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Formation of target-specific neuronal projections in organotypic slice cultures from rat visual cortex.

A characteristic feature of the mammalian cortex is that projection neurons located in distinct cortical layers send their axons to different targets. In visual cortex, cells in layers 2 and 3 project to other cortical areas, whereas cells in layers 5 and 6 project to subcortical targets such as the lateral geniculate nucleus. The proper development of these projections is crucial for correct functioning of the visual system. Here we show that specific connections are established in an organotypic culture system in which rat visual cortex slices are co-cultured with another slice of the visual cortex or with a thalamic slice. The laminar origin and cellular morphology in vitro of cortical projections to other cortical regions or to subcortical targets are remarkably similar to those seen in vivo. In addition, axons of projecting cells are not restricted to particular pathways, but appear instead to grow directly towards their appropriate target. These observations raise the possibility that chemotropic attraction from the target areas may play an important part in the development of the cortical projection pattern.

Afferent Pathways↗

Projection sites of medial preoptic area and ventral bed nucleus of the stria terminalis neurons that express Fos during maternal behavior in female rats.

Medial preoptic area (MPOA) and ventral bed nucleus of the stria terminalis (VBST) neurons are involved in maternal behavior, but the neural sites to which the maternally relevant neurons project have not been determined. Since MPOA and VBST neurons express Fos during maternal behavior, we used a double-labeling immunocytochemical procedure to detect both Fos and a retrograde tracer, wheat germ agglutinin (WGA), in order to determine where these Fos neurons project. On Day 4 postpartum, fully maternal females were separated from their litters. On Day 5, WGA was iontophoretically injected into one of the following regions known to receive MPOA and/or VBST input: Lateral septum, medial hypothalamus at the level of the ventromedial nucleus, lateral habenula, ventral tegmental area, retrorubral field, or periaqueductal gray. On Day 7, females received a 2-h test with either pups or candy, after which they were perfused and their brains were processed for the detection of Fos and WGA. As expected, females tested with pups had more Fos-containing neurons in the MPOA and VBST than did females tested with candy. After WGA injections into several brain sites, the number of double-labeled cells observed in the MPOA and VBST was greater for the maternal females when compared to the non-maternal females. Therefore, these results pinpointed neural circuits that were activated during maternal behavior. For the maternal females, Fos-containing neurons in the MPOA projected most strongly to the medial hypothalamus at the level of the ventromedial nucleus and to the lateral septum, while Fos-containing neurons in the VBST projected most strongly to the retrorubral field, ventral tegmental area, and medial hypothalamus. Although relatively few MPOA and VBST neurons which expressed Fos during maternal behavior projected to the periaqueductal gray, these Fos-expressing neurons made up a relatively large proportion of the MPOA and VBST projection to the periaqueductal gray. This study suggests that MPOA and VBST efferents project to a variety of regions to promote full maternal responsiveness.

Animals↗

Projections of nitric oxide synthase and vasoactive intestinal polypeptide-reactive submucosal neurons in the human colon.

BACKGROUND: The submucosal plexus is important in the control of secretomotor and motor function of the intestine. Our aim was to describe the projections of submucosal neurons to the mucosa within the submucosal plexus and to the circular muscle of human colon and to determine whether submucosal neurons that projected to different layers were located at different levels of the submucosa. METHODS: A retrogradely transported fluorescent dye was applied to the mucosa, submucosa or circular muscle layer of human colon which was then maintained in organotypic culture for 5 days. The submucosa was then dissected into two preparations, one containing the inner layer of the submucosal plexus and the other containing both the intermediate and outer layers. The dissected preparations were labelled with antibodies to nitric oxide synthase (NOS) or vasoactive intestinal peptide (VIP). RESULTS: Submucosal neurons projected to the mucosa, submucosa and circular muscle layers for mean distances of 3.7, 3.0 and 4.3 mm, respectively. Ninety-seven per cent of submucosal neurons labelled from the circular muscle were located in the outer or the intermediate layers, while 51% of those projecting to the mucosa were in inner layer and 49% in the intermediate/outer layers of the submucosal plexus. Eleven per cent of submucosal neurons projecting to the circular muscle were immunoreactive for NOS and 12% were immunoreactive for VIP. Forty-five per cent of those projecting within the submucosa were immunoreactive for VIP and 38% of those projecting to the mucosa were immunoreactive for VIP. CONCLUSIONS: Submucosal neurons in the human colon innervate the mucosa, circular muscle and submucosa and different functional classes of neurons are located in different layers of the submucosal plexus.

