Prescrição Inapropriada em Idosos numa Enfermaria de Medicina Interna

INTRODUCTION: Polypharmacy is often observed in elderly patients and is associated with an increased risk of adverse drug reactions, side effects and interactions. Clinicians should be alert to inappropriate drug prescribing and reduce polypharmacy. MATERIAL AND METHODS: Observational, longitudinal, retrospective and descriptive study in an internal medicine ward in a Portuguese hospital. Polypharmacy was defined as the use of five or more different medicines. The purpose of this study was to describe the prevalence of polypharmacy and inappropriate prescribing at admission and discharge in an internal medicine ward, according to deprescribing.org guidelines/algorithms. A total of 838 consecutive patients were admitted between January and July 2017. All patients were aged under 65 years old, and those who died before discharge were excluded. Patients' medications were reviewed from a medical database at hospital admission and discharge. We examined whether patients were taking anticoagulants, proton pump inhibitors, benzodiazepines, antipsychotics and/or antihyperglycemic medication. RESULTS: A total of 483 patients were included, mean age was 79.2 ± 8.0 years, and 42% of patients were male. Median number of medications at admission and discharge was six. Polypharmacy was present in more than 70% of admitted patients. Proton pump inhibitors were the most common inappropriate prescription at discharge (17.2%). DISCUSSION: This study demonstrated a low use of inappropriate medicine (11.2% - 17.2%) in older people discharged from hospital, when compared to other studies. CONCLUSION: Our study shows that polypharmacy is present in more than 70% of elderly admitted patients. Nevertheless, the drug inappropriateness rate was not significantly affected by polypharmacy at both admission and discharge, being overall lower than published data.Introdução: A polimedicação é observada nos doentes idosos e está associada a um maior risco de reações adversas, efeitos secundários e interações. Os clínicos devem atentos à prescrição inapropriada e à redução da polimedicação. Material e Métodos: Estudo observacional, longitudinal, retrospetivo e descritivo, realizado numa enfermaria de medicina interna num hospital português. Definimos a polimedicação como o uso de cinco ou mais medicamentos. O objetivo foi descrever a prevalência da polimedicação e a prescrição inapropriada, na admissão e alta, de acordo com as guidelines/algoritmos definidos em deprescribing. org. Admitimos 838 doentes entre janeiro e julho de 2017. Excluímos todos aqueles com idade inferior a 65 anos e óbitos. A medicação dos doentes foi revista a partir da base de dados hospitalar, à admissão e à data de alta. Examinámos se os doentes estavam a tomar anticoagulantes, inibidores da bomba de protões, benzodiazepinas, antipsicóticos e/ou anti hiperglicémicos. Resultados: Incluímos 483 doentes, com média de idade de 79,2 ± 8,0 anos, e 42% dos quais eram homens. A mediana da medicação à admissão e à alta foi seis. A polimedicação estava presente em mais de 70% dos doentes admitidos. Os inibidores da bomba de protões foram a classe mais inapropriadamente prescrita à data de alta (17,2%). Discussão: Demonstrámos um uso reduzido de fármacos inapropriados (11,2% - 17,2%) nos idosos, à alta hospitalar, quando comparado com outros estudos. Conclusão: Demonstrámos que a polimedicação estava presente em mais de 70% dos idosos admitidos. Contudo, a taxa de prescrição inapropriada não afetou significativamente a polimedicação na admissão e na alta, sendo inferior aos dados publicados.info:eu-repo/semantics/publishedVersio

Towards automated test and validation of SIP solutions

IP networks are currently the major communication infrastructure used by an increasing number of applications and heterogeneous services, including voice services. In this context, the Session Initiation Protocol (SIP) is a signaling protocol widely used for controlling multimedia communication sessions such as voice or video calls over IP networks, thus performing vital functions in an extensive set of public and enter- prise solutions. However, the SIP protocol dissemination also entails some challenges, such as the complexity associated with the testing/validation processes of IMS/SIP networks. As a consequence, manual IMS/SIP testing solutions are inherently costly and time consuming tasks, being crucial to develop automated approaches in this specific area. In this perspective, this article presents an experimental approach for automated testing/validation of SIP scenarios in IMS networks. For that purpose, an automation framework is proposed allowing to replicate the configuration of SIP equipment from the pro- duction network and submit such equipment to a battery of tests in the testing network. The proposed solution allows to drastically reduce the test and validation times when compared with traditional manual approaches, also allowing to enhance testing reliability and coverage. The automation framework comprises of some freely available tools which are conveniently integrated with other specific modules implemented within the context of this work. In order to illustrate the advantages of the proposed automated framework, a real case study taken from a PT Inovação customer is presented comparing the time required to perform a manual SIP testing approach with the one time required when using the proposed auto- mated framework. The presented results clearly corroborate the advantages of using the presented framework.This work has been supported by FCT - Fundação para a Ciência e Tecnologia within the Project Scope: PEstOE/EEI/UI0319/2014. This research work was developed within the collaboration of PT Inovação (http://www.ptinovacao.pt/ en/)

