Objective: Nowadays, it is recognized in most modern hospital and public health systems an increasing concern to measure the quality of care. The quality of care can be focused on the characteristics of hospital production and the indicators of performance. The indicators of performance can permit, generally, to decrease complication rate, morbidity, mortality and costs of care. Therefore, one of the ways to optimize the quality of care is to use medical decision support system. Methods: The optimization of malaria’s treatment is based on an automatic extraction of a geographic information system database that can store and provide relevant information on malaria’s patient case of different regions. The method proposed is consisted of height main steps namely: specification of the case, indications or problems, actions or treatments strategies, estimative outcomes (benefit and risk), performance measure, decision, result and optimization.
Předmětem přehledné práce je posouzení pozice methotrexátu (MTX) v moderní strategii léčby aktivní revmatoidní artritidy. Je konstatováno, že MTX není používán v běžné klinické praxi adekvátně, a to ani co se týče frekvence, tak výšky dávek a možné formy podávání. Dle doporučení EULAR (Evropské ligy proti revmatismu) má být MTX vždy součástí první léčebné strategie. Může být také kotevním lékem, kdy se k němu při nedostatečném efektu přidávají další syntetické či biologické léky. V poslední době se ukázala jako výhodná kombinace MTX s glukokortikoidy při zahajování léčby časné revmatoidní artritidy. Jako iniciální dávkování se doporučuje 10 mg MTX týdně s rychlou titrací na 25–30 mg týdně. Při rychlé eskalaci dávky je možné docílit stavu nízké aktivity až u 40 % pacientů. MTX se podává vždy v kombinaci s kyselinou listovou. Problémem perorálního MTX je nekonstantní vstřebávání, a to především vyšších dávek než 15 mg týdně. Výhodné je proto přejít na subkutánní podávání MTX. Metaanalýza sedmi studií prokázala větší účinnost subkutánního MTX oproti perorálnímu. Při subkutánním podávání je také rychlejší nástup účinku. Bylo také prokázáno, že přechod na subkutánní MTX může snižovat potřebu biologické léčby až o 20 %, takže jde i o farmakoekonomicky výhodný postup. Subkutánní MTX je v současné době dostupný, přičemž výhodné jsou především autoinjektory ve formě předplněných per.
TThe aim of this review is to assess the position of methotrexate (MTX) in a modern strategy for the treatment of active rheumatoid arthritis. It has been noted that MTX is not used adequately in routine clinical practice, neither in frequency, dose and possible forms of administration. As recommended by EULAR (European League Against Rheumatism), MTX should always be part of the first treatment strategy. It can also be an anchor drug when other synthetic or biological drugs are added to MTX in case of inadequate response. More recently, the combination of MTX with glucocorticoids has been shown to be beneficial in initiating treatment for early rheumatoid arthritis. The dose of 10 mg MTX per week with rapid titration to 25–30 mg per week is recommended as an initial dose. With rapid dose escalation, up to 40% of patients can achieve low disease activity status. MTX is always given in combination with folic acid. The problem of oral MTX is non-constant absorption, especially at doses higher than 15 mg per week. It is, therefore, preferable to switch to subcutaneous administration of MTX. A meta-analysis of 7 studies showed greater efficacy of subcutaneous MTX than oral. Subcutaneous administration also results in a faster onset of action. It has also been shown that switching to subcutaneous MTX can reduce the need for biological treatment by up to 20%, making it a pharmacologically advantageous procedure. Subcutaneous MTX is currently available, with autoinjectors in the form of prefilled pens being particularly preferred.
- MeSH
- Injections, Subcutaneous MeSH
- Drug Therapy, Combination MeSH
- Humans MeSH
- Disease Management MeSH
- Methotrexate * administration & dosage pharmacology therapeutic use MeSH
- Arthritis, Rheumatoid * drug therapy MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
Spinocerebelámí ataxie byly dlouhou dobu skupinou syndromů definovaných na podkladě klinického obrazu. V posledních letech bylo dosaženo výrazného diagnostického pokroku identifikací řady molekulárních poruch, které jsou jejich příčinou. Očekává se, že možnosti molekulární genetiky vnesou do skupiny spinocerebelárních poruch jasnější řád a umožní identifikaci dalších klinických jednotek. V následující stati jsou shrnuty současné poznatky a názory na spinocerebelámí degenerace, diskutován optimální diagnostický postup vyšetření a krátce představeny nové klinické jednotky spolu s komentářem ohledně diferenciální diagnostiky v oblasti již déle známých metabolických pomch, které mohou obrazem spinocerebelámí ataxie začínat.
