Efficacy of Aliskiren/Hydrochlorothiazide Combination for the Treatment of Hypertension: A Meta-Analytical Approach

Background: Single-pill combinations of aliskiren/hydrochlorothiazide have recently been approved by the European Medicines Agency for the treatment of hypertension. Objective: This study aimed to assess the antihypertensive efficacy of aliskiren/hydrochlorothiazide combination in reducing systolic and diastolic blood pressure in hypertensive patients. Methods: A search in International Pharmaceutical Abstracts, MEDLINE, The Cochrane Library and ISI Web of Knowledge was performed from 2000 to November 2009, to identify randomized, double-blind, clinical trials using aliskiren/hydrochlorothiazide for the treatment of hypertension. Studies were included if they evaluated the antihypertensive efficacy of aliskiren/hydrochlorothiazide in patients with mild or moderate essential hypertension and age 18 years. The meta-analytical approach calculated the weighted average reductions of systolic and diastolic blood pressure for each daily dosage combination. Results: We included 5 clinical trials testing several combinations of aliskiren/hydrochlorothiazide and containing data on 5448 patients. In all studies blood pressure was assessed at inclusion (baseline) and after 8 weeks of therapy. Blood pressure reductions and control rates were significantly (p < 0.05) higher with the aliskiren/hydrochlorothiazide combinations than with placebo and the same doses of aliskiren or hydrochlorothiazide alone. The weighted mean reductions (mm Hg) from baseline of systolic and diastolic blood pressure for each aliskiren/hydrochlorothiazide combination were: -15.8/- 10.3 (150/25 mg); -15.9/-11.8 (300/12.5 mg); -16.9/-11.6 (300/25 mg). Blood pressure control rates (%) for the above combinations were, at least, respectively: 43.8, 50.1 and 51.9. Conclusions: Aliskiren/hydrochlorothiazide provided clinically significant additional blood pressure reductions and improved blood pressure control rates over aliskiren or hydrochlorothiazide monotherapy.We thank the Fundação para a Ciência e a Tecnologia (FCT) for supporting the fellowship grant SFRH/BD/36756/ 2007 to Manuel Morgado

Towards a catalog of aspect-oriented refactorings

Comunicação aprovada à International Conference on Aspect-Oriented Software Development (AOSD), 4, Chicago, 2005.In this paper, we present a collection of aspect-oriented refactorings covering both the extraction of aspects from object-oriented legacy code and the subsequent tidying up of the resulting aspects. In some cases, this tidying up entails the replacement of the original implementation with a different, centralized design, made possible by modularization. The collection of refactorings includes the extraction of common code in various aspects into abstract superaspects. We review the traditional object-oriented code smells in the light of aspect-orientation and propose some new smells for the detection of crosscutting concerns. In addition, we propose a new code smell that is specific to aspects.(undefined

Blood pressure control and antihypertensive pharmacotherapy patterns in a hypertensive population of Eastern Central Region of Portugal

<p>Abstract</p> <p>Background</p> <p>Interventions to improve blood pressure control in hypertension have had limited success in clinical practice despite evidence of cardiovascular disease prevention in randomised controlled trials.</p> <p>The objectives of this study were to evaluate blood pressure control and antihypertensive pharmacotherapy patterns in a population of Eastern Central Region of Portugal, attending a hospital outpatient clinic (ambulatory setting) for routine follow-up.</p> <p>Methods</p> <p>Medical data of all patients that attended at least two medical appointments of hypertension/dyslipidemia in a university hospital over a one and a half year period (from January 2008 to June 2009) were retrospectively analysed. Demographic variables, clinical data and blood pressure values of hypertensive patients included in the study, as well as prescribing metrics were examined on a descriptive basis and expressed as the mean ± SD, frequency and percentages. Student's test and Mann-Whitney rank sum test were used to compare continuous variables and χ²test and Fisher exact probability test were used to test for differences between categorical variables.</p> <p>Results</p> <p>In all, 37% of hypertensive patients (n = 76) had their blood pressure controlled according to international guidelines. About 45.5% of patients with a target blood pressure <140/90 mmHg (n = 156) were controlled, whereas in patients with diabetes or chronic kidney disease (n = 49) the corresponding figure was only 10.2% (<it>P </it>< 0.001). Among patients initiating hypertension/dyslipidemia consultation within the study period 32.1% had stage 2 hypertension in the first appointment, but this figure decreased to 3.6% in the last consultation (<it>P </it>= 0.012). Thiazide-type diuretics were the most prescribed antihypertensive drugs (67%) followed by angiotensin receptor blockers (60%) and beta-blockers (43%). About 95.9% patients with comorbid diabetes were treated with an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker.</p> <p>Conclusions</p> <p>Clinically important blood pressure decreases can be achieved soon after hypertension medical appointment initiation. However, many hypertensive patients prescribed with antihypertensive therapy fail to achieve blood pressure control in clinical practice, this control being worse among patients with diabetes or chronic kidney disease. As pharmacotherapy patterns seem to coincide with international guidelines, further research is needed to identify the causes of poor blood pressure control.</p

