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Biomedical subjects

Anand Kumar

Publications and source records attributed to Anand Kumar.

At least 55 records · Page 3Linked to original sources

Mapping brain size and cortical gray matter changes in elderly depression.

BACKGROUND: In elderly depression, volumetric brain imaging findings suggest abnormalities of the frontal lobe, particularly the orbitofrontal cortex, and the hippocampus. No studies to date have mapped cortical abnormalities over the entire brain surface in major depression. Here, we conducted detailed spatial analyses of brain size and gray matter within the cortical mantle in elderly patients with major depression. METHODS: High-resolution, three-dimensional, structural magnetic resonance imaging data and cortical pattern matching methods were used in 24 depressed elderly patients and 19 group-matched controls to measure local brain size and proportions of gray matter at thousands of homologous cortical surface locations. RESULTS: Prominent brain size reductions were observed in the depressed subjects in the orbitofrontal cortex bilaterally. Cortical gray matter measurements revealed significant gray matter increases in the orbitofrontal cortex, adjacent to focal trend level significant decreases of gray matter in the same region. Depressed patients also exhibited significant gray matter increases in parietal cortices, as well as the left temporal cortex. CONCLUSIONS: Complex cortical changes may contribute to the brain size reduction of the orbitofrontal cortex and to the gray matter abnormalities detected in orbitofrontal cortex and temporoparietal cortices, thereby providing a potentially new window into the pathophysiology of elderly depression.

Aged↗

Biophysical changes in normal-appearing white matter and subcortical nuclei in late-life major depression detected using magnetization transfer.

Neuroanatomical changes have been identified in patients diagnosed with late-life major depressive disorder (MDD) compared with controls. These primarily comprise a decrease in focal brain volumes and an increase in MRI-determined high intensity lesions that are largely confined to the white matter. The physiological status of normal-appearing white matter in patients with MDD remains unknown. Magnetization transfer (MT) is a relatively new neuroimaging technique that permits us to examine the biophysical characteristics of specific brain regions. Using MT, we studied eight patients with late-life MDD and eight non-depressed controls. MT ratios (MTR), which reflect the integrity of the macromolecular protein pool, were ascertained in normal-appearing white matter and subcortical nuclei. Patients had significantly lower MTRs in the genu and splenium of the corpus callosum, the right caudate nucleus and putamen, and the occipital white matter compared with controls. The findings indicate that the structure of the macromolecular protein matrix may be compromised in normal-appearing white matter and critical subcortical nuclei in patients with late-life major depression. These changes may provide important substrates to mood disorders and have implications for neuronal connectivity and its role in the pathophysiology of late-life depression.

Aged↗

Neurochemistry of late-life major depression: a pilot two-dimensional MR spectroscopic study.

PURPOSE: To evaluate a two-dimensional localized chemical shift correlated spectroscopy (L-COSY) sequence in elderly patients with major depression. MATERIALS AND METHODS: A total of 33 healthy elderly subjects and 15 elderly patients with major depression were investigated. A voxel size of 3 x 3 x 3 cm3 was chosen in the dorsolateral prefrontal region with predominantly white matter, with the use of three slice-selective radiofrequency (RF) pulses (90 degrees , 180 degrees , and 90 degrees). A chemical shift-selective (CHESS) sequence was used prior to volume localization for the presaturation of water. The two-dimensional raw data matrix consisted of 1024 complex points along the detection period (t2), and 100 increments along the evolution period (t1), resulting in a total acquisition time of approximately 27 minutes per acquisition. The metabolite ratios were calculated using the two-dimensional peak volumes with respect to the diagonal peak volume of total creatine (Cr) at 3.0 ppm. RESULTS: In the 33 elderly subjects, the mean ratio of choline (Cho) to Cr was 10% higher in men compared to women (P < 0.05), consistent with earlier findings obtained by one-dimensional MRS. When the metabolite ratios were compared in a subsample of 16 elderly female controls and 12 depressed female patients, the depressed geriatric patients had higher levels of myoinositol (mI), phosphoethanolamine (PE), and glutamate/glutamine (Glx) than the controls, although the differences were not statistically significant. CONCLUSION: Our pilot study shows the feasibility of performing two-dimensional L-COSY successfully in elderly subjects and patients with late-life mood disorders. These findings are consistent with and expand on our earlier findings in major depressive disorder (MDD) detected with one-dimensional MRS.

