysis, Tornado analysis, cost-effectiveness analysis, and partitioned survival analysis have been performed to determine whether TriClip™ is an effective treatment method compared to medication treatment. RESULTS: In according to calculations, 5-year survival rate was found as 49.91% for medication treatment and 57.64% for TriClip™ treatment. According to the analysis performed, the cost of medication treatment was calculated as 3879.72 and TriClip™ Transcatheter Tricuspid Valve Repair System treatment as 25 661.15 for a 60-month period in patients with tricuspid regurgitation and New York Heart Association III-IV. In the calculation, it was found that TriClip™ treatment gave patients an average of 1.64 life years and it was found to be cost-effective compared to medication treatment. CONCLUSIONS: Considering the positive effect of TriClip™ treatment on patients with tricuspid regurgitation in terms of mortality and regression of the heart failure stage, as recommended in the guidelines, widespread of its use has great importance.
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Procedimentos Cirúrgicos Cardíacos , Insuficiência Cardíaca , Insuficiência da Valva Tricúspide , Procedimentos Cirúrgicos Cardíacos/métodos , Análise Custo-Benefício , Humanos , Valva Tricúspide/cirurgia , Insuficiência da Valva Tricúspide/cirurgiaRESUMO
OBJECTIVE: This study aimed to evaluate the effects of potential risk factors on antihypertensive treatment success. METHODS: Patients with hypertension who were treated with antihypertensive medications were included in this study. Data from the last visit were analyzed retrospectively for each patient. To evaluate the predictive models for antihypertensive treatment success, data mining algorithms (logistic regression, decision tree, random forest, and artificial neural network) using 5-fold cross-validation were applied. Additionally, study parameters between patients with controlled and uncontrolled hypertension were statistically compared and multiple regression analyses were conducted for secondary endpoints. RESULTS: The data of 592 patients were included in the analysis. The overall blood pressure control rate was 44%. The performance of random forest algorithm (accuracy = 97.46%, precision = 97.08%, F1 score = 97.04%) was slightly higher than other data mining algorithms including logistic regression (accuracy = 87.31%, precision = 86.21%, F1 score = 85.74%), decision tree (accuracy = 76.94%, precision = 70.64%, F1 score = 76.54%), and artificial neural network (accuracy = 86.47%, precision = 83.85%, F1 score = 84.86%). The top 5 important categorical variables (predictive correlation value) contributed the most to the prediction of antihypertensive treatment success were use of calcium channel blocker (-0.18), number of antihypertensive medications (0.18), female gender (0.10), alcohol use (-0.09) and attendance at regular follow up visits (0.09), respectively. The top 5 numerical variables contributed the most to the prediction of antihypertensive treatment success were blood urea nitrogen (-0.12), glucose (-0.12), hemoglobin A1c (-0.12), uric acid (-0.09) and creatinine (-0.07), respectively. According to the decision tree model; age, gender, regular attendance at follow-up visits, and diabetes status were identified as the most critical patterns for stratifying the patients. CONCLUSION: Data mining algorithms have the potential to produce predictive models for screening the antihypertensive treatment success. Further research on larger populations and longitudinal datasets are required to improve the models.
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Anti-Hipertensivos , Hipertensão , Humanos , Anti-Hipertensivos/efeitos adversos , Estudos Retrospectivos , Mineração de Dados , Fatores de Risco , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologiaRESUMO
OBJECTIVE: Clinical research has faced new challenges during the COVID-19 pandemic, leading to excessive operational demands affecting all stakeholders. We evaluated the impact of COVID-19 on clinical research strategies and compared different adaptations by regulatory bodies and academic research institutions in a global context, exploring what can be learned for possible future pandemics. METHODS: We conducted a cross-sectional online survey and identified and assessed different COVID-19-specific adaptation strategies used by academic research institutions and regulatory bodies. RESULTS: All 19 participating academic research institutions developed and followed similar strategies, including preventive measures, manpower recruitment, and prioritisation of COVID-19 projects. In contrast, measures for centralised management or coordination of COVID-19 projects, project preselection, and funding were handled differently amongst institutions. Regulatory bodies responded similarly to the pandemic by implementing fast-track authorisation procedures for COVID-19 projects and developing guidance documents. Quality and consistency of the information and advice provided was rated differently amongst institutions. CONCLUSION: Both academic research institutions and regulatory bodies worldwide were able to cope with challenges during the COVID-19 pandemic by developing similar strategies. We identified some unique approaches to ensure fast and efficient responses to a pandemic. Ethical concerns should be addressed in any new decision-making process.