Left Ventricular Diastolic Function in Type 2 Diabetes Mellitus and the Association With Coronary Artery Calcium Score: A Cardiac MRI Study

OBJECTIVE: The purpose of this study was to compare cardiac MRI-derived parameters of left ventricular (LV) diastolic function between uncomplicated type 2 diabetes mellitus (DM2) and normoglycemic control subjects and to evaluate whether these parameters of LV diastolic function are related to coronary atherosclerosis. SUBJECTS AND METHODS: We prospectively studied 41 subjects with DM2 and 21 normoglycemic control subjects (30 women and 32 men; mean age, 57.2 ± 7.1 [SD] years) with no evidence of overt cardiovascular disease. We used cardiac MRI to measure LV volumes, LV peak filling rate (PFR), and transmitral flow and CT to determine coronary artery calcium scores. RESULTS: Absolute values of the peak filling rate (PFR) were significantly lower in DM2 patients than in control subjects (mean ± SD, 293.2 ± 51.7 vs 375.7 ± 102.8 mL/s, respectively; p < 0.001). Mitral peak E velocities (mean ± SD, 42.8 ± 10.7 vs 48.8 ± 10.4 cm/s; p = 0.040) and peak E velocity-to-peak A velocity ratios (0.88 ± 0.3 vs 1.1 ± 0.3; p = 0.002) were also lower in DM2 patients compared with control subjects. DM2 patients with coronary artery calcification showed a lower PFR normalized to stroke volume (SV) (mean ± SD, 4.4 ± 1.0 vs 5.3 ± 1.4, respectively; p = 0.038) and lower mitral peak E velocities (40.1 ± 11.3 vs 48.0 ± 7.3 cm/s; p = 0.024) than DM2 patients without coronary calcification. PFR normalized to SV was independently associated with the presence of coronary artery calcification (β = -1.5, p = 0.005). CONCLUSION: DM2 decreases cardiovascular MRI-derived parameters of LV diastolic function. Patients with DM2 and coronary atherosclerosis show a more impaired LV diastolic function than patients without coronary atherosclerosis

Comparative outcome assessment of epidermal growth factor receptor tyrosine kinase inhibitors for the treatment of advanced non-small-cell lung cancer: A network meta-analysis

Introduction: Tyrosine kinase inhibition of the epidermal growth factor receptor (EGFR) is the standard in the first line treatment of patients with advanced nonsmall- cell lung cancer (NSCLC) harbouring EGFR activating mutations. Here we aim to discern efficacy and toxicity measures through a meta-analysis of published studies that could aid treatment selection. Materials And Methods: We performed a meta-analysis of the main randomized clinical trials evaluating the currently approved EGFR-TKIs in first-line of treatment of EGFR-positive advanced NSCLC. Cochrane guidelines were used for statistical analysis. Results: 3,179 patients were included. All EGFR TKIs showed improved outcomes with respect to ORR and PFS when compared to standard platinum-doublet chemotherapy. Comparative ORR for gefitinib, erlotinib and afatinib were 52.1%, 67.3% and 61.6% respectively. HRs for PFS were 0.62 (95% CI, 0.38-1.00) for gefitinib, 0.28 (95% CI, 0.17-0.45) for erlotinib and 0.40 (95% CI, 0.20-0.83) for afatinib. HRs for OS were not statistically significant for any agent. Conclusions: Our results suggest similar clinical efficacy and higher toxicity of Afatinib treatment. As this still remains the agent with best CSF penetration, we suggest its use is limited to patients presenting with brain metastasis. We suggest the use of Gefitinib in patients without CNS involvement. Faced with the impossibility to dose-reduce Gefitinib, Erlotinib represents a tolerable and effective alternative to Afatinib and Gefitinib if response to EGFR inhibition is considered still effective.Logistic provision from the Cearense School of Oncology, Ceará Cancer Institute, Haroldo Juaçaba Hospital, Fortaleza, Ceará, Brazil, and The Clatterbridge Cancer Centre NHS Foundation Trust, Wirral & Liverpool, England, United Kingdom. RAM has received honoraria from Pfizer Advisory Board, Zodiac advisory board, AstraZeneca, Novartis, National Science Centre, Krakow, Poland, and educational grant from Pierre Fabre, Amgem. RAM is ad hoc consultant at Ministry of Health, Brasília, Brazil. The other authors have no conflicts of interest in this manuscript. GM has received honoraria from Bristol Myers Squibb, Roche and AstraZeneca

Perspective advices in the management of ovarian hyperstimulation syndrome

The increasing availability around the world of in vitro fertilization helps many patients who would be otherwise unable to conceive; however, this procedure has also some disadvantages

The non-coding snRNA 7SK controls transcriptional termination, poising, and bidirectionality in embryonic stem cells