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Prevalence of multiple micronutrient deficiencies amongst pregnant women in a rural area of Haryana.

UNLABELLED: Deficiencies of micronutrients (zinc, iron, folic acid and iodine) during pregnancy are known causes of Low Birth Weight (LBW). Studies have documented status of one or two micronutrients amongst pregnant women (PW). However, no attempt has been made to concurrently assess the prevalence of multiple micronutrient deficiencies and the factors associated with them amongst PW. OBJECTIVE: The present study was undertaken to assess the prevalence of multiple micronutrient deficiencies amongst PW in a rural area. METHODS: A community based cross sectional survey was conducted in six villages of a rural area of district Faridabad in Haryana state, India during November 2000 and October 2001. All PW aged 18 years or more, with pregnancy duration of more than 28 weeks were enrolled. Data were collected on socio-economic status and other demographic parameters. Serum zinc, copper and magnesium levels were estimated by utilizing the Atomic absorption spectrophotometry (AAS); serum ferritin and folate was estimated by Enzyme Linked Immuno Sorbent Assay (ELISA) method and the Radio-Immuno Assay (RIA) method, respectively and serum thyroid stimulating hormone (TSH) level was estimated by the Abbot AxSYM System. Serum zinc, copper, magnesium, ferritin, and folate levels less than 70.0 microg/dl, 80.0 microg/dl, 1.80 mg/dl, 15 ng/ml, and 3 ng/ml, respectively were considered as indicative of deficiency for respective micronutrients. The TSH levels of 4.670 and more indicated iodine deficiency status. Dietary intake of micronutrients was assessed utilizing 1-day 24-hour dietary recall methodology. Food consumption pattern was assessed utilizing the food frequency questionnaire methodology. RESULTS: Nearly 73.5, 2.7, 43.6, 73.4, 26.3, and 6.4 percent PW were deficient in zinc, copper, magnesium, iron, folic acid and iodine, respectively. The highest concurrent prevalence of two, three, four and five micronutrient deficiency was of zinc and iron (54.9%); zinc, magnesium and iron (25.6%); zinc, magnesium, iron and folic acid (9.3%) and zinc, magnesium, iron, folic acid and iodine (0.8%), respectively. No pregnant woman was found to have concomitant deficiencies of all the six micronutrients. Dietary intake data revealed an inadequate nutrient intake. Over 19% PW were consuming less than 50% of the recommended calories. Similarly, 99, 86.2, 75.4, 23.6, 3.9 percent of the PW were consuming less than 50% of the recommended folic acid, zinc, iron, copper, and magnesium. The consumption of food groups rich in micronutrients (pulses, vegetables, fruits, nuts and oil seeds, animal foods) was infrequent. Univariate and Multivariate logistic regression analysis revealed that low dietary intake of nutrients, low frequency of consumption of food groups rich in micronutrients and increased reproductive cycles with short interpregnancy intervals were important factors leading to micronutrient deficiencies. CONCLUSION: There was a high prevalence of micronutrient deficiencies amongst the PW of the area, possibly due to the poor dietary intake of food and low frequency of consumption of food groups rich in micronutrients. The concurrent prevalence of two, three, four and five micronutrient deficiencies were common.

Adolescent↗

The significance of subsyndromal depression in geriatrics.

Clinically significant non-major depression has been underinvestigated, despite its high prevalence and public health impact. Although there is increasing recognition of the importance of subsyndromal forms of depression, their nosologic boundaries and neurobiologic mechanisms remain largely unknown. This review discusses the literature pertaining to the current concepts, phenomenology, neurobiology, and treatment approaches for geriatric non-major clinically significant depression. The authors examine the similarities and differences between various subtypes of depressive disorders, and compare non-major clinically significant depression in the elderly with non-geriatric adult populations. The authors draw conclusions from the published literature and present clinical criteria for the diagnosis of clinically significant non-major depression in the elderly.

Age Factors↗

Executive dysfunction and visuospatial ability among depressed elders in a community setting.

