Породы песчаники – редкие материалы высокой крепости – уникальные фрикционные материалы

Розглядаються питання при підготовці до відпрацювання пологих вугільних пластів на великих глибинах в умовах шахти «Довжанська Капітальна» ТОВ "ДТЕК Свердловантрацит". Проведено дослідження вміщуючих підготовчу виробку порід. Запропоновано можливості проектування комплексного видобутку супутніх корисних компонентів при підготовці Антрацитівського пластів до видобутку.The questions in preparation for mining of shallow coal seams at great depths in the mine "Dolzhanskaya Capital" LLC "DTEK Sverdlovantratsit." Investigations of host rocks of underground working. Suggested the possibility of designing an integrated co-production of useful components in preparation Antratsitovskogo of flat seam to production

Кооперативне законодавство УСРР 1920-х рр. комплексне історико-правове дослідження

Рецензія на книгу: Гладкий С.О. Кооперативне законодавство УСРР 1920-х років як явище правової реальності / С.О. Гладкий. – Полтава: РВВ ПУЕТ, 2010. – 522 с

6-thioguanine treatment in inflammatory bowel disease: A critical appraisal by a European 6-TG working party

Recently, the suggestion to use 6-thioguanine (6-TG) as an alternative thiopurine in patients with inflammatory bowel disease (IBD) has been discarded due to reports about possible (hepato) toxicity. During meetings arranged in Vienna and Prague in 2004, European experts applying 6-TG further on in IBD patients presented data on safety and efficacy of 6-TG. After thorough evaluation of its risk-benefit ratio, the group consented that 6-TG may still be considered as a rescue drug in stringently defined indications in IBD, albeit restricted to a clinical research setting. As a potential indication for administering 6-TG, we delineated the requirement for maintenance therapy as well as intolerance and/or resistance to aminosalicylates, azathioprine, 6-mercaptopurine, methotrexate and infliximab. Furthermore, indications are preferred in which surgery is thought to be inappropriate. The standard 6-TG dosage should not exceed 25 mg daily. Routine laboratory controls are mandatory in short intervals. Liver biopsies should be performed after 6-12 months, three years and then three-yearly accompanied by gastroduodenoscopy, to monitor for potential hepatotoxicity, including nodular regenerative hyperplasia (NRH) and veno-occlusive disease (VOD). Treatment with 6-TG must be discontinued in case of overt or histologically proven hepatotoxicity. Copyright (c) 2006 S. Karger AG, Basel

A Systematic Evaluation of Cost-Saving Dosing Regimens for Therapeutic Antibodies and Antibody-Drug Conjugates for the Treatment of Lung Cancer

Background: Expensive novel anticancer drugs put a serious strain on healthcare budgets, and the associated drug expenses limit access to life-saving treatments worldwide. Objective: We aimed to develop alternative dosing regimens to reduce drug expenses. Methods: We developed alternative dosing regimens for the following monoclonal antibodies used for the treatment of lung cancer: amivantamab, atezolizumab, bevacizumab, durvalumab, ipilimumab, nivolumab, pembrolizumab, and ramucirumab; and for the antibody-drug conjugate trastuzumab deruxtecan. The alternative dosing regimens were developed by means of modeling and simulation based on the population pharmacokinetic models developed by the license holders. They were based on weight bands and the administration of complete vials to limit drug wastage. The resulting dosing regimens were developed to comply with criteria used by regulatory authorities for in silico dose development. Results: We found that alternative dosing regimens could result in cost savings that range from 11 to 28%, and lead to equivalent pharmacokinetic exposure with no relevant increases in variability in exposure. Conclusions: Dosing regimens based on weight bands and the use of complete vials to reduce drug wastage result in less expenses while maintaining equivalent exposure. The level of evidence of our proposal is the same as accepted by regulatory authorities for the approval of alternative dosing regimens of other monoclonal antibodies in oncology. The proposed alternative dosing regimens can, therefore, be directly implemented in clinical practice.</p

Medication screening using Beers and STOPP/START criteria for elderly patients: Association between potentially inappropriate medication and medication-related hospital admissions

