ALEX test Dotaz Zobrazit nápovědu
Účel přehledu: Cílem tohoto článku je poskytnout stručný přehled modelů pro hodnocení rizika, které stratifikují hospitalizované nechirurgické pacienty s akutním onemocněním podle rizika žilního tromboembolismu (ŽTE). Nové poznatky: Modely pro hodnocení rizika (risk‑assessment models, RAM) u hospitalizovaných nechirurgických pacientů ohrožených rozvojem ŽTE vytvořené do roku 2005 se pokoušely identifikovat ohrožené pacienty s využitím bodového systému nebo systému odpovědí ano/ne na základě přítomnosti exponujících (akutní interní onemocnění) nebo predisponujících (genetické či klinické charakteristiky) rizikových faktorů pro rozvoj ŽTE. Tyto RAM byly odvozeny z údajů týkajících se převážně podskupin účastníků randomizovaných kontrolovaných studií; byly těžkopádné, neprošly přísnou validací a vycházely z omezených poznatků ohledně kvantitativní interakce zmíněných rizikových faktorů. Nedávno byly navrženy zjednodušené RAM pro uvedenou populaci pacientů. Zmíněné RAM jsou tvořeny různými bodovými systémy a prahovou hodnotou, na jejichž základě lze rozpoznat ohrožené skupiny nemocných, jimž by prospěla tromboprofylaxe. Některé z těchto bodových systémů byly sice odvozeny intuitivně, ovšem byly validovány – prospektivně či retrospektivně – u rozsáhlých kohort nemocných a vykazují dobrou senzitivitu. Zvýšené riziko rozvoje ŽTE během hospitalizace nebo v období po propuštění z nemocnice bylo v různých modelech shodně spojeno s přítomností malignity, s údajem o předchozí ŽTE v anamnéze s hyperkoagulabilitou, s pokročilým věkem a s imobilitou. Souhrn: Byla provedena validace jednoduchých RAM, které na základě uplatnění bodových systémů zahrnujících exponující či predisponující rizikové faktory předpovídají riziko rozvoje ŽTE u hospitalizovaných nechirurgických pacientů. Lze doufat, že tyto RAM mohou identifikovat akutně nemocné nechirurgické pacienty s dalšími charakteristikami, kteří jednoduše nezapadají do skupinově specifických kategorií hodnocení rizika rozvoje tromboembolie aktuálně navrhovaných mezinárodními klinickými doporučeními.
PURPOSE OF REVIEW: The aim is to provide a concise review of risk assessment models that stratify hospitalized acutely ill medical patients at risk of venous thromboembolism (VTE). RECENT FINDINGS: Risk-assessment models (RAMs) for hospitalized medical patients at risk for VTE prior to 2005 attempted to identify at-risk patients using a point system or binary yes/no approach as to the existence of exposing (acute medical illness) or predisposing (genetic or clinical characteristic) risk factors for VTE. These RAMs were derived from data predominately from patient subgroups within randomized controlled trials and were cumbersome, not subject to rigorous validation, and were based on limited evidence of how these risk factors interacted in a quantitative manner. Recently, simplified RAMs have been proposed that have included this patient group. The RAMs are composed of various point systems and a threshold, which then would identify at-risk patient groups that would benefit from thromboprophylaxis. Although some of the point systems have been derived intuitively, they have been validated in large patient cohorts either prospectively or retrospectively and have shown good sensitivity. The presence of malignancy, prior VTE, hypercoagulability, advanced age and immobility all conferred increased risk of VTE during hospitalization or in the posthospital discharge period in the various models. SUMMARY: Simple RAMs based on point systems to predict risk of VTE for the hospitalized medical patient have been validated that include either exposing or predisposing risk factors for VTE. It is hoped that these RAMs may identify acutely ill medical patients with additional characteristics that do not easily fit into group-specific thromboembolic risk assessment categories as currently proposed by international clinical guidelines.
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This study is aimed at proving the clinical benefit of the MELISA® test in the minimization or complete elimination of health problems in patients with confirmed hypersensitivity to metals used for tissue replacements. A group of 305 patients aged 20-75 years with previously proven metal hypersensitivity (initial MELISA® test), mainly to titanium and then to another fifteen metals, was chosen from the database at the Institute of Dental Medicine. From these patients, a final group of 42 patients agreed to participate in the study, 35 of which were female and 7 were male. The patients completed a special questionnaire aimed at information regarding change of health status from their last visit and determining whether the results of the initial MELISA® test and recommendations based on it were beneficial for patients or not. They were clinically examined, and peripheral blood samples were taken to perform follow-up MELISA® tests. Questionnaire data was processed, and the follow-up MELISA® test results were compared with the results of the initial MELISA® tests. For statistical analysis, the Fisher's exact test and paired T-test were used. Thirty-two patients reported that they followed the recommendations based on the results of the initial MELISA® tests, and of these, 30 patients (94%) confirmed significant health improvement. Six patients did not follow the recommendation, and from these, only one patient reported an improvement in his health problems. By comparison of the initial and follow-up MELISA® test results, it can be stated that the hypersensitivity to the given metal decreased or disappeared after the therapeutic interventions performed based on the initial MELISA® test results. The evaluation of the data obtained from patients in this study confirmed a significant clinical benefit of MELISA® test.