Visuospatial ability is frequently compromised among elderly depressed patients, but it is unclear whether the impairment is a consequence of a visuospatial memory deficit or of an executive dysfunction that impacts visuospatial ability. The Boston Qualitative Scoring System is a method of scoring the Rey-Osterrieth Complex Figure (ROCF) that assesses the process used to draw the figure, the executive aspect of the task, as well as the accuracy and location of the completed elements. The hypotheses that executive scores as measured by the BQSS would separate diagnostic groups and that executive function would mediate the relationship between depression and nonverbal recall were tested using a between groups design with elderly depressed volunteers (N = 31) and healthy controls (N = 31). Participants were screened for other Axis I disorders with the Structured Clinical Interview for DSM-IV Diagnosis, diagnosed for major depression per DSM-IV criteria, and administered the ROCF. The copy and recall drawings were scored using BQSS criteria, and scores were grouped into executive and drawing scores from both copy and recall phases. Executive scores during the copy phase and drawing scores from the recall phase separated the diagnostic groups [F(1,59), = 4.14, P = .05] and [F(1,59) = 6.88, P = .01], respectively. Follow-up ANCOVAS showed that copy Planning, the score that quantified the process by which the figure was drawn, separated the diagnostic groups. Planning also mediated the association between depression and the percent of the figure recalled after the short delay (Z = 1.84, P < .05). The significance of the depression-to-recall pathway was eliminated when Planning was controlled for, but Planning remained related to percent recalled [B = -6.90, P < .007]. A dimension of executive dysfunction, represented here by Planning, may be one underlying source of the observed decline in nonverbal recall among elderly depressed patients. This result is consistent with the theory that dysfunction of the prefrontal cortex is a critical feature of late-life depression.

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Neurocognitive profiles in elderly patients with frontotemporal degeneration or major depressive disorder.

Major depressive disorder (MDD) and frontotemporal dementia (FTD) are both disorders in elderly populations that involve the prefrontal cortex and appear to have similar neurocognitive deficits. This review examined whether there are testable deficits in cognition that are consistent across individuals within the same neuropathological condition that could be used to facilitate early diagnoses. Medline and PsychInfo databases were searched for cognitive studies of depressed and FTD patients that used a matched control group and reported findings with means and standard deviations (N = 312). Effect sizes for FTD patients with mild and moderately advanced disease were compared to effect sizes within subgroups of depressed patients, such as inpatients, outpatients and community volunteers. Moderately advanced FTD patients were more impaired than depressed patients over all domains, particularly in language ability, although depressed inpatients appeared similar to FTD patients in some domains. Effect sizes for FTD patients who were in the mild, or early, stage of the disease (MMSE = 28) were similar to those of depressed outpatients but slightly worse than those of community volunteers in all domains except semantic memory and executive ability. In the latter two domains, even mild FTD patients had notably large deficits. All FTD patients showed more severe deficits in some domains relative to other domains. In contrast, depressed patients tended to vary by clinical presentation or disease severity, but the magnitude of impairment for each subgroup remained relatively consistent across domains and they did not have the severe focal deficits in one or two domains demonstrated by FTD patients.

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Brain metabolites and cognitive function among older depressed and healthy individuals using 2D MR spectroscopy.

Brain metabolites of choline (Ch) and myo-Inisotol (mI) have been reported as elevated among geriatric depressed patients. Two-dimensional (2D) magnetic resonance spectroscopy (MRS) provides estimates of Ch, mI, and creatine (Cr) similar to one-dimensional MRS, and it also estimates the resonances of the Ch-containing compounds of phosphoethanolamine (Pe) and phosphocholine (PCh). In this cross-sectional geriatric study, 14 depressed patients and 14 healthy volunteers who were comparable in age, gender, education, comorbid medical burden, and Mini-Mental State Examination (MMSE) scores completed 2D MRS and a neurocognitive battery. A voxel in the left dorsolateral cortex, which was comprised of approximately 60% white matter, was used to estimate the CR ratios of Ch, PCh, Pe, and mI. Composite scores for cognitive function were developed for verbal learning, recall, recognition, executive function, hypothesis generation, and processing speed. Among nondepressed subjects, cognition was positively correlated with Ch/Cr and mI/Cr and negatively correlated with PCh/Cr in four domains of verbal learning, recognition, recall, and hypothesis generation. In contrast, depressed patients did not have consistent relationships between Ch/Cr, mI/Cr, and PCh/Cr and cognition. There was a significant difference in the overall pattern of associations between the four metabolites and verbal learning and processing speed in depressed patients compared to healthy controls. The attenuated relationship between metabolites and specific cognitive domains in patients with late-life MDD suggests that the level of cognitive performance observed during depressive episodes may be associated with changes in biochemistry within the frontostriatal neuronal circuitry.

