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1.
Analysis of count data from clinical trials using mixed effect analysis has recently become widely used. However, algorithms
available for the parameter estimation, including LAPLACE and Gaussian quadrature (GQ), are associated with certain limitations,
including bias in parameter estimates and the long analysis runtime. The stochastic approximation expectation maximization
(SAEM) algorithm has proven to be a very efficient and powerful tool in the analysis of continuous data. The aim of this study
was to implement and investigate the performance of a new SAEM algorithm for application to count data. A new SAEM algorithm
was implemented in MATLAB for estimation of both, parameters and the Fisher information matrix. Stochastic Monte Carlo simulations
followed by re-estimation were performed according to scenarios used in previous studies (part I) to investigate properties
of alternative algorithms (Plan et al., 2008, Abstr 1372 []). A single scenario was used to explore six probability distribution models. For parameter estimation, the relative bias
was less than 0.92% and 4.13% for fixed and random effects, for all models studied including ones accounting for over- or
under-dispersion. Empirical and estimated relative standard errors were similar, with distance between them being <1.7% for
all explored scenarios. The longest CPU time was 95 s for parameter estimation and 56 s for SE estimation. The SAEM algorithm
was extended for analysis of count data. It provides accurate estimates of both, parameters and standard errors. The estimation
is significantly faster compared to LAPLACE and GQ. The algorithm is implemented in Monolix 3.1, (beta-version available in
July 2009). 相似文献
2.
Ibolja Cernak Jovan Savic Gordana Zunic Nada Pejnovic Olivera Jovanikic Vladislav Stepic 《World journal of surgery》1999,23(1):44-53
n
= 665, 51%)
had an ISS ranging from 0 to 34 (mean 13) had wounds ranging from G1ST
(soft tissue wounds caused by low energy transfer) to G3VF (massive
wounds with fractures and injury of vital structures) according to the
RCWC, with PSS/IS scores from 2 to 105 (mean 60). Statistically
significant correlation was found between ISS and PSS/IS as well as
RCWC and PSS/IS. Cytokines (IL-1, TNF
alpha
) and amino acids
responded to a blast injury in similar manner as to gunshot wounds with
a greater ISS or more severe RCWC injury type. The subjective
sensations in blasted patients (deafness, thoracic pain, vertigo) and
mediators, confirmed in previous experimental investigations as
important factors in the pathogenesis of blast injuries
(TxA
2
, sulfidopeptide leukotrienes) were relationed only to
the PSS/IS.RID=" ID=" <E5>Correspondence to:</E5> I. Cernak, M.D., Ph.D. 相似文献
3.
4.
Ferretti JJ McShan WM Ajdic D Savic DJ Savic G Lyon K Primeaux C Sezate S Suvorov AN Kenton S Lai HS Lin SP Qian Y Jia HG Najar FZ Ren Q Zhu H Song L White J Yuan X Clifton SW Roe BA McLaughlin R 《Proceedings of the National Academy of Sciences of the United States of America》2001,98(8):4658-4663
The 1,852,442-bp sequence of an M1 strain of Streptococcus pyogenes, a Gram-positive pathogen, has been determined and contains 1,752 predicted protein-encoding genes. Approximately one-third of these genes have no identifiable function, with the remainder falling into previously characterized categories of known microbial function. Consistent with the observation that S. pyogenes is responsible for a wider variety of human disease than any other bacterial species, more than 40 putative virulence-associated genes have been identified. Additional genes have been identified that encode proteins likely associated with microbial "molecular mimicry" of host characteristics and involved in rheumatic fever or acute glomerulonephritis. The complete or partial sequence of four different bacteriophage genomes is also present, with each containing genes for one or more previously undiscovered superantigen-like proteins. These prophage-associated genes encode at least six potential virulence factors, emphasizing the importance of bacteriophages in horizontal gene transfer and a possible mechanism for generating new strains with increased pathogenic potential. 相似文献
5.
