Characterization of anti-drug antibody dynamics using a bivariate mixed hidden-markov model by nonlinear-mixed effects approach.

Biological therapies may act as immunogenic triggers leading to the formation of anti-drug antibodies (ADAs). Population pharmacokinetic (PK) models can be used to characterize the relationship between ADA and drug disposition but often rely on the ADA bioassay results, which may not be sufficiently sensitive to inform on this characterization.In this work, a methodology that could help to further elucidate the underlying ADA production and impact on the drug disposition was explored.

Population pharmacokinetics and pharmacodynamics of efmarodocokin alfa (IL-22Fc).

Efmarodocokin alfa (IL-22Fc) is a fusion protein of human IL-22 linked to the crystallizable fragment (Fc) of human IgG4. It has been tested in multiple indications including inflammatory bowel disease (IBD). The purposes of the present analyses were to describe the population pharmacokinetics (PK) of efmarodocokin alfa and perform pharmacodynamic (PD) analysis on the longitudinal changes of the PD biomarker REG3A after efmarodocokin alfa treatment as well as identify covariates that affect efmarodocokin alfa PK and REG3A PD.

Handling underlying discrete variables with bivariate mixed hidden Markov models in NONMEM.

Non-linear mixed effects models typically deal with stochasticity in observed processes but models accounting for only observed processes may not be the most appropriate for all data. Hidden Markov models (HMMs) characterize the relationship between observed and hidden variables where the hidden variables can represent an underlying and unmeasurable disease status for example. Adding stochasticity to HMMs results in mixed HMMs (MHMMs) which potentially allow for the characterization of variability in unobservable processes.

Sensitivity of Pegfilgrastim Pharmacokinetic and Pharmacodynamic Parameters to Product Differences in Similarity Studies.

In this work, a previously developed pegfilgrastim (PG) population pharmacokinetic-pharmacodynamic (PKPD) model was used to evaluate potential factors of importance in the assessment of PG PK and PD similarity. Absolute neutrophil count (ANC) was the modelled PD variable. A two-way cross-over study was simulated where a reference PG and a potentially biosimilar test product were administered to healthy volunteers.

Model-based evaluation of low-dose factor VIII prophylaxis in haemophilia A.

Introduction: The optimal treatment modality for haemophilia A is lifelong prophylaxis which is expensive and may not be implementable everywhere where factor VIII (FVIII) availability is limited. A less costly alternative to prophylaxis is low-dose prophylaxis (LDP) which was compared to conventional prophylaxis in this model-based simulation study.

Aim: To explore whether LDP is motivated where standard prophylaxis is not implementable, including evaluating LDP efficacy compared to high-dose prophylaxis and investigating the potential economic benefit of individualized dosing.

A Population Pharmacokinetic-Pharmacodynamic Model of Pegfilgrastim.

Neutropenia and febrile neutropenia (FN) are serious side effects of cytotoxic chemotherapy which may be alleviated with the administration of recombinant granulocyte colony-stimulating factor (GCSF) derivatives, such as pegfilgrastim (PG) which increases absolute neutrophil count (ANC). In this work, a population pharmacokinetic-pharmacodynamic (PKPD) model was developed based on data obtained from healthy volunteers receiving multiple administrations of PG. The developed model was a bidirectional PKPD model, where PG stimulated the proliferation, maturation, and margination of neutrophils and where circulating neutrophils in turn increased the elimination of PG.

Reduced and optimized trial designs for drugs described by a target mediated drug disposition model.

Monoclonal antibodies against soluble targets are often rich and include the sampling of multiple analytes over a lengthy period of time. Predictive models built on data obtained in such studies can be useful in all drug development phases. If adequate model predictions can be maintained with a reduced design (e.

Population pharmacokinetics of plasma-derived factor IX: procedures for dose individualization.

Background: Population pharmacokinetic (POPPK) models describing factor IX (FIX) activity levels in plasma, in combination with individual FIX measurements, may be used to individualize dosing in the treatment of hemophilia B.

Objectives: The aim was to reevaluate a previously developed POPPK model for FIX activity and to explore the number and timing of FIX samples required in pharmacokinetic (PK) dose individualization.

Methods: The POPPK model was reevaluated using an extended data set.

Smoking, rheumatoid factor isotypes and severity of rheumatoid arthritis.

Objectives: Smokers have an increased incidence of rheumatoid factor (RF) and rheumatoid arthritis (RA) and one report has also indicated that smoking may also adversely influence the severity of RA.

Methods: Sixty-three women with advanced RA answered a structured questionnaire that included detailed information about their smoking history. The women were also evaluated clinically and radiologically.

[Telemedicine. Information technology and health-care planning.].

The purpose of this article is to demonstrate how the development of telemedicine has been in close context with the rapid development of information technology. The increased use of telemedicine has resulted in strategic planning by health authorities of how to increase access to specialist consultation. Overview is given of existing and coming telemedicine projects in Iceland.