Age Factors↗

Validity of the Boston qualitative scoring system for the Rey-Osterrieth complex figure among depressed elderly patients.

A recent qualitative scoring method for the Rey-Osterrieth Complex Figure (ROCF), the Boston Qualitative Scoring System (BQSS), purports to assess visuospatial organization, visual memory and executive function by using multiple series of scores with well-defined criteria. The first objective of this study was to determine whether the BQSS cores correlated with scores derived from the tradition Osterrieth scoring method and which method was more efficient at separating the diagnostics groups. The second objective was to correlate the BQSS executive scores to other nonverbal and verbal tests of executive function, working memory, processing speed, and episodic memory to determine what cognitive abilities the BQSS scores were measuring. The subjects, older depressed patients and healthy controls, were free of any clinical sign of incipient dementia or comorbid neurological disease. Their ROCF drawings were scored using both the Osterrieth and BQSS methods. The BQSS summary drawing scores correlated well with the Osterrieth summary scores for the copy and short-delay recall phases, the percent retained over the delay period and recognition. The BQSS executive scores for Planning, which included both copy and recall phases, correlated with Matrix Reasoning indicating that they assessed nonverbal reasoning but they did not correlate with other traditional executive tests. Planning also contributed to the separation of diagnostics groups and was the most effective score for predicting the percent of the ROCF retained over a short delay. The remaining executive scores did not show a pattern of correlations with other nonverbal executive or working memory scores that would satisfy concerns regarding their interpretation or internal validity when used in an older and/or depressed population. No differences emerged between the two scoring methods in their efficiency for predicting depression.

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Bacterial DNA and RNA induce rat cardiac myocyte contraction depression in vitro.

Sepsis and septic shock, the systemic immunologic and pathophysiologic response to overwhelming infection, are associated with perturbation of a variety of metabolic cell pathways and with multiple organ failure (MOF) including cardiac depression. This depression has been attributed to the effect of several circulating and locally produced proinflammatory mediators. Recent data suggest that bacterial nucleic acids can produce profound systemic inflammatory responses characterized by circulatory shock in intact animals. In this study, bacterial DNA and RNA derived from pathogenic clinical S. aureus and E. coli isolates are shown to induce early concentration-dependent depression of maximum extent and peak velocity of contraction of electrically paced neonatal rat ventricular myocytes in culture. Significant but more modest depression was generated by a nonpathogenic E. coli isolate. Pretreatment with a DNase or RNase abrogated this effect. Further, synthetic, double-stranded RNA (dsRNA) also induced concentration-dependent depression of myocyte contraction, with the effect also being prevented by pretreatment with RNase. These data suggest that bacterial DNA and RNA may contribute to myocardial depression during bacterial sepsis and septic shock.

Animals↗

Pulmonary artery occlusion pressure and central venous pressure fail to predict ventricular filling volume, cardiac performance, or the response to volume infusion in normal subjects.

