Searching for an optimal AUC estimation method: a never-ending task?

An effective method of construction of a linear estimator of AUC in the finite interval, optimal in the minimax sense, is developed and demonstrated for five PK models. The models may be given as an explicit C(t) relationship or defined by differential equations. For high variability and rich sampling the optimal method is only moderately advantageous over optimal trapezoid or standard numerical approaches (Gauss-Legendre or Clenshaw-Curtis quadratures). The difference between the optimal estimator and other methods becomes more pronounced with a decrease in sample size or decrease in the variability. The described estimation method may appear useful in development of limited-sampling strategies for AUC determination, as an alternative to the widely used regression-based approach. It is indicated that many alternative approaches are also possible. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10928-014-9392-y) contains supplementary material, which is available to authorized users

Patophysiology of atherosclerosis based on research on apoE-knockout mice and their usefulness in checking new antiatherosclerotic agents

Obecnie wiadomo, że miażdżyca jest chorobą o podłożu zapalnym. Długo brakowało jednoznacznego dowodu na istotny wpływ zapalenia na rozwój miażdżycy. Uzyskano go dzięki nowemu zwierzęcemu modelowi miażdżycy - myszy, u której zastosowano technikę celowania genowego (apoE-knockout mice). Kluczowym etapem rozwoju miażdżycy jest prezentacja limfocytom T antygenu przez komórki dendrytyczne. Antygenem tym może być fragment "strawionej" przez makrofag, utlenionej lipoproteiny o małej dogęstości (LDL), białko szoku cieplnego 60 (HSP60), β2 glikoproteina I lub fragmenty antygenów bakteryjnych. W wyniku oddziaływania tych komórek następuje odpowiedź immunologiczna typu T helper 1 (komórkowa) lub typu T helper 2 (humoralna). Obecnie uważa się, że odpowiedź typu Th1 i jej mediatory: interferon γ, czynnik martwicy nowotworów α, interleukina 1, interleukina 12 oraz interleukina 18 działają przyspieszająco na rozwój miażdżycy, podczas gdy odpowiedź typu Th2 i jej mediatory: interleukina 4, interleukina 5, interleukina 10 oraz interleukina 13 hamują rozwój miażdżycy. Koncepcja miażdżycy jako zapalenia ukształtowała się dopiero w ostatnich latach, lecz obecnie jej wartość jest niekwestionowana, co wiąże się z określonymi konsekwencjami terapeutycznymi. W ostatnich latach oczywiste stało się więc, że szlak produktów 5-lipooksygenazy może odgrywać istotną rolę patogenezie miażdżycy. Zaczęto rozważać leki przeciwleukotrienowe jako potencjalną terapię miażdżycy. W niniejszej pracy omówiono wyniki badań własnych przeprowadzonych na eksperymentalnym modelu miażdżycy: myszach z podwójnie wyłączonymi genami dla apolipoproteiny E oraz dla receptora LDL. Wykazano, że inhibitory białka aktywującego 5-lipooksygenazę (FLAP) oraz bloker receptora dla leukotrienów cysteinylowych zmniejszają miażdżycę u zmienionych genetycznie myszy.Although atherosclerosis was previously thought to be primarily a degenerative disease, it is now well ascertained that its pathogenesis is inflammatory. This review describes the history of the new atherogenetic concept, including the pivotal role of apoE-knockout mice in understanding the inflammatory background of atherosclerosis. The pivotal stage of atherogenesis is antigen presentation by macrophages to T lymphocytes. This antigen could be a fragment of oxidized LDL"digested" by macrophage, heat shock protein 60, β2 glycoprotein I, or fragments of bacterial antigens. During interaction between these cells, an immunological response of type T helper 1 (cellular) or T helper 2 (humoral) arises. Th1 response and its mediators: (IFN-γ, TNF-α, interleukin 1, interleukin 12, and interleukin 18) increase atherogenesis, whereas Th2 response and its mediators: (interleukin 4, interleukin 5, and interleukin 10) decrease the development of atherosclerosis. The concept of atherosclerosis as an inflammatory disease is quite fresh; however, it is already considered an undisputable achievement of science, bringing particular therapeutic consequences. Since inflammation plays an important role in atherogenesis, during recent years it has become apparent that the 5-lipoxygenase (5-LO) pathway may play an important role in modifying the pathogenesis of atherosclerosis. These data raised the possibility that antileukotriene drugs may be an effective treatment regimen in atherosclerosis. In fact, we have found that among apoE and LDLR-double knockout mice the inhibition of FLAP, as well as cysteinyl leukotriene receptor blockade, was able to significantly prevent the development of atherosclerosis in gene-targeted mice