Spinocerebellar ataxia was for a long time a group of syndromes defined on the basis of the clinical picture. In recent years a marked diagnostic advance was achieved by identification of molecular disorders which are its cause. It is anticipated that molecular genetics will elucidate the group of spinocerebellar disorders and make it possible to identify further clinical units. In the presented article the authors summarize contemporary findings and views regarding spinocerebellar degeneration. discuss the optimal diagnostic procedure of examination and present briefly clinical units along with a commentary regarding the differential diagnosis in the sphere of metabolic disorders known for some time which may start by spinocerebellar ataxia.
- MeSH
- Diagnosis, Differential methods MeSH
- Genetic Diseases, Inborn diagnosis genetics pathology MeSH
- Classification MeSH
- Molecular Biology MeSH
- Gait Disorders, Neurologic diagnosis pathology MeSH
- Spinocerebellar Ataxias diagnosis genetics pathology MeSH
- Metabolism, Inborn Errors diagnosis pathology MeSH
- Publication type
- Review MeSH
The Differential Evolution (DE) is a widely used bioinspired optimization algorithm developed by Storn and Price. It is popular for its simplicity and robustness. This algorithm was primarily designed for real-valued problems and continuous functions, but several modified versions optimizing both integer and discrete-valued problems have been developed. The discrete-coded DE has been mostly used for combinatorial problems in a set of enumerative variants. However, the DE has a great potential in the spatial data analysis and pattern recognition. This paper formulates the problem as a search of a combination of distinct vertices which meet the specified conditions. It proposes a novel approach called the Multidimensional Discrete Differential Evolution (MDDE) applying the principle of the discrete-coded DE in discrete point clouds (PCs). The paper examines the local searching abilities of the MDDE and its convergence to the global optimum in the PCs. The multidimensional discrete vertices cannot be simply ordered to get a convenient course of the discrete data, which is crucial for good convergence of a population. A novel mutation operator utilizing linear ordering of spatial data based on the space filling curves is introduced. The algorithm is tested on several spatial datasets and optimization problems. The experiments show that the MDDE is an efficient and fast method for discrete optimizations in the multidimensional point clouds.
The survival and proliferation of cells and organisms require a highly coordinated allocation of cellular resources to ensure the efficient synthesis of cellular components. In particular, the total enzymatic capacity for cellular metabolism is limited by finite resources that are shared between all enzymes, such as cytosolic space, energy expenditure for amino-acid synthesis, or micro-nutrients. While extensive work has been done to study constrained optimization problems based only on stoichiometric information, mathematical results that characterize the optimal flux in kinetic metabolic networks are still scarce. Here, we study constrained enzyme allocation problems with general kinetics, using the theory of oriented matroids. We give a rigorous proof for the fact that optimal solutions of the non-linear optimization problem are elementary flux modes. This finding has significant consequences for our understanding of optimality in metabolic networks as well as for the identification of metabolic switches and the computation of optimal flux distributions in kinetic metabolic networks.
- MeSH
- Kinetics MeSH
- Metabolism * MeSH
- Models, Theoretical * MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
The CRISPR/Cas9 technique is widely used in experimentation with human cell lines as well as with other model systems, such as mice Mus musculus, zebrafish Danio reiro, and the fruit fly Drosophila melanogaster. However, publications describing the use of CRISPR/Cas9 for genome editing in non-model organisms, including non-model insects, are scarce. The introduction of this relatively new method presents many problems even for experienced researchers, especially with the lack of procedures to tackle issues concerning the efficiency of mutant generation. Here we present a protocol for efficient genome editing in the non-model insect species Pyrrhocoris apterus. We collected data from several independent trials that targeted several genes using the CRISPR/Cas9 system and determined that several crucial optimization steps led to a remarkably increased efficiency of mutant production. The main steps are as follows: the timing of embryo injection, the use of the heteroduplex mobility assay as a screening method, in vivo testing of sgRNA efficiency, and G0 germline mosaicism screening. The timing and the method of egg injections used here need to be optimized for other species, but other here-described optimization solutions can be applied immediately for genome editing in other insect species.
- Publication type
- Journal Article MeSH
Pozdní kožní porfyrie přichází ve své familiární formě s autosomálně dominantním způsobempřenosu defektu uroporfyrinogendekarboxylázy ve všech tkáních, nebo ve formě sporadické s tímtodefektem jen v játrech, s prevalencí v naší populaci v poměru přibližně 1:15 000. Etiologicky se najejím vzniku podílí přetížení organismu železem (způsobené často mutací genu hereditární hemochromatózy,HFE), chronická intoxikace alkoholem, dlouhodobá léčba estrogeny a infekce hepatitidouC. Spolehlivými terapeutickými metodami jsou sériové venepunkce a perorální léčba nízkýmidávkami chinolinových antimalarik, případně kombinace obou.Sdělení hovoří o faktorech a podmínkách vzniku nemoci a o mechanismech léčebného působeníobou uvedených metod. Zároveň uvádí na základě svých zkušeností návrh racionálního schématuoptimální terapie PCT.