Igor Mrdovic Mirko Čolić Lidija Savic Gordana Krljanac Peter Kruzliak Ratko Lasica Milika Asanin Sanja Stanković Jelena Marinkovic 《Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy》2016,30(2):151-158
Aims
The objective of the present substudy was to examine whether aspirin poor/high responsiveness (APR/AHR) is associated with increased rates of major adverse cardiovascular events (MACE) and serious bleeding after primary percutaneous coronary intervention (PPCI).Methods
We analyzed 961 consecutive ST-elevation acute myocardial infarction patients who underwent PPCI between February 2008 and June 2011. Multiplate analyser (Dynabite, Munich, Germany) was used for the assessment of platelet reactivity. APR/AHR were defined as the upper/lower quintiles of ASPI values, determined 24 h after aspirin loading. APR patients were tailored using 300 mg maintenance dose for 30 days. The co-primary end points at 30 days were: MACE (death, non-fatal infarction, ischemia-driven target vessel revascularization and ischemic stroke) and serious bleeding according to the BARC classification.Results
One hundred and 90 patients were classified as APR, and 193 patients as AHR. At admission, compared with aspirin sensitive patients (ASP), patients with APR had more frequently diabetes, anterior infarction and heart failure, while AHR patients had reduced values of creatine kinase, leukocytes, heart rate and systolic blood pressure. Compared with ASP, the rates of 30-day primary end points did not differ neither in APR group including tailored patients (MACE, adjusted OR 1.02, 95%CI 0.47-2.17; serious bleeding, adjusted OR 1.92, 95%CI 0.79-4.63), nor in patients with AHR (MACE, adjusted OR 1.58, 95%CI 0.71-5.51; serious bleeding, adjusted OR 0.69, 95%CI 0.22-2.12).Conclusions
The majority of APR patients were suitable for tailoring. Neither APR including tailored patients nor AHR were associated with adverse 30-day efficacy or safety clinical outcomes.6.
7.
Progression of kidney damage was studied in 18 patients with Balkan endemic nephropathy (BEN), with a mean 15-year follow-up after renal biopsy. According to kidney function, estimated by 99mTc-DTPA clearance, patients were divided into three groups: with apparently normal kidney function (clearance 103.5 ± 21.3 mL/min/1.73 m2), with incipient renal failure (clearance 65.5 ± 11.3), and with advanced renal failure (clearance 28.0 ± 6.2). The mean yearly decrease of glomerular filtration rate was 2.74 mL/min. In two patients, an increase of kidney function was recorded. Six patients become dialysis dependent, two from the group with incipient renal failure, but all four from the group with advanced renal failure. Three patients died after 8 to 12 years of follow-up, one from causes unrelated to kidney disease and two from end-stage renal failure. This study has shown that BEN is characterized by a slow course and prolonged evolution, modified by medical supervision and treatment. 相似文献
8.
N. Suhm C. Meier M. Kraenzlin E. Kungler B. Savic S. Mueller M. Jakob D. Rikli 《Der Unfallchirurg》2016,119(1):12-17
The increasing importance of preventive measures in the field of orthopedics and trauma surgery becomes apparent because of the demographic changes and the high risk for secondary fractures following osteoporotic fractures. Within the fracture treatment chain, orthopedics and trauma surgery are in the “pole position” to initiate these measures in geriatric patients. In the past orthopedists and trauma surgeons have constantly accused of neglecting secondary fracture prevention in fragility fracture patients. There are several reasons that speak in favor of us undertaking a role in secondary fracture prevention: osteoporosis medication is highly effective in fracture prevention when correctly indicated, the positive effects of osteoporosis therapy on fracture healing and legal issues. Arguments that have been used to justify neglect of secondary fracture prevention are undesired side effects related to osteoporosis medications, such as atypical femoral fractures and osteonecrosis of the jaws, interference of some specific drugs with fracture healing and the working conditions in emergency departments. These run contrary to the consideration of chronic diseases such as osteoporosis, secondary osteoporosis and the underlying disease could be overlooked and the increasing complexity of medicinal osteoporosis therapy. 相似文献
9.
10.
Svetlana Kostić Ivan Tasić Dragan Mijalković Dragan Lović Dragan Djordjević Todorka Savić Nataša Miladinović Tasić Aleksandra Aranđelović 《Central European Journal of Medicine》2014,9(5):601-608