Analysis of variability of concentrations of valproic acid (VPA) and its selected metabolites in the blood serum of patients treated with VPA and patients hospitalized because of VPA poisoning

Aim of the study: To compare the metabolic profile of valproic acid (VPA) in the studied groups of cases through an analysis of variability of concentrations of VPA with its selected metabolites (2-ene-VPA, 4-ene-VPA, 3-keto-VPA). Study material : Blood serum samples collected from 27 patients treated with VPA drugs in the Psychiatry Unit and in the Neurology and Cerebral Strokes Unit at the Ludwik Rydygier Provincial Specialist Hospital in Krakow, and blood serum samples collected from 26 patients hospitalized because of suspected acute VPA poisoning at the Toxicology Department, Chair of Toxicology and Environmental Diseases, Jagiellonian University Medical College in Krakow. Results and conclusions : The analysis of concentrations of VPA and its selected metabolites has shown that the metabolic profile of VPA determined in cases of acute poisoning is different from cases of VPA therapy. One of VPA’s metabolic pathways – the process of desaturation – is unchanged in acute poisoning and prevails over the process of -oxidation. The ingestion of toxic VPA doses results in an increased formation of 4-ene-VPA, proportional to an increase in VPA concentration. Acute VPA poisoning involves the saturation of VPA’s metabolic transformations at the stage of -oxidation. The process of oxidation of 2-ene-VPA to 3-keto-VPA is slowed down after the ingestion of toxic doses

Stent fracture after endovascular treatment patient with subclavian vein thrombosis – difficult diagnosis and complication of venous thoracic outlet syndrome

Subclavian vein thrombosis is relatively rare. It constitutes 4 to 10% of all cases of venous thrombosis and is often associated with compression or canniulation of the subclavian vein. We present the case of patient with Paget-Schroetter syndrome treated in our center for right subclavian vein thrombosis as a result of the venous thoracic outlet syndrome (VTOS). In the case described below, VTOS was unrecognized and the stent fracture following endovascular treatment led to a relapse of venous thrombosis. Secondary angioplasty and stenting with subclavian vein decompression was successfully made. The patient was regularly monitored throughout the following year and there was no relapse of clinical symptoms. Conclusions: in case of subclavian vein thrombosis decompression is a very important step in the management of VTOS. It prevents recurrence of thrombosis and potential complications

Pharmacokinetics of diclofenac sodium and papaverine hydrochloride after oral administration of tablets to rabbits

Non-compartmental pharmacokinetic analysis of diclofenac sodium (DIC) and papaverine hydrochloride (PAP) after oral administration of composed tablets to rabbits was developed. HPLC method for determination of DIC and PAP in rabbit plasma was developed and validated. Chromatographic separation of DIC, PAP and the IS was achieved on a Zorbax SB C18 5-μm column (150 mm ◊ 4.6 mm) using methanolwater (55 : 45, v/v) as mobile phase at a flow rate of 0.8 mL/min. Pharmacokinetic analysis showed that oral administration of a tablet composed of DIC and PAP do not change the pharmacokinetic parameters such as MRT, MAT, Cl and bioavailability of the active substances compared with single administration of DIC and PAP after single dose