Adult↗

Neurokinin 1 receptor expression by neurons in laminae I, III and IV of the rat spinal dorsal horn that project to the brainstem.

Large neurons in laminae III and IV of the spinal cord which express the neurokinin 1 receptor and have dendrites that enter the superficial laminae are a major target for substance P (SP)-containing (nociceptive) primary afferents. Although some of these neurons project to the thalamus, we know little about other possible projection targets. The main aim of this study was to determine whether all cells of this type are projection neurons and to provide information about brainstem sites to which they project. Injections of cholera toxin B subunit were made into four brainstem areas that receive input from the spinal cord, and the proportion of cells of this type in the L4 spinal segment that were retrogradely labelled was determined in each case. The results suggest that most of these cells (>90%) project to the contralateral lateral reticular nucleus (or to a nearby region), while many (>60%) send axons to the lateral parabrachial area and some to the dorsal part of the caudal medulla. However, few of these cells project to the periaqueductal grey matter. As lamina I neurons with the neurokinin 1 receptor appear to be important in the generation of hyperalgesia, we also examined projection neurons in this lamina and found that for each injection site the great majority possessed the receptor. These results demonstrate that dorsal horn neurons which express the neurokinin 1 receptor contribute to several ascending pathways that are thought to be important in pain mechanisms.

Afferent Pathways↗

Evidence for glutamatergic projections from the cochlear nucleus to the superior olive and the ventral nucleus of the lateral lemniscus.

This study attempts to determine if projections ascending from the guinea pig cochlear nucleus (CN) could be glutamatergic and/or aspartatergic. Multiple radio frequency lesions were made to ablate the right CN. The ablation was verified histologically. To identify the principal targets of CN efferents, silver impregnation methods were used to localize the preterminal degeneration of fibers in transverse sections of the brainstem 5 and 7 days after CN ablation. CN efferents projected heavily to the lateral superior olive (LSO) ipsilaterally, the medial superior olive (MSO) bilaterally, and contralaterally to the medial (MNTB) and ventral (VNTB) nuclei of the trapezoid body, the ventral (VNLL) and intermediate nuclei of the lateral lemniscus and the central nucleus of the inferior colliculus (ICc). There were smaller projections to the lateral nucleus of the trapezoid body ipsilaterally, the dorsal and dorsomedial periolivary nuclei bilaterally, and the dorsal nucleus of the lateral lemniscus contralaterally. There were sparse projections to the VNLL and ICc ipsilaterally and the CN contralaterally, and a very sparse projection to the contralateral LSO. To determine if CN efferents were glutamatergic and/or aspartatergic, the fresh brainstem was sectioned transversely and samples of the LSO, MSO, MNTB, VNLL, and ICc were taken to measure the electrically evoked release and the uptake of D-[3H]Asp and [14C]Gly or [14C]GABA 3-5 days after the CN ablation. The release studies suggest that only certain of the histologically identified projections ascending from the CN may be glutamatergic and/or aspartatergic. CN ablation depressed D-[3H]Asp release in the MSO bilaterally and in the contralateral MNTB and VNLL, suggesting that the CN efferents to these nuclei may use glutamate or aspartate as a transmitter. It was unclear whether a marginal depression of D-[3H]Asp release in the ipsilateral LSO reflected the presence of glutamatergic CN projections to this nucleus. D-[3H]Asp release in the ICc was unaffected, suggesting that CN efferents to this nucleus may not be glutamatergic. There were no deficits in D-[3H]Asp uptake. [14C]Gly release from the LSO and MSO was unchanged. [14C]Gly uptake was unchanged in the MSO and depressed only in the contralateral LSO, possibly reflecting subnormal uptake activity in endings contributed by contralateral MNTB cells that had lost their CN efferents.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Specific neurochemical derangements of brain projecting neurons in apolipoprotein E-deficient mice.