Expression profiling on soybean leaves reveals integration of ER- and osmotic-stress pathways

Despite the potential of the endoplasmic reticulum (ER) stress response to accommodate adaptive pathways, its integration with other environmental-induced responses is poorly understood in plants. We have previously demonstrated that the ER-stress sensor binding protein (BiP) from soybean exhibits an unusual response to drought. The members of the soybean BiP gene family are differentially regulated by osmotic stress and soybean BiP confers tolerance to drought. While these results may reflect crosstalk between the osmotic and ER-stress signaling pathways, the lack of mutants, transcriptional response profiles to stresses and genome sequence information of this relevant crop has limited our attempts to identify integrated networks between osmotic and ER stress-induced adaptive responses. As a fundamental step towards this goal, we performed global expression profiling on soybean leaves exposed to polyethylene glycol treatment (osmotic stress) or to ER stress inducers. The up-regulated stress-specific changes unmasked the major branches of the ER-stress response, which include enhancing protein folding and degradation in the ER, as well as specific osmotically regulated changes linked to cellular responses induced by dehydration. However, a small proportion (5.5%) of total up-regulated genes represented a shared response that seemed to integrate the two signaling pathways. These co-regulated genes were considered downstream targets based on similar induction kinetics and a synergistic response to the combination of osmotic- and ER-stress-inducing treatments. Genes in this integrated pathway with the strongest synergistic induction encoded proteins with diverse roles, such as plant-specific development and cell death (DCD) domain-containing proteins, an ubiquitin-associated (UBA) protein homolog and NAC domain-containing proteins. This integrated pathway diverged further from characterized specific branches of ER-stress as downstream targets were inversely regulated by osmotic stress. The present ER-stress- and osmotic-stress-induced transcriptional studies demonstrate a clear predominance of stimulus-specific positive changes over shared responses on soybean leaves. This scenario indicates that polyethylene glycol (PEG)-induced cellular dehydration and ER stress elicited very different up-regulated responses within a 10-h stress treatment regime. In addition to identifying ER-stress and osmotic-stress-specific responses in soybean (Glycine max), our global expression-profiling analyses provided a list of candidate regulatory components, which may integrate the osmotic-stress and ER-stress signaling pathways in plants

The NAC domain-containing protein, GmNAC6, is a downstream component of the ER stress- and osmotic stress-induced NRP-mediated cell-death signaling pathway

<p>Abstract</p> <p>Background</p> <p>The endoplasmic reticulum (ER) is a major signaling organelle, which integrates a variety of responses against physiological stresses. In plants, one such stress-integrating response is the N-rich protein (NRP)-mediated cell death signaling pathway, which is synergistically activated by combined ER stress and osmotic stress signals. Despite the potential of this integrated signaling to protect plant cells against different stress conditions, mechanistic knowledge of the pathway is lacking, and downstream components have yet to be identified.</p> <p>Results</p> <p>In the present investigation, we discovered an NAC domain-containing protein from soybean, GmNAC6 (<it>Glycine max </it>NAC6), to be a downstream component of the integrated pathway. Similar to <it>NRP-A </it>and <it>NRP-B, GmNAC6 </it>is induced by ER stress and osmotic stress individually, but requires both signals for full activation. Transient expression of <it>GmNAC6 </it>promoted cell death and hypersensitive-like responses <it>in planta</it>. <it>GmNAC6 </it>and <it>NRPs </it>also share overlapping responses to biotic signals, but the induction of <it>NRPs </it>peaked before the increased accumulation of GmNAC6 transcripts. Consistent with the delayed kinetics of <it>GmNAC6 </it>induction, increased levels of <it>NRP-A </it>and <it>NRP-B </it>transcripts induced promoter activation and the expression of the <it>GmNAC6 </it>gene.</p> <p>Conclusions</p> <p>Collectively, our results biochemically link GmNAC6 to the ER stress- and osmotic stress-integrating cell death response and show that GmNAC6 may act downstream of the NRPs.</p

