Jurnal Fakultas Ekonomi UM Metro (Universitas Muhammadiyah)
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Economic Evaluations of Pharmacogenetic and Pharmacogenomic Screening Tests:A Systematic Review. Second Update of the Literature
No full textObjectiveDue to extended application of pharmacogenetic and pharmacogenomic screening (PGx) tests it is important to assess whether they provide good value for money. This review provides an update of the literature.MethodsA literature search was performed in PubMed and papers published between August 2010 and September 2014, investigating the cost-effectiveness of PGx screening tests, were included. Papers from 2000 until July 2010 were included via two previous systematic reviews. Studies' overall quality was assessed with the Quality of Health Economic Studies (QHES) instrument.ResultsWe found 38 studies, which combined with the previous 42 studies resulted in a total of 80 included studies. An average QHES score of 76 was found. Since 2010, more studies were funded by pharmaceutical companies. Most recent studies performed cost-utility analysis, univariate and probabilistic sensitivity analyses, and discussed limitations of their economic evaluations. Most studies indicated favorable cost-effectiveness. Majority of evaluations did not provide information regarding the intrinsic value of the PGx test. There were considerable differences in the costs for PGx testing. Reporting of the direction and magnitude of bias on the cost-effectiveness estimates as well as motivation for the chosen economic model and perspective were frequently missing.ConclusionsApplication of PGx tests was mostly found to be a cost-effective or cost-saving strategy. We found that only the minority of recent pharmacoeconomic evaluations assessed the intrinsic value of the PGx tests. There was an increase in the number of studies and in the reporting of quality associated characteristics. To improve future evaluations, scenario analysis including a broad range of PGx tests costs and equal costs of comparator drugs to assess the intrinsic value of the PGx tests, are recommended. In addition, robust clinical evidence regarding PGx tests' efficacy remains of utmost importance.</p
Philosophy of quantum probability:An empiricist study of its formalism and logic
No full textHet gebruik van kansrekening is wijdverspreid in ons dagelijks leven (kansspelen, beleggingen en dergelijke) alsook in wetenschappelijke theorieën (genetica, statistische thermodynamica). In vrijwel alle gevallen kunnen relevante berekeningen voltrokken worden binnen het raamwerk van de klassieke kanstheorie gebaseerd op de axioma’s van Kolmogorov. Een bijzondere uitzondering wordt gegeven door de quantummechanica: de natuurkundige theorie die materie op atomaire schaal beschrijft. Zij geeft aanleiding tot een nieuwe kanstheorie: de quantumkanstheorie. Dit proefschrift behandelt de vraag hoe dit formalisme begrepen kan worden vanuit een filosofisch en fysisch perspectief.Het proefschrift is opgedeeld in drie delen. In het eerste deel worden het formalisme van de quantumkanstheorie en haar relatie tot de quantummechanica uiteengezet. In het tweede deel wordt gekeken naar de mogelijkheid om quantumkanstheorie te herformuleren zodat het past binnen het raamwerk van de axioma’s van Kolmogorov. Wiskundig valt deze mogelijkheid grotendeels samen met de mogelijkheid van het bestaan van verborgen variabelen theorieën voor de quantummechanica: theorieën die pogen fundamentele problemen in de quantummechanica op te lossen door additionele fysische eigenschappen aan systemen toe te kennen. De conclusie van deze onderzoeking is dat, hoewel klassieke herformuleringen van de quantumkanstheorie formeel mogelijk zijn, zij weinig inzicht bieden in het formalisme van de quantumkanstheorie zelf. In het derde deel wordt een directere onderzoeking van de quantumkanstheorie ondernomen. Een herformulering van de quantumkanstheorie wordt verkregen door een quantumlogica van proposities over metingen en meetuitkomsten te construeren op basis van empirische niet-probabilistische voorspellingen van de quantummechanica. In de herformulering zijn quantumkansfuncties conditionele kansfuncties op deze quantumlogica.The use of probability theory is widespread in our daily life (gambling, investments, etc.) as well as in scientific theories (genetics, statistical thermodynamics). In virtually all cases, calculations can be carried out within the framework of classical probability theory. A special exception is given by quantum mechanics (the physical theory that describes matter on the atomic scale), which gives rise to a new probability theory: quantum probability theory. This dissertation deals with the question of how this formalism can be understood from a philosophical and physical perspective.The dissertation is divided into three parts. In the first part, the formalism of quantum probability theory and its relation to quantum mechanics is presented. The second part