Risk factors for surgical site infections in rectal cancer patients

Introduction. Rectal cancer surgery is associated with high rates of post-operative complications in which the most common are Surgical Site Infections (SSI). Materials and methods. Factors responsible for SSI incidence were retrospectively analysed in rectal cancer patients who had undergone surgery at a single centre for oncology between July 2012 and July 2016. The study end-point was patients’ contracting SSI. Statistical analyses were performed by the ‘Statistica 12’ package consisting of the Pearson’s Chi-squared test (χ2), the Kruskal-Wallis test and the Mann-Whitney U-test (with continuity correction). Qualitative variables were analysed using log-linear analysis. The likelihoods of SSI incidence were compared by using odds ratios within 95% confidence limits. Results. Amongst the 187 patient subjects under observation during their 30 day follow-up, 44 (23.5%) suffered from post-operative complications of which SSI were the most common at 27 (14.4%). In those patients with advanced stage IV cancer, SSI occurred 3-fold more compared to patients with lower stage cancers; respectively 27.3% vs 11.7%, p = 0.021. Multivariate analysis demonstrated that the highest SSI risk was in patients having a low-lying tumour (≤ 5 cm from the anal rim; OR 2.31 (95% CI of 1.15 to 4.62), p = 0.019 and those patients who had undergone Hartmann’s procedure; OR 1.85 (95% CI of 1.04 to 3.31), p = 0.038. Conclusions. Surgical site infections in rectal cancer patients undergoing surgery occur significantly more in those at advanced stage IV rectal cancer where the tumour is low-lying (0–5 cm from the anal rim) and after having undergone the Hartmann’s procedure

Simultaneous ipsilateral ring-stripping retrograde common carotid endarterectomy and standard carotid bifurcation endarterectomy

W pracy przedstawiono przypadek 71-letniego chorego, który został przyjęty do Kliniki Chirurgii Ogólnej w celu operacyjnego leczenia współistniejącego zwężenia tętnic szyjnych wewnętrznych z zamknięciem lewej tętnicy szyjnej wspólnej. U chorego wykonano arteriografię gałęzi łuku aorty i stwierdzono wstecznie zakontrastowany, drożny dystalny odcinek tętnicy szyjnej wspólnej i jej rozwidlenia. Śródoperacyjnie, po przeprowadzeniu arteriotomii tętnicy szyjnej wspólnej i ocenie blaszki miażdżycowej, wykonano wsteczne udrożnienie tętnicy szyjnej wspólnej lewej z jednoczasową standardową endarterektomią opuszki i tętnicy szyjnej wewnętrznej. W przebiegu pooperacyjnym nie zaobserwowano powikłań.We presented a case of a 71-year-old male patient admitted to the Department of Surgery because of bilateral stenoses of internal carotid arteries with simultaneous occlusion of left common carotid artery. The angiography of aortic arch branches was performed and demonstrated retrograde inflow of contrast medium into the patent distal part of common carotid and carotid bifurcation. During the operation after an arteriotomy of common carotid artery and evaluation of common carotid plaque the retrograde ring-stripping common carotid endarterectomy was performed with simultaneous standard endarterectomy of internal carotid artery and carotid bulb. No postoperative complications were observed

Pandemic changes in work, rest, physical activity and diet versus nutritional status of respondents

The aim of the study was to determine how the COVID-19 pandemic affected the nutritional status of the respondents through changes in work mode, physical activity and diet among residents of the Tarnów region. Material and methods. The study was conducted using the diagnostic survey method, and the tool was the author's questionnaire. The study was conducted in January-February 2022, using the Google Forms platform. In total, data were collected from 414 people. The questionnaires were filled out mostly by women (67.9% vs. 32.1%). The average age of respondents was 31.9 years (±13.52). Results. Those who worked remotely and in hybrid mode had the highest percentages declaring an increase in food intake during the COVID-19 pandemic (65.0% and 59.7%, respectively). The highest percentages of those who indicated a deterioration in the quality of their food intake were those who worked remotely (60.0%) and hybrid job (45.5%), while those who did not work were the group that most often among the others indicated an improvement in the quality of their food (23.4%). Respondents with remote and hybrid jobs were the most likely to report a reduction in their activity level (72.5% and 58.4%, respectively). Considering the BMI of those surveyed before the COVID-19 pandemic and now, there is an apparent decrease in the percentage of those with a normal BMI in favor of overweight and obesity. Conclusions. During the COVID-19 pandemic period, the percentages of overweight and obese people increased. People working remotely and in hybrid mode not only increased the amount of food they consumed, but also began to consume lower-quality products, as well as more often reporting reduced levels of physical activity