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COVID-19 , Adaptação Psicológica , COVID-19/epidemiologia , Estudos Transversais , Humanos , Pandemias/prevenção & controle , Inquéritos e QuestionáriosRESUMO
The aim of the present study was to evaluate the efficacy and safety of S-amlodipine 2.5 and 5 mg/d in patients with hypertension who were treatment-naive or previously received antihypertensive monotherapy. During the 8-week treatment period, all patients received S-amlodipine 2.5 mg/d for the first 4 weeks, followed by S-amlodipine 5 mg/d for the second 4 weeks. For efficacy assessments, ambulatory and office blood pressure (BP) measurements were performed during the baseline, fourth-week, and eighth-week visits. For safety assessments, all adverse events and abnormal laboratory findings were recorded. This study is registered with ClinicalTrials.gov (NCT03038451). Of 43 patients evaluated at the screening visit, 33 were enrolled. In the treatment-naive arm, significant reductions in both office and ambulatory systolic BP (SBP) and diastolic BP (DBP) were observed with S-amlodipine 2.5 mg/d and additional significant reductions were achieved with dose titration (S-amlodipine 5 mg/d). At the end of the study, the rate of the treatment-naive patients with BP under control (SBP/DBP <140/90 mm Hg) was 53% with S-amlodipine 2.5 mg and increased to 78% with S-amlodipine 5 mg. For the noninferiority evaluation, S-amlodipine 2.5 and 5 mg/d treatments were generally noninferior to both office and ambulatory BP levels achieved with the medications that the patients received before participating in the study. Five nonserious adverse events likely to be associated with the study drug were observed. No serious adverse event was encountered. Consequently, S-amlodipine can be suggested as an effective and safe treatment option for patients with hypertension.
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Anlodipino/administração & dosagem , Anti-Hipertensivos/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/administração & dosagem , Hipertensão/tratamento farmacológico , Adulto , Anlodipino/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Bloqueadores dos Canais de Cálcio/efeitos adversos , Substituição de Medicamentos , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , TurquiaRESUMO
Renin Angiotensin Aldosterone System (RAAS) plays an important role in the development of hypertension. On the other hand, hypertension is a well-known and independent risk factor for cognitive impairment. The aim of the present study was to evaluate the relationship of blood pressure control, plasma angiotensin peptides and aldosterone with cognitive functions. Forty-one patients who were under treatment with the same antihypertensive medications for at least three months were included in the study. Plasma angiotensin II, angiotensin 1-7, angiotensin IV, and aldosterone concentrations were analyzed using an enzyme-linked immunosorbent assay (ELISA). Standardized Mini Mental State Examination (SMMSE) was used to evaluate cognitive functions. When the participants were grouped according to their SMMSE scores (cut-off value: 26 points), we determined significant differences between systolic blood pressure (SBP) levels, diastolic blood pressure levels, plasma angiotensin II and angiotensin 1-7 concentrations of the groups. When the participants were stratified according to their SBP levels (cut-off value: 140 mm Hg), we found significant differences in SMMSE scores and plasma angiotensin IV concentrations of the groups. A negative correlation between SBP and SMMSE scores and strong linear correlations among angiotensin peptides levels were determined. The relationship found between SBP and SMMSE in the present study was compatible with the literature. Our 33 patients were using at least one angiotensin II receptor blocker (ARB). Regarding AT1 receptor blockage, the significant association between higher SMMSE scores and increased angiotensin peptides may support a finding that ARBs prevent dementia and improve cognitive function. Further larger studies are needed to confirm and prove the relation of RAAS biochemical parameters with cognitive function.
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BACKGROUND: Gynecomastia is defined as benign proliferation of male breast glandular tissue. To date, the pathophysiology of adolescent gynecomastia (AG) remains unclear. Kisspeptin is a polypeptide that plays an important role in the regulation of the hypothalamic-pituitary-gonadal hormonal axis. In this study, we investigated whether there is a relationship between kisspeptin and AG. MATERIALS AND METHODS: This study included 40 males between 9 and 18 years of age diagnosed with gynecomastia. The control group consisted of 30 young healthy males in the same age range. The participants were evaluated with respect to anthropometric measurements (age, height, body weight, body mass index, breast and pubic stages and testicular volume). The levels of kisspeptin, follicle-stimulating hormone, luteinizing hormone, estradiol (E2), testosterone (T), and ratio of E2 to T were measured in both groups. RESULTS: The mean age was 13.8 years. There were no differences between the groups in terms of anthropometric parameters, plasma gonadotropin levels, estrogen levels, and E2/T (P > 0.05). Plasma kisspeptin (0.77 and 0.54 ng/mL, P < 0.05) and T (253.9 ng/dL and 117.9 ng/dL) levels were significantly higher in the AG group than in the control group (P < 0.001). CONCLUSION: Kisspeptin levels are an important factor in AG.