considers the possibility of reformulating quantum probability theory to embed it within classical probability. Mathematically, this possibility overlaps with the possibility of the existence of hidden variables theories of quantum mechanics: theories that attempt to solve fundamental problems in quantum mechanics by introducing additional physical properties of systems. The conclusion of this part is that, although classical reformulations of quantum probability theory are formally possible, they offer little insight into the formalism of quantum probability theory itself. The third part regards a more direct investigation of quantum probability theory. A reformulation of quantum probability theory is obtained by constructing a quantum logic on the basis of empirical non-probabilistic predictions of quantum mechanics. In this reformulation quantum probability functions are conditional probability functions on an algebra of propositions about measurements and measurement outcomes
Strategies to Improve Outcome after Transplantation of Extended Criteria Donor Livers
No full textTo reduce the current imbalance between available donor livers and patients waiting for a new liver graft, suboptimal donor livers are increasingly accepted for liver transplantation. Examples of suboptimal donor livers are livers derived from elderly donors or donors with a fatty liver due to overweight. Unfortunately, these suboptimal donor livers are more prone for the period of ischemia, which occurs when the donor liver is transported between the donation and transplantation hospital. Because of this higher vulnerability for ischemia, suboptimal donor livers are related to a higher degree of tissue injury and subsequently poorer postoperative outcomes.The subject of Andrie Westerkamp’s PhD thesis was to examine different strategies to improve the outcome after transplantation of suboptimal donor livers. First, the PhD candidate concluded that a short cold ischemia time is necessary when elderly and fatty donor livers are accepted for transplantation.Nowadays, no methods are available that can examine the degree of fat quickly and accurately in the short time frame of a donation procedure. Westerkamp and co-workers demonstrated that spectrometry is able to measure the degree of liver fat very accurately and in-real time. Finally, Westerkamp showed that machine perfusion, a new potential preservation technique, improves the quality of suboptimal donor livers compared to the current preservation method, static cold storage. Moreover, the PhD candidate concluded that independent of the perfusion temperature, machine perfusion is also able to reduce the degree of ischemic injury to the bile ducts
Three Month Follow-Up of Rat Mild Traumatic Brain Injury:A Combined [18F]FDG and [11C]PK11195 Positron Emission Study
No full textMild traumatic brain injury (mTBI) is the most common cause of head trauma. The time course of functional pathology is not well defined, however. The purpose of this study was to evaluate the consequences of mTBI in rats over a period of 3 months by determining the presence of neuroinflammation ([11C]PK11195) and changes in brain metabolism ([18F]FDG) with positron emission tomography (PET) imaging. Male Sprague-Dawley rats were divided in mTBI (n = 8) and sham (n = 8) groups. In vivo PET imaging and behavioral tests (open field, object recognition, and Y-maze) were performed at different time points after induction of the trauma. Differences between groups in PET images were explored using volume-of-interest and voxel-based analysis. mTBI did not result in death, skull fracture, or suppression of reflexes. Weight gain was reduced (p = 0.003) in the mTBI group compared with the sham-treated group. No statistical differences were found in the behavioral tests at any time point. Volume-of-interest analysis showed neuroinflammation limited to the subacute phase (day 12) involving amygdala, globus pallidus, hypothalamus, pons, septum, striatum, and thalamus (p < 0.03, d > 1.2). Alterations in glucose metabolism were detected over the 3 month period, with increased uptake in the medulla (p < 0.04, d ≥ 1.2), and decreased uptake in the globus pallidus, striatum, and thalamus (p < 0.04, d ≤ 1.2). Similar findings were observed in the voxel-based analysis (p < 0.05 at corrected cluster level). As a consequence of the mTBI, and in the absence of apparent behavioral alterations, relative brain glucose metabolism was found altered in several brain regions, which mostly correspond with those presenting neuroinflammation in the subacute stage.</p
Pharmacokinetics of ertapenem in patients with multidrug-resistant tuberculosis