- MeSH
- alergie diagnóza MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- následné studie MeSH
- průzkumy a dotazníky * MeSH
- senioři MeSH
- titan škodlivé účinky MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
Clinical assessment and management of musculoskeletal conditions of different joints may be broken down into considerations of Pain, Alignment, Strength and Stability (PASS). In recent years these factors have allowed a systematic approach and has enabled the development in our understanding of clinical subgroups, which enable targeted or stratified care. This paper considers the use of the PASS concept to determine the most appropriate treatment and interventions, specifically when considering treatment of two common musculoskeletal conditions, patellofemoral pain and low back pain.
Mesenteric veins are more sensitive than arteries to the constrictor effects of sympathetic nerve stimulation and alpha-adrenoceptor agonists. We tested the hypothesis that alpha(1)- and alpha(2)-adrenoceptors interact to enhance adrenergic reactivity of mesenteric veins. We studied neurogenic and agonist-induced constrictions of mesenteric veins and arteries in vitro. Norepinephrine concentration-response curves were left-shifted in veins compared to arteries. UK 14,304 (0.01-1 microM, alpha(2)-adrenoceptor receptor agonist) did not constrict arteries or veins but enhanced constrictions and Ca(2+) signals mediated by alpha(1)-adrenoceptor stimulation in veins. Yohimbine (alpha(2)-adrenoceptor receptor antagonist) and MK912 (alpha(2C)-adrenoceptor receptor antagonist), but not alpha(2A)- or alpha(2B)-adrenoceptor antagonists, produced rightward shifts in norepinephrine concentration-response curves in veins. Pharmacological studies revealed that alpha(1D)-adrenoceptors mediate venous constrictions. Norepinephrine responses in veins from alpha(2C)-adrenoceptor knock-out (KO) mice were not different from wild type veins. Yohimbine inhibited norepinephrine constrictions in alpha(2C)-adrenoceptor KO veins suggesting that there is upregulation of other alpha(2)-adrenoceptors in alpha(2C)-KO mice. These data indicate that alpha(1D)- and alpha(2C)-adrenoceptors interact in veins but not in arteries. This interaction enhances venous adrenergic reactivity. Mesenteric vein-specific alpha(2)-adrenoceptor linked Ca(2+) and perhaps other signaling pathways account for enhanced venous adrenergic reactivity.
- MeSH
- alfa-1-adrenergní receptory - agonisté farmakologie MeSH
- alfa-1-adrenergní receptory metabolismus fyziologie MeSH
- alfa-2-adrenergní receptory - agonisté farmakologie MeSH
- alfa-2-adrenergní receptory - antagonisté farmakologie MeSH
- alfa-2-adrenergní receptory genetika metabolismus fyziologie MeSH
- arteriae mesentericae účinky léků fyziologie MeSH
- myši inbrední C57BL MeSH
- myši knockoutované MeSH
- myši MeSH
- noradrenalin fyziologie MeSH
- protein - isoformy antagonisté a inhibitory MeSH
- sympatický nervový systém účinky léků MeSH
- techniky in vitro MeSH
- vápníková signalizace účinky léků MeSH
- vazokonstrikce účinky léků MeSH
- vena mesenterica účinky léků fyziologie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- srovnávací studie MeSH
BACKGROUND: A 27-year-old man was referred to an oncology department following right orchiectomy for a stage I testicular seminoma at high risk for recurrence. He presented 6 weeks after the orchiectomy with an atrophic left testis, fatigue and a history of infertility. INVESTIGATIONS: Measurement of serum levels of urea, electrolytes, liver enzymes, bilirubin, human chorionic gonadotropin, alpha-fetoprotein, lactate dehydrogenase, testosterone and luteinizing hormone, full blood count, and left testicular biopsy. DIAGNOSIS: Tubular atrophy of the left testis with islands of intratubular germ cell neoplasia (ITGCN), and hypergonadotropic hypogonadism. MANAGEMENT: The patient received adjuvant chemotherapy as a single dose of carboplatin for the seminoma at high risk for recurrence, and testosterone replacement for the hypergonadotropic hypogonadism. Radiotherapy to the ITGCN-bearing solitary testis or a second orchiectomy was offered to prevent the progression of ITGCN into an invasive germ cell tumor. After exploring his options with regards to fertility treatment, the patient chose to undergo second orchiectomy with a subsequent, unsuccessful, attempt at sperm retrieval. At 20 months after diagnosis of his initial seminoma the patient showed no sign of recurrence.