OBJECTIVE: Pulmonary artery occlusion pressure and central venous pressure have been considered to be reliable measures of left and right ventricular preload in patients requiring invasive hemodynamic monitoring. Studies in recent years have questioned the correlation between these estimates of ventricular filling pressures and ventricular end-diastolic volumes/cardiac performance variables in specific patient groups, but clinicians have continued to consider the relationship valid in the broader context. The objective of this study was to assess the relationship between pressure estimates of ventricular preload (pulmonary artery occlusion pressure, central venous pressure) and end-diastolic ventricular volumes/cardiac performance in healthy volunteers. DESIGN: Prospective, nonrandomized, nonblinded interventional study. SETTING: Cardiac catheterization and echocardiography laboratories. SUBJECTS: Normal healthy volunteers (n = 12 group 1, n = 32 group 2). INTERVENTIONS: Pulmonary catheterization and radionuclide cineangiography (group 1) and volumetric echocardiography (group 2) during 3 L of normal saline infusion over 3 hrs. MEASUREMENTS AND MAIN RESULTS: In group 1, the initial pulmonary artery occlusion pressure and central venous pressure did not correlate significantly with initial end-diastolic ventricular volume indexes or cardiac performance (cardiac index and stroke volume index). Changes in pulmonary artery occlusion pressure and central venous pressure following saline infusion also did not correlate with changes in end-diastolic ventricular volume indexes or cardiac performance. In contrast, initial end-diastolic ventricular volume indexes and changes in these ventricular volume indexes in response to 3 L of normal saline loading correlated well with initial stroke volume index and changes in stroke volume index, respectively. The relationship between left ventricular end-diastolic volume index and stroke volume index was confirmed in group 2 subjects using mathematically independent techniques to measure these variables. In addition, initial central venous pressure, right ventricular end-diastolic volume index, pulmonary artery occlusion pressure, and left ventricular end-diastolic volume index failed to correlate significantly with changes in cardiac performance in response to saline infusion in group 1 subjects. CONCLUSIONS: Normal healthy volunteers demonstrate a lack of correlation between initial central venous pressure/pulmonary artery occlusion pressure and both end-diastolic ventricular volume indexes and stroke volume index. Similar results are found with respect to changes in these variables following volume infusion. In contrast, initial end-diastolic ventricular volume indexes and changes in end-diastolic ventricular volume indexes in response to saline loading correlate strongly with initial and postsaline loading changes in cardiac performance as measured by stroke volume index. These data suggest that the lack of correlation of these variables in specific patient groups described in other studies represents a more universal phenomenon that includes normal subjects. Neither central venous pressure nor pulmonary artery occlusion pressure appears to be a useful predictor of ventricular preload with respect to optimizing cardiac performance.

Adolescent↗

Anterior cingulate, gyrus rectus, and orbitofrontal abnormalities in elderly depressed patients: an MRI-based parcellation of the prefrontal cortex.

OBJECTIVE: To examine structural abnormalities in subregions of the prefrontal cortex in elderly patients with depression, the authors explored differences in gray matter, white matter, and CSF volumes by applying a parcellation method based on magnetic resonance imaging (MRI). METHOD: Twenty-four elderly patients with major depression and 19 group-matched comparison subjects were studied with high-resolution MRI. Cortical surface extraction, tissue segmentation, and cortical parcellation methods were applied to obtain volume measures of gray matter, white matter, and CSF in seven prefrontal subregions: the anterior cingulate, gyrus rectus, orbitofrontal cortex, precentral gyrus, superior frontal cortex, middle frontal cortex, and inferior frontal cortex. RESULTS: Highly significant bilateral volume reductions in gray matter were observed in the anterior cingulate, the gyrus rectus, and the orbitofrontal cortex. Depressed patients also exhibited significant bilateral white matter volume reductions and significant CSF volume increases in the anterior cingulate and the gyrus rectus. Finally, the depressed group showed significant CSF volume reductions in the orbitofrontal cortex relative to the comparison subjects. None of the other regions examined revealed significant structural abnormalities. CONCLUSIONS: The prominent bilateral gray matter deficits in the anterior cingulate and the gyrus rectus as well as the orbitofrontal cortex may reflect disease-specific modifications of elderly depression. The differential pattern of abnormalities detected in the white matter and CSF compartments imply that distinct etiopathological mechanisms might underlie the structural cortical changes in these regions.

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Localizing gray matter deficits in late-onset depression using computational cortical pattern matching methods.

OBJECTIVE: The authors used magnetic resonance imaging and an image analysis technique known as cortical pattern matching to map cortical gray matter deficits in elderly depressed patients with an illness onset after age 60 (late-onset depression). METHOD: Seventeen patients with late-onset depression (11 women and six men; mean age=75.24, SD=8.52) and 17 group-matched comparison subjects (11 women and six men; mean age=73.88, SD=7.61) were included. Detailed spatial analyses of gray matter were conducted across the entire cortex by measuring local proportions of gray matter at thousands of homologous cortical surface locations in each subject, and these patterns were matched across subjects by using elastic transformations to align sulcal topography. To visualize regional changes, statistical differences were mapped at each cortical surface location in three dimensions. RESULTS: The late-onset depression group exhibited significant gray matter deficits in the right lateral temporal cortex and the right parietal cortex, where decreases were most pronounced in sensorimotor regions. The statistical maps also showed gray matter deficits in the same regions of the left hemisphere that approached significance after permutation testing. No significant group differences were detected in frontal cortices or any other anatomical region. CONCLUSIONS: Regionally specific decreases of gray matter occur in late-onset depression, supporting the hypothesis that this subset of elderly patients with major depression presents with certain unique neuroanatomical abnormalities that may differ from patients with an earlier onset of illness.