BACKGROUND: Pluripotency is characterized by a unique transcriptional state, in which lineage-specification genes are poised for transcription upon exposure to appropriate stimuli, via a bivalency mechanism involving the simultaneous presence of activating and repressive methylation marks at promoter-associated histones. Recent evidence suggests that other mechanisms, such as RNA polymerase II pausing, might be operational in this process, but their regulation remains poorly understood. RESULTS: Here we identify the non-coding snRNA 7SK as a multifaceted regulator of transcription in embryonic stem cells. We find that 7SK represses a specific cohort of transcriptionally poised genes with bivalent or activating chromatin marks in these cells, suggesting a novel poising mechanism independent of Polycomb activity. Genome-wide analysis shows that 7SK also prevents transcription downstream of polyadenylation sites at several active genes, indicating that 7SK is required for normal transcriptional termination or control of 3′-UTR length. In addition, 7SK suppresses divergent upstream antisense transcription at more than 2,600 loci, including many that encode divergent long non-coding RNAs, a finding that implicates the 7SK snRNA in the control of transcriptional bidirectionality. CONCLUSIONS: Our study indicates that a single non-coding RNA, the snRNA 7SK, is a gatekeeper of transcriptional termination and bidirectional transcription in embryonic stem cells and mediates transcriptional poising through a mechanism independent of chromatin bivalency.GCB was funded by an EMBO Long-Term Post-Doctoral Fellowship and a Marie Curie Intra-European Fellowship for Career Development. PA was supported by a Royal Society Newton International Fellowship and a Corpus Christi College research fellowship. This work was supported by Cancer Research UK, European Research Council (Advanced Grant, TK), EMBL (PB) and Swedish Research Council (GCB)

Design and Implementation of a Collaborative Clinical Practice and Research Documentation System Using SNOMED-CT and HL7-CDA in the Context of a Pediatric Neurodevelopmental Unit

This paper introduces a prototype for clinical research documentation using the structured information model HL7 CDA and clinical terminology (SNOMED CT). The proposed solution was integrated with the current electronic health record system (EHR-S) and aimed to implement interoperability and structure information, and to create a collaborative platform between clinical and research teams. The framework also aims to overcome the limitations imposed by classical documentation strategies in real-time healthcare encounters that may require fast access to complex information. The solution was developed in the pediatric hospital (HP) of the University Hospital Center of Coimbra (CHUC), a national reference for neurodevelopmental disorders, particularly for autism spectrum disorder (ASD), which is very demanding in terms of longitudinal and cross-sectional data throughput. The platform uses a three-layer approach to reduce components’ dependencies and facilitate maintenance, scalability, and security. The system was validated in a real-life context of the neurodevelopmental and autism unit (UNDA) in the HP and assessed based on the functionalities model of EHR-S (EHR-S FM) regarding their successful implementation and comparison with state-of-the-art alternative platforms. A global approach to the clinical history of neurodevelopmental disorders was worked out, providing transparent healthcare data coding and structuring while preserving information quality. Thus, the platform enabled the development of user-defined structured templates and the creation of structured documents with standardized clinical terminology that can be used in many healthcare contexts. Moreover, storing structured data associated with healthcare encounters supports a longitudinal view of the patient’s healthcare data and health status over time, which is critical in routine and pediatric research contexts. Additionally, it enables queries on population statistics that are key to supporting the definition of local and global policies, whose importance was recently emphasized by the COVID pandemic.info:eu-repo/semantics/publishedVersio

Bilateral versus ipsilesional cortico-subcortical activity patterns in stroke show hemispheric dependence

Background Understanding of interhemispheric interactions in stroke patients during motor control is an important clinical neuroscience quest that may provide important clues for neurorehabilitation. In stroke patients, bilateral overactivation in both hemispheres has been interpreted as a poor prognostic indicator of functional recovery. In contrast, ipsilesional patterns have been linked with better motor outcomes. Aim We investigated the pathophysiology of hemispheric interactions during limb movement without and with contralateral restraint, to mimic the effects of constraint-induced movement therapy. We used neuroimaging to probe brain activity with such a movement-dependent interhemispheric modulation paradigm. Methods We used an fMRI block design during which the plegic/paretic upper limb was recruited/mobilized to perform unilateral arm elevation, as a function of presence versus absence of contralateral limb restriction ( n = 20, with balanced left/right lesion sites). Results Analysis of 10 right-hemispheric stroke participants yielded bilateral sensorimotor cortex activation in all movement phases in contrast with the unilateral dominance seen in the 10 left-hemispheric stroke participants. Superimposition of contralateral restriction led to a prominent shift from activation to deactivation response patterns, in particular in cortical and basal ganglia motor areas in right-hemispheric stroke. Left-hemispheric stroke was in general characterized by reduced activation patterns, even in the absence of restriction, which induced additional cortical silencing. Conclusion The observed hemispheric-dependent activation/deactivation shifts are novel and these pathophysiological observations suggest short-term neuroplasticity that may be useful for hemisphere-tailored neurorehabilitation.info:eu-repo/semantics/publishedVersio