Hypoglycemia in elderly diabetic patients: experience in a diabetes unit

Introdução: Assiste-se atualmente a uma evolução paralela do envelhecimento da população e da prevalência crescente de Diabetes Mellitus. Os indivíduos idosos estão particularmente susceptíveis à ocorrência de episódios de hipoglicemia, responsáveis por uma morbimortalidade significativa nesta população. Os objetivos do estudo foram a avaliação da incidência de doentes diabéticos com episódios de hipoglicemia na população de idosos seguidos na Unidade Integrada de Diabetes (UID) do HFF e caracterizar, comparativamente, a população de idosos com e sem episódios de hipoglicemia. Materiais e métodos: Estudo observacional, longitudinal, retrospetivo, descritivo, consistindo na análise de variáveis demográficas, clínicas e laboratoriais constantes em processo clínico informático Soarian®, num período de um ano, procedendo-se a análise estatística dos mesmos. Resultados: Em 2013 mais de metade dos doentes seguidos na UID eram idosos, tendo-se verificado episódios de hipoglicemia em 22,6%. A maioria dos doentes com episódios de hipoglicemia (CH) tratava-se de doentes com mais de 75 anos e tinha um tempo de evolução de doença superior a 5 anos, com uma média de tempo de evolução de 17,5 anos. A presença de complicações microvasculares foi objetivada em mais de metade destes doentes (51,2%) sendo que 47,8% apresentavam complicações macrovasculares. A HbA1C média era de 7,8%, tendo apresentado, ao longo do ano, uma descida média de 0,6%. A maioria (71,7%) dos doentes CH estava medicado com insulina, mais de metade destes (54,3%) medicados com insulina com pico de ação, tratando-se de proporções significativamente superiores às objetivadas nos doentes sem episódios de hipoglicemia (SH). Relativamente ao uso de antidiabéticos orais, 26,1% estavam medicados com sulfonilureias. Conclusão: Este estudo vem reiterar a necessidade de individualização e adequação de objetivos de cuidados na população idosa e com mais comorbilidades, assumindo alvos glicémicos mais permissivos e esquemas terapêuticos com menor risco associado de hipoglicemia.info:eu-repo/semantics/publishedVersio

Fractional variational calculus of variable order

We study the fundamental problem of the calculus of variations with variable order fractional operators. Fractional integrals are considered in the sense of Riemann-Liouville while derivatives are of Caputo type.Comment: Submitted 26-Sept-2011; accepted 18-Oct-2011; withdrawn by the authors 21-Dec-2011; resubmitted 27-Dec-2011; revised 20-March-2012; accepted 13-April-2012; to 'Advances in Harmonic Analysis and Operator Theory', The Stefan Samko Anniversary Volume (Eds: A. Almeida, L. Castro, F.-O. Speck), Operator Theory: Advances and Applications, Birkh\"auser Verlag (http://www.springer.com/series/4850

OPE for Super Loops

We extend the Operator Product Expansion for Null Polygon Wilson loops to the Mason-Skinner-Caron-Huot super loop, dual to non MHV gluon amplitudes. We explain how the known tree level amplitudes can be promoted into an infinite amount of data at any loop order in the OPE picture. As an application, we re-derive all one loop NMHV six gluon amplitudes by promoting their tree level expressions. We also present some new all loops predictions for these amplitudes.Comment: 16 pages + appendices; 5 figure

Antimalarial Exposure Delays Plasmodium falciparum Intra-Erythrocytic Cycle and Drives Drug Transporter Genes Expression