[Telemedicine in iceland.].

The aim of this survey is to consider the evolution and historical background of telemedicine, as well as reviewing the present status, globally, and locally. General definitions and aims of telemedicine are mentioned and discussed, examples of successful telemedicine implementations in various areas are presented, especially mentioning Canada, Australia and Norway. In Iceland only a few projects within telemedicine have been tried so far; the most extensive one being the successful establishment of a few teleradiology links.

Hypermobility associated with osteoarthritis of the thumb base: a clinical and radiological subset of hand osteoarthritis.

Objectives: To study the impact of articular hypermobility on the clinical and radiological features of hand osteoarthritis (OA) and to investigate whether hand osteoarthritis associated with hypermobility should be considered a separate subset of hand OA.

Methods: Fifty consecutive female patients with clinical hand OA and thumb base symptoms were examined for hypermobility according to the Beighton criteria.

Results: Thirty one of the 50 patients had hypermobility features (Beighton score > or = 2) and 17 patients fulfilled four or more Beighton criteria.

[X-ray- and other medical imaging in Iceland 1993. Assessed and compared with earlier surveys.].

A country-wide survey of the use and utilization of medical imaging in Iceland was undertaken, by gathering of available information for the year 1993. The aim was primarily to assess the overall consumption of these services, with regard to radiation and the impact of other imaging modalities. Reference was made to earlier studies of the same kind adding a more specified break-down of information regarding age and sex as well as types of examination.

[The commencement of radiology in Iceland: the pioneer.].

This essay deals with the pioneering work of Dr. Gunnlaugur Claessen (1881-1948), who introduced radiology into Iceland under very adverse conditions in 1914. His lifelong work and progress as a leader and teacher within that field is described.

Use of X-rays in family practice. A multicentre study.

Practicing physicians, faced with pressure to control health care costs, are increasingly being asked to incorporate considerations of cost into their decisions regarding the care they offer their patients. Accordingly, it is of importance to know how the money is spent. The use and cost of X-rays in family practice, and what factors influence it, is not well known.

Angiographic predictors of new coronary occlusions.

To determine whether coronary angiography is predictive of the future site of coronary occlusion, we analyzed the coronary angiograms of 246 consecutive patients having two or more angiograms without therapeutic invasive intervention in the interval between angiograms. The average interval between studies was 46 months. Of 2183 normal segments at the first angiogram, 51 (2.

Intraarticular ganglion between the cruciate ligaments of the knee. A case report.

Intraarticular ganglion cysts arising from the cruciate ligaments are rare. Only 9 cases have been described in the literature. Only in one case was the diagnosis suggested before operation by the appearance on MR imaging.

Methotrexate treatment of rheumatoid arthritis: effects on radiological progression.

Radiological progression was evaluated in 15 patients with rheumatoid arthritis (RA) treated with methotrexate (MTX). Prior to MTX treatment, all the patients had failed on other slow-acting agents and all showed radiological deterioration. For each patient, three sets of radiographs of hands and wrists were evaluated: prior to MTX treatment while on other slow-acting agents, at the beginning of MTX treatment, and at the most recent evaluation on MTX.

Relation between bone erosions and rheumatoid factor isotypes.

Total rheumatoid factor (RF) activity and individual RF isotypes were measured in 62 patients with rheumatic diseases. Retrospective analysis of available x rays showed an association between IgA RF and the occurrence of periarticular bone erosions in hands. In contrast, IgG RF and IgM RF did not show any significant association with erosions.

Mass screening for breast cancer.

Breast cancer is now the most common cancer in women. There is a certain correlation between the stage of the disease at diagnosis and outcome after treatment. Several studies have been initiated involving mammography with or without physical examination aimed at early detection of breast cancer in asymptomatic women.

The penetration of metrizamide into the brain after routine lumbar myelography as shown by cerebral computed tomography and its effect on auditory brainstem transmission time.

Metrizamide is a widely used contrast medium with some well known adverse reactions. In a preliminary study, CT scans and brain stem evoked potentials (BAEP) were done before and 18 hours following lumbar myelography on 12 patients. A statistically significant prolongation of the BAEP was observed.

Radiographic examination of the lumbosacral spine: an 'age-stratified' study.

Of a total of 99 922 radiological requests, 3.3% were for examinations of the lumbosacral spine. An 'age-stratified' study of 657 females aged 15-44 years referred for lumbosacral examination was carried out.

Diagnostic sensitivity of X-ray examination of the large bowel in colorectal cancer.

All individuals subjected to x-ray examination of the large bowel at Borgarspitalinn, Reykjavik, over the 5-year period 1975-1979 were matched against the files of the Icelandic Cancer Registry, 1955-1980 inclusively. The diagnostic accuracy was 84.9% and with additional proctoscopy the diagnostic accuracy was 92.