Age of Onset↗

Experimental human endotoxemia is associated with depression of load-independent contractility indices: prevention by the lipid a analogue E5531.

OBJECTIVE: To evaluate the efficacy of a novel lipopolysaccharide (LPS) antagonist, E5531, in blocking LPS-induced cardiac responses including myocardial depression (as assessed by relatively load-independent echocardiographic indices of contractility) in a human model of experimental endotoxemia. DESIGN: Randomized, prospective, placebo-controlled, double-blind trial. SETTING: ICU procedure room. PARTICIPANTS: Thirty-two healthy, male volunteers. INTERVENTIONS: Administration of LPS (4 ng/kg) and either a placebo or one of four sequential doses of E5531 (100 microg, 250 microg, 500 microg, or 1,000 microg) followed by volumetric echocardiography before and during 4-L saline solution infusion (3 L over 3 h, followed by 1 L over 2 h). RESULTS: In addition to the generation of a hyperdynamic circulation throughout the study period, administration of LPS resulted in a biphasic contractility response. Ejection fraction (EF), rate-corrected mean velocity of circumferential fiber shortening (Vcfc), peak systolic BP (SBP)/end-systolic volume index (ESVI) ratio, and end-systolic pressure (Pes)/ESVI ratio increased at the 3-h post-LPS assessment, compared to a control group of subjects receiving only similar amounts of saline solution (minimum p < 0.001). End-systolic myocardial wall stress (sigmaes)/ESVI ratio, one of the most load independent of the contractility indices, was unchanged. At 5 h after endotoxin, EF, Vcfc, SBP/ESVI, Pes/ESVI, and sigmaes/ESVI were all decreased (minimum p < 0.01), indicating myocardial depression. When present, early (3 h after LPS), apparent enhancement of myocardial contractility and later (5 h after LPS) myocardial depression were substantially blunted by administration of E5531 (minimum p < 0.025), typically in a concentration-dependent manner. CONCLUSIONS: Endotoxin generates significant myocardial depression when measured using highly load-independent indices of cardiac contractility. E5531 is a potent inhibitor of the early hyperdynamic cardiovascular and later myocardial depression response seen in experimental human endotoxemia.

Adolescent↗

Ontology-based error detection in SNOMED-CT.

Quality assurance in large terminologies is a difficult issue. We present two algorithms that can help terminology developers and users to identify potential areas of improvement. We demonstrate the methodology by applying the algorithms to one of the most popular terminologies, SNOMED-CT. Analysis of the results provides evidence for the thesis that both formal logical and linguistic tools should be used in the development and quality-assurance process of large terminologies.

Abstracting and Indexing↗

Context-based task ontologies for clinical guidelines.

Evidence-based medicine relies on the execution of clinical practice guidelines and protocols. A great deal of effort has been invested in the development of tools which can automate the representation and execution of the recommendations contained within such guidelines, by creating Computer Interpretable Guideline Models (CIGMs). Context-based task ontologies (CTOs), based on standard terminology systems like UMLS, form one of the core components of such models. We have created DAML+OIL-based CTOs for the tasks referred to in the WHO guideline for hypertension management, drawing comparisons also with other, related guidelines. The advantages of CTOs include: contextualization of ontologies, tailoring of ontologies to specific aspects of the phenomena of interest, division of the complex tasks involved in creating ontologies into different levels, and provision of a methodology by means of which the task recommendations contained within guidelines can be integrated into the clinical practices of a health care set-up.

Humans↗

An ontological framework for the implementation of clinical guidelines in health care organizations.

The paper presents the outlines of an ontology of plans and guidelines, which is then used as the basis for a framework for implementing guideline-based systems for the management of workflow in health care organizations. The framework has a number of special features, above all in that it enables us to represent in formal terms assignments of work-items both to individuals and to teams and to tailor guideline to specific contexts of application in health care organizations. It is designed also to enable implementations to do justice to the fact that the processes carried out in health care organizations may deviate in different ways from the norms set forth in corresponding guideline definitions. This means that implementations built in conformity with the framework will be marked by a type of flexibility that might make them more likely to be accepted by healthcare professionals than are standard guideline-based management systems.

Medical Informatics↗