OBJECTIVE To assess the risk of medication-related hospital admissions associated with inappropriate medication use applying the Beers and the STOPP/START criteria. There are multiple screening methods to detect and reduce potentially inappropriate medication [PIM] and prescribing omissions (PPOs). Whether this will result in less medication-related hospitalisations is unknown. DESIGN A nested case-control study was conducted with a subset of patients of the Hospital Admissions Related to Medication (HARM) study. METHODS Cases were defined as patients ≥65 years with a potentially preventable medication-related hospital admission. For each case one control was selected, matched on age and sex. The primary determinant was defined as the presence of one or more PlMs and/or PPOs according to the Beers 2012 and the STOPP/START criteria. The strength of the association between a PIM/PPO and a medication-related hospital admission was evaluated with multivariate logistic regression and expressed as odds ratios with 95% confidence intervals (Cl95). RESULTS PlMs and PPOs detected with the STOPP/START criteria are associated with medication-related hospital admissions [OR 3.47; CI95 1.70-7.09], while for the presence of PIMs according to the Beers 2012 criteria a non-significant trend was visible (ORadj 1.49; CI95 0.90-2.47). CONCLUSION Both the STOPP/START criteria and the Beers 2012 criteria can be used to identify older people at risk for medication-related problems. The choice which set of criteria should be used is more dependent on other factors (e.g. national guidelines, practical considerations) than on the association of each set with ADR-related hospital admission

Pharmacogenetics in clinical practice

The availability of data from pharmacogenetic studies is reflected in therapeutic practice, and pharmacogenetics is slowly entering the medical arena. Preconditions for the utilisation of pharmacogenetic knowledge are that: 1) genetic variation and prevalence are known 2) pharmacological consequences (concerning efficacy or toxicity) are known 3) clinical relevance is demonstrated 4) data from pharmacogenetic studies are translated in to practical guidelines 5) knowledge and techniques are available. Tasks and responsibilities should be clearly set out regarding the request for pharmacogenetic analysis, the pharmacogenetic analysis itself, interpretation of the results and advice to the medical practitioner. The advice to give or not to give a drug to a patient, or to adjust drug dose or frequency, cannot be based exclusively on someone's genotype, but is the result of several factors. These include age, sex, weight, liver and renal function, concomitant medication, drug blood levels, serum albumin and protein binding, whether the patient smokes, nutrition and genetic factors (a combination of several genotypes). Pharmacogenetics will be an important and useful tool for individualising pharmacotherapy in the near future, as is therapeutic drug monitoring at present. The first examples of pharmacogenetic knowledge in medical practice are already in use

De prevalentie van incorrecte anti-Xa-bloedspiegels bij patiënten met een verminderde nierfunctie die laag-moleculairgewicht-heparines gebruiken

OBJECTIVE: To determine the prevalence of incorrect anti-Xa activity in patients with renal insufficiency after three days of therapeutic use of nadroparin, as advised in the guideline of the Dutch federation of Nephrology. DESIGN: Prospective, observational study. METHODS: The source population consisted of patients aged ≥18 years old with renal insufficiency (eGFR [MDRD] < 60 mL/min/1.73 m2) from the Jeroen Bosch hospital who were treated therapeutically with nadroparin. All patients were followed from the start of nadroparin use (index date) for three days. At day three (t=3) the anti-Xa activity was monitored. Weight, eGFR [MDRD] and nadroparin use during the three days were obtained from the electronic patient file. We also checked if the patients received a dose of nadroparin according to the guideline during the three days of use. RESULTS: In total 15 patients were included. Nadroparin dose was not adjusted according to the guideline in 13 patients. 4 of these patients (31%) still had a correct anti-Xa activity at t=3 and 9 had an incorrect anti-Xa activity. Only 2 patients received a nadroparin dose according to the guideline but had an incorrect anti-Xa activity at t=3. CONCLUSION: The results of this study suggest that therapeutic use of nadroparin with and without dose adjustment often leads to incorrect anti-Xa activity in patients with renal insufficiency. Therefore we advise to individualise nadroparin dose according to the first anti-Xa activity which is measured at day three of nadroparin use. To confirm this conclusion, additional research with more patients is needed