- MeSH
- androgeny terapeutické užití MeSH
- antitumorózní látky terapeutické užití MeSH
- atrofie MeSH
- dospělí MeSH
- germinální a embryonální nádory patologie MeSH
- hypogonadismus diagnóza terapie MeSH
- karboplatina terapeutické užití MeSH
- lidé MeSH
- mnohočetné primární nádory patologie terapie MeSH
- orchiektomie MeSH
- semenotvorné kanálky patologie MeSH
- seminom chirurgie patologie MeSH
- testikulární nádory chirurgie patologie MeSH
- testis patologie chirurgie MeSH
- testosteron terapeutické užití MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Ascidians (tunicates; sea squirts) are marine animals which provide a source of diverse, bioactive natural products, and a model for toxicity screenings. Compounds isolated from ascidians comprise an approved anti-tumor drug and many others are potent drug leads. Furthermore, the use of invertebrate embryos for toxicological screening tests or analysis offers the possibility to image a large number of samples for high throughput screens. Ascidians are members of a sister clade to the vertebrates and make a vertebrate-like tadpole larva composed of less than 3000 cells in 18 hours. The neural complex of the ascidian larva is made of only 350 cells (of which 100 are neurons) and functional genomic studies have now uncovered numerous GRNs underpinning neural specification and differentiation. Numerous studies showed that brain formation in ascidians is sensitive to toxic insults especially from endocrine disruptors making them a suitable model to study neurodevelopmental defects. Modern techniques available for ascidians, including transgenic embryos where 3D time lapse imaging of GFPexpressing reporter constructs can be analyzed, now permit numerous end-points to be evaluated in order to test the specific mode of action of many compounds. This review summarizes the key evidence suggesting that ascidian embryos are a favorable embryological model to study neurodevelopmental toxicity of different compounds with molecular and cellular end-points. We predict that ascidians may become a significant source of marine blue biotechnologies in the 21st century.
- MeSH
- centrální nervový systém účinky léků MeSH
- embryo nesavčí účinky léků MeSH
- geneticky modifikovaná zvířata MeSH
- modely u zvířat * MeSH
- objevování léků metody MeSH
- preklinické hodnocení léčiv metody MeSH
- testy toxicity MeSH
- Urochordata účinky léků embryologie genetika MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
The development of an amorphous solid dispersion (ASD) is a promising strategy for improving the low bioavailability of many poorly water-soluble active pharmaceutical ingredients (APIs). The construction of a temperature-composition (T-C) phase diagram for an API-polymer combination is imperative as it can provide critical information that is essential for formulating stable ASDs. However, the currently followed differential scanning calorimetry (DSC)-based strategies for API solubility determination in a polymer at elevated temperatures are inefficient and, on occasions, unreliable, which may lead to an inaccurate prediction at lower temperatures of interest (i.e., T = 25 °C). Recently, we proposed a novel DSC-based protocol called the "step-wise dissolution" (S-WD) method, which is both cost- and time-effective. The objective of this study was to test the applicability of the S-WD method regarding expeditious verification of the purely-predicted API-polymer compatibility via the perturbed chain-statistical associating fluid theory (PC-SAFT) equation of state (EOS). Fifteen API-polymer T-C phase diagrams were reliably constructed, with three distinct API-polymer case types being identified regarding the approach used for the S-WD method. Overall, the PC-SAFT EOS provided satisfactory qualitative descriptions of the API-polymer compatibility, but not necessarily accurate quantitative predictions of the API solubility in the polymer at T = 25 °C. The S-WD method was subsequently modified and an optimal protocol was proposed, which can significantly reduce the required experimental effort.
OBJECTIVE: To evaluate the clinical and economic impact of adopting noninvasive prenatal testing (NIPT) using circulating cell-free DNA as a first-line screening method for trisomy 21, 18, and 13 in the general pregnancy population. METHODS: A decision-analytical model was developed to assess the impact of adopting NIPT as a primary screening test compared to conventional screening methods. The model takes the Belgium perspective and includes only the direct medical cost of screening, diagnosis, and procedure-related complications. NIPT costs are EUR 260. Clinical outcomes and the cost per trisomy detected were assessed. Sensitivity analysis measured the impact of NIPT false-positive rate (FPR) on modelled results. RESULTS: The cost per trisomy detected was EUR 63,016 for conventional screening versus EUR 66,633 for NIPT, with a difference of EUR 3,617. NIPT reduced unnecessary invasive tests by 94.8%, decreased procedure-related miscarriages by 90.8%, and increased trisomies detected by 29.1%. Increasing the FPR of NIPT (from < 0.01 to 1.0%) increased the average number of invasive procedures required to diagnose a trisomy from 2.2 to 4.5, respectively. CONCLUSION: NIPT first-line screening at a reasonable cost is cost-effective and provides better clinical outcomes. However, modelled results are dependent on the adoption of an NIPT with a low FPR.