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Ginecomastia/sangue , Kisspeptinas/sangue , Adolescente , Estudos de Casos e Controles , Criança , Ginecomastia/etiologia , Humanos , Masculino , Fatores de RiscoAssuntos
Amidas , Anti-Hipertensivos , Infecções por Coronavirus/tratamento farmacológico , Fumaratos , Pneumonia Viral/tratamento farmacológico , Enzima de Conversão de Angiotensina 2 , Betacoronavirus , COVID-19 , Humanos , Pandemias , Peptidil Dipeptidase A , Sistema Renina-Angiotensina/efeitos dos fármacos , Sistema Renina-Angiotensina/fisiologia , SARS-CoV-2RESUMO
The coexistence of hypertension and diabetes increases the incidence of cardiovascular events and long-term morbidity and mortality. Blood pressure should be controlled with the most appropriate drugs as well as tight blood glucose control in patients with diabetes and hypertension. RAAS (Renin Angiotensin Aldosterone System) blockers have an important role in the treatment of these patients, in this sense, ACEi and ARB remained the major treatment option in hypertension guidelines. The most recent RAAS blocker to be approved by the FDA was aliskiren in 2007, a renin inhibitor. Studies showed that aliskiren is as effective as other antihypertensive drugs and has a safety profile similar to placebo. The potent renin inhibitor aliskiren directly inhibits the RAAS system at its rate limiting step and differently from other RAAS blockers; it decreases plasma renin activity (PRA). Although the relationship of increased PRA levels and cardiovascular risk has been shown, it is unclear if the PRA decrease provided by aliskiren has an impact on clinical outcomes and cardiovascular endpoints. On the other hand, large trials like ASPIRE, AVANT-GARDE, ALTITUDE, ASTRONAUT, which investigated the combination of aliskiren with other RAAS blockers, failed to show the expected outcomes or resulted with an increased incidence of adverse effects, which raised more questions. As a result of the ALTITUDE trial, combination of aliskiren with an ACEi or ARB is not recommended in patients with hypertension and diabetes, or at least moderate renal dysfunction. Trials designed to prove aliskiren's efficacy in new indications like diabetes, may face similar problems related to dual RAAS blockade because in the majority of cases, the optimal treatment is achieved with an ACEi or ARB. In this conjuncture, the increase in adverse events seen with aliskiren might be related to dual RAAS blockade rather than aliskiren directly. For instance, it is unclear whether the adverse event incidence would be the same, less, or higher if ALTITUDE was designed to investigate ACEi and ARB combination without aliskiren. In fact, every new molecular entity and mechanism of action faces the same barriers. For the time being, differentiating points like PRA lowering effects as an add-on therapy to calcium channel blockers or hydrochlorothiazide, and the populations that might have additional benefit, should be carefully investigated.
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Aliskiren is the newest antihypertensive drug and the first orally active direct renin inhibitor to become available for clinical use. Clinical data have substantiated that the antihypertensive effectiveness of aliskiren is similar to that of the other major antihypertensive agents. Furthermore, aliskiren has a similar safety profile to placebo. Combination treatment with aliskiren showed significant blood pressure and proteinuria reductions compared with monotherapy. Aliskiren decreases plasma renin activity in contrast to other renin-angiotensin-aldosterone related drugs. The efficacy of aliskiren in treating major cardiovascular events and the prevention of end-organ damage are being investigated in the ASPIRE HIGHER program. Although the first studies of the ASPIRE HIGHER program such as ALOFT, AVOID, AGELESS showed favorable findings, ASPIRE and AVANT-GARDE studies provided contradictory results. Subsequently, the ALTITUDE study was terminated early because of safety issues and lack of beneficial effects. Most recently, the ASTRONAUT trial showed no reduction in cardiovascular death or heart failure rehospitalization with the addition of aliskiren to standard therapy in patients who were hospitalized for heart failure and with reduced left-ventricular ejection fraction. The results of ongoing studies in other patient groups such as the ATMOSPHERE trial are awaited.
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Zinc is an essential micronutrient for human health. It is very important for body functions, and they have an interaction potential in several systems, including nervous system. Although there is no global regulation about the daily amounts, it is shown to reduce the incidence of diarrhea and pneumonia. Zinc deficiency is a global problem, especially in developing countries. Zinc has been shown to be effective in treatment of zinc deficiency, Acrodermatitis Enteropathica, protein energy malnutrition (PEM), Wilson disease, pica, diarrhea, unrecovering ulcers etc. Although under 50 mg daily is enough for diarrhea, anemia, infections, immundeficieny etc., higher dosages may be required in Wilson`s disease, pica and acrodermatitis enteropathica up to 220 mg daily. Also it was reported that high dosage of zinc treatment can lead neurotoxity, Alzheimer`s disease or impaired lipid metabolism. So caution should be exercised when prescribing the zinc to the patients who have risk for neurotoxity, Alzheimer`s disease or impaired lipid metabolism.