Porphyria cutanea tarda appears in its familial form with an autosomal dominant transmissionof the defect of uroporphyrinogen decarboxylase in all tissues of the body, or in its sporadic formwith the defect in the liver only, in our population with a prevalence of 1:15.000. Etiologically thereparticipate in its appearance the iron overload (often caused by a mutation of the HFE gene ofhereditary hemochromatosis), chronic alcohol intoxication, long-term estrogen therapy, and hepatitisC infection. Reliable treatments are serial phlebotomies and oral therapy with low doses ofquinoline antimalarial drugs, or the combination of both.The report speaks of factors and conditions for the appearance of the disorder and of themechanisms of the therapeutic action of both the treatments. It also presents a draft of a rationalscheme for the optimal therapy of PCT.
- MeSH
- Antimalarials administration & dosage pharmacology therapeutic use MeSH
- Clinical Laboratory Techniques methods statistics & numerical data MeSH
- Porphyria Cutanea Tarda diagnosis etiology therapy MeSH
- Punctures MeSH
- Risk Factors MeSH
- Uroporphyrinogen Decarboxylase antagonists & inhibitors metabolism MeSH
- Iron metabolism MeSH
- Publication type
- Review MeSH
The article is devoted to a problem of replantation of extremity segments in different trauma mechanisms. While studying the outcomes of the replantation operations for full or partial amputation of limbs or their segments in the 495 patients (363 - men, 132 - women) the dependency on conditions and duration of their transportation, adequacy anti shock actions, anaesthetic provision, and correctional treatment after the operation is determined. Replantation and reconstructive operations were performed in 191 cases, of them in 7 - replantation of big segments. Simultaneous traumatic amputations of two and more segments were noted in 54 cases. Extended skin and soft tissue defects were found in 9 patients. Good outcomes were noted in 77.2% of cases. As Bogomolov and Sedov (2003) showed, a direct relationship was revealed between the anoxia period and the rate of arterial thrombosis.
- MeSH
- Anastomosis, Surgical MeSH
- Brachial Artery surgery MeSH
- Time Factors * MeSH
- Child MeSH
- Upper Extremity surgery MeSH
- Hypoxia complications MeSH
- Extremities surgery MeSH
- Blood Circulation MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Necrosis complications MeSH
- Postoperative Complications MeSH
- Child, Preschool MeSH
- Replantation * methods statistics & numerical data MeSH
- Retrospective Studies MeSH
- Amputation, Traumatic * surgery MeSH
- Fracture Fixation, Internal MeSH
- Check Tag
- Child MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Case Reports MeSH
Prenatální diagnostika a fetální terapie tvoří společně moderní obor zvaný fetální medicína. Smyslem prenatální diagnostiky je poskytnout úplné informace rodičovskému páru, zbavit neopodstatněných obav souvisejících s reprodukcí, umožnit aktivní plánování těhotenství, minimalizovat riziko narození postiženého dítěte a umožnit optimální a časnou postnatální léčbu plodu na základě stanovení včasné diagnózy. Prenatální vyšetření dělíme z pohledu plodu na neinvazivní (vyšetření z krve matky, ultrazvukové vyšetření) a invazivní (amniocentéza, biopsie choria, kordocentéza aj.). Vedle technických otázek fetální medicína vyvolává řadu specifických etických otázek. Můžeme považovat plod za pacienta s vlastními právy i když je součástí matčina těla? A pokud ano, může těhotná žena rozhodovat o veškerých aktivitách, které se budou týkat zejména plodu? Etické aspekty fetální medicíny jsou stejně významné jako vlastní techniky, kterými se jednotlivá vyšetření a invazivní zákroky provádějí. Skutečnost, že něco umíme a známe, nás ještě neospravedlňuje k tomu, abychom tuto praxi vykonávali, aniž si položíme základní otázku, zda naše profesionální činy jsou v souladu s etikou.
Prenatal diagnostic and fetal therapy form together a modern specialisation called a fetal medicine. A sense of prenatal diagnostic is to provide full information to parents, to relieve of fear concerning reproduction, to enable active pregnancy planning, to minimise a risk of handicapped child birth and to enable optimal and early postnatal treatment based on early diagnosis. Prenatal examinations can be divided into non-invasive (maternal blood tests, ultrasound) and invasive (amniocentesis, chorion biopsy, cordocentesis etc.). Besides technical aspects, recalls fetal medicine a number of specific ethical questions. Can we take fetus as a patient with its own privileges, although being a part of mother-s body? If so, can a pregnant woman make decisions of all activities especially concerning the fetus? Ethical aspects of fetal medicine are of the same importance, as individual examinations and invasive interventions techniques are. A fact, that we are qualified and have knowledge, does not justifies us to practice it, without giving a principal question, whether our professional behaviour complies with the ethics.