BACKGROUND: Multi-drug resistant Plasmodium falciparum is a major obstacle to malaria control and is emerging as a complex phenomenon. Mechanisms of drug evasion based on the intracellular extrusion of the drug and/or modification of target proteins have been described. However, cellular mechanisms related with metabolic activity have also been seen in eukaryotic systems, e.g. cancer cells. Recent observations suggest that such mechanism may occur in P. falciparum. METHODOLOGY/PRINCIPAL FINDINGS: We therefore investigated the effect of mefloquine exposure on the cell cycle of three P. falciparum clones (3D7, FCB, W2) with different drug susceptibilities, while investigating in parallel the expression of four genes coding for confirmed and putative drug transporters (pfcrt, pfmdr1, pfmrp1 and pfmrp2). Mefloquine induced a previously not described dose and clone dependent delay in the intra-erythrocytic cycle of the parasite. Drug impact on cell cycle progression and gene expression was then merged using a non-linear regression model to determine specific drug driven expression. This revealed a mild, but significant, mefloquine driven gene induction up to 1.5 fold. CONCLUSIONS/SIGNIFICANCE: Both cell cycle delay and induced gene expression represent potentially important mechanisms for parasites to escape the effect of the antimalarial drug

Protection of rat renal vitamin E levels by ischemic-preconditioning

BACKGROUND: During renal transplantation, the kidney remains without blood flow for a period of time. The following reperfusion of this ischemic kidney causes functional and structural injury. Formation of oxygen-derived free radicals (OFR) and subsequent lipid peroxidation (LP) has been implicated as the causative factors of these injuries. Vitamin E is known to be the main endogenous antioxidant that stabilizes cell membranes by interfering with LP. The present study was designed to examine the role of ischemic-preconditioning (repeated brief periods of ischemia, IPC) in prevention of renal injury caused by ischemia-reperfusion (IR) in rats. METHODS: IPC included sequential clamping of the right renal artery for 5 min and release of the clamp for another 5 min for a 3 cycles. IR was induced by 30 min ischemia followed by 10 min reperfusion. Four groups of male rats were used: Control, IPC, IR and IPC-IR. Vitamin E, an endogenous antioxidant and as an index of LP, was measured by HPLC and UV detection in renal venous plasma and tissue. Renal function was assessed by serum creatinine and BUN levels. Renal damage was assessed in sections stained with Haematoxylin and Eosin. RESULTS: In the IR group, there was a significant decrease in vitamin E in plasma and tissue compared to a control group (p,0.05). In the IPC-IR group, vitamin E concentration was significantly higher than in the IR group (p,0.01). The results showed that 30 min ischemia in the IR group significantly (p,0.05) reduced renal function demonstrated by an increase in serum creatinine levels as compared with the control group. These results in the IPC group also showed a significant difference with the IR group but no significant difference in serum BUN and creatinine between IR and IPC-IR group were detected. Histological evaluation showed no structural damage in the IPC group and an improvement in the IPC-IR group compared to IR alone. CONCLUSIONS: In this study, IPC preserved vitamin E levels, but it could not markedly improve renal function in the early phase (1–2 h) of reperfusion. IPC may be a useful method for antioxidant preservation in organ transplantation

Novel Polymorphisms in Plasmodium falciparum ABC Transporter Genes Are Associated with Major ACT Antimalarial Drug Resistance

Chemotherapy is a critical component of malaria control. However, the most deadly malaria pathogen, Plasmodium falciparum, has repeatedly mounted resistance against a series of antimalarial drugs used in the last decades. Southeast Asia is an epicenter of emerging antimalarial drug resistance, including recent resistance to the artemisinins, the core component of all recommended antimalarial combination therapies. Alterations in the parasitic membrane proteins Pgh-1, PfCRT and PfMRP1 are believed to be major contributors to resistance through decreasing intracellular drug accumulation. The pfcrt, pfmdr1 and pfmrp1 genes were sequenced from a set of P.falciparum field isolates from the Thai-Myanmar border. In vitro drug susceptibility to artemisinin, dihydroartemisinin, mefloquine and lumefantrine were assessed. Positive correlations were seen between the in vitro susceptibility responses to artemisinin and dihydroartemisinin and the responses to the arylamino-alcohol quinolines lumefantrine and mefloquine. The previously unstudied pfmdr1 F1226Y and pfmrp1 F1390I SNPs were associated significantly with artemisinin, mefloquine and lumefantrine in vitro susceptibility. A variation in pfmdr1 gene copy number was also associated with parasite drug susceptibility of artemisinin, mefloquine and lumefantrine. Our work unveils new candidate markers of P. falciparum multidrug resistance in vitro, while contributing to the understanding of subjacent genetic complexity, essential for future evidence-based drug policy decisions