No full textTreatment of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) is becoming more challenging because of increased levels of drug resistance against second-line TB drugs. One promising group of antimicrobial drugs is carbapenems. Ertapenem is an attractive carbapenem for the treatment of MDR- and XDR-TB because its relatively long half-life enables once-daily dosing.A retrospective study was performed for all patients with suspected MDR-TB at the Tuberculosis Center Beatrixoord of the University Medical Center Groningen (Haren, the Netherlands) who received ertapenem as part of their treatment regimen between December 1, 2010 and March 1, 2013. Safety and pharmacokinetics were evaluated.18 patients were treated with 1000 mg ertapenem for a mean (range) of 77 (5-210) days. Sputum smear and culture were converted in all patients. Drug exposure was evaluated in 12 patients. The mean (range) area under the concentration-time curve up to 24 h was 544.9 (309-1130) h.mg.L-1. The mean (range) maximum observed plasma concentration was 127.5 (73.9-277.9) mg.L-1.In general, ertapenem treatment was well tolerated during MDR-TB treatment and showed a favourable pharmacokinetic/pharmacodynamic profile in MDR-TB patients. We conclude that ertapenem is a highly promising drug for the treatment of MDR-TB that warrants further investigation.</p
Dynamic postural stability differences between male and female players with and without ankle sprain
No full textObjectives: To evaluate dynamic stability index (DSI) differences between males and females for different jump directions. To examine both preseason DSI differences between players with and without a history of ankle sprain, and between players with and without an ankle sprain during the subsequent season.Design: Prospective cohort design.Setting: Laboratory.Participants: 47 male (22.9 +/- 3.9 y) and 19 female (21.5 +/- 2.9 y) sub-elite and elite team sport players. Main outcome measures: Ankle sprain history was collected using an injury history questionnaire. DSI of a single-leg hop-stabilization task measured preseason was collected using force plates and calculated using a Matlab program. Ankle sprains were reported during the subsequent season.Results: Male players demonstrated larger DSI than female players on forward medial/lateral stability index (MLSI) and vertical stability index (VSI), diagonal VSI, and lateral anterior/posterior stability index (APSI) and VSI. Forward, diagonal and lateral dynamic postural stability indices (DPSI) were larger for males (p <0.001). No significant differences were found between players with and without a previous ankle sprain nor between players with and without an ankle sprain during the subsequent season.Conclusion: Male players showed larger DSI scores than female players, indicating lower dynamic stability. Sex-specific training sessions or prevention programs should be developed. (C) 2015 Elsevier Ltd. All rights reserved.</p
Bacterial dynamin as a membrane puncture repair kit
No full textDynamin(-like) proteins (DLPs) are widely distributed inbacteria, and both structural and biochemical data haveclearly demonstrated that, like their eukaryotic counter-parts, these proteins can function in membrane modelling.Although various functions for bacterial DLPs have beenhypothesized, a clear function for these proteins withinbacteria remained an enigma. A new study by Bramkampand colleagues (Sawantet al., 2016) provides the firstglimpse for a role of bacterial dynamins as a surveillancesystem that monitors membrane integrity and that coun-teracts pore formation by phages and antibiotics
Development and initial validation of prescribing quality indicators for patients with chronic kidney disease
No full textBACKGROUND: Quality assessment is a key element for improving the quality of care. Currently, a comprehensive indicator set for measuring the quality of medication treatment in patients with chronic kidney disease (CKD) is lacking. Our aim was to develop and validate a set of prescribing quality indicators (PQIs) for CKD care, and to test the feasibility of applying this set in practice.METHODS: Potential indicators were based on clinical practice guidelines and evaluated using the RAND/UCLA Appropriateness Method. This is a structured process in which an expert panel assesses the validity of the indicators. Feasibility was tested in a Dutch primary care database including >4500 diabetes patients with CKD.RESULTS: An initial list of 22 PQIs was assessed by 12 experts. After changing 10 PQIs, adding 2 and rejecting 8, a final list of 16 indicators was accepted by the expert panel as valid. These PQIs focused on the treatment of hypertension, albuminuria, mineral and bone disorder, statin prescribing and possible unsafe medication. The indicators were successfully applied to measure treatment quality in the primary care database, but for some indicators the number of eligible patients was too small for reliable calculation. Results showed that there was room for improvement in the treatment quality of this population.CONCLUSIONS: We developed a set of 16 PQIs for measuring the quality of treatment in CKD patients, which had sufficient content and face validity as well as operational feasibility. These PQIs can be used to point out priority areas for improvement.</p