Apolipoprotein E (apoE)-deficient mice provide a useful system for studying the role of apoE in neuronal maintenance and repair. Previous studies revealed specific memory impairments in these mice that are associated with presynaptic derangements in projecting forebrain cholinergic neurons. In the present study we examined whether dopaminergic, noradrenergic, and serotonergic projecting pathways of apoE-deficient mice are also affected and investigated the mechanisms that render them susceptible. The densities of nerve terminals of forebrain cholinergic projections were monitored histochemically by measurements of acetylcholinesterase activity, whereas those of the dopaminergic nigrostriatal pathway, the noradrenergic locus coeruleus cortical projection, and the raphe-cortical serotonergic tract were measured autoradiographically using radioligands that bind specifically to the respective presynaptic transporters of these neuronal tracts. The results obtained revealed that synaptic densities of cholinergic, noradrenergic, and serotonergic projections in specific brain regions of apoE-deficient mice are markedly lower than those of controls. Furthermore, the extent of presynaptic derangement within each of these tracts was found to be more pronounced the further away the nerve terminal is from its cell body. In contrast, the nerve terminal density of the dopaminergic neurons that project from the substantia nigra to the striatum was unaffected and was similar to that of the controls. The rank order of these presynaptic derangements at comparable distances from the respective cell bodies was found to be septohippocampal cholinergic > nucleus basalis cholinergic > locus coeruleus adrenergic > raphe serotonergic > nigrostriatal dopaminergic, which interestingly is similar to that observed in Alzheimer's disease. These results suggest that two complementary factors determine the susceptibility of brain projecting neurons to apoE deficiency: pathway-specific differences and the distance of the nerve terminals from their cell body.

Acetylcholinesterase↗

[Evaluation of health policy intervention on the community level--the "Neighborhood Coordination of Health and Social Care" Model Project in North Rhine-Westphalia].

Between October 1995 and December 1998 the pilot project 'Local Coordination of Health and Social Care' was conducted in 28 communities of the state of North Rhine-Westphalia. The project has been evaluated by two university research teams. The aim of the project was basically to establish new structures of health planning and coordination at the community level, in order to improve health reporting and health care as well as health promotion. To realize this aim round tables, working groups and project-offices were implemented in the communities. The evaluation was focused on the following question: What were the conditions (structures) and processes that influenced the project outcomes? Qualitative and quantitative methods were applied (interviews, standardised self-administered questionnaires, analyses of documents) to this end. Evaluation of structures showed that most communities succeeded in integrating relevant health policy actors into the newly created round tables and working groups. Working climate and achievements were evaluated favourably by most of the involved actors. All communities succeeded in developing and enacting recommendations for programmes, and about 40% of these programmes were implemented during the project. The probability of programme implementation was particularly high if the programme was based on reliable local data and if execution was effected only on the community level. The possibly beneficial effects on health care and welfare produced by the new programmes could not be assessed within the short project period. The paper concludes with a brief discussion of practical consequences for future health policy at community level.

Community Health Centers↗

The experience of Australian project leaders in encouraging practitioners to adopt research evidence in their clinical practice.

OBJECTIVE: This paper describes a qualitative program evaluation which sought to identify factors that either assist or impede the adoption of clinical evidence in everyday practice. DESIGN AND PARTICIPANTS: Thirteen Australian projects were funded in a competitive grant program to adopt innovative strategies to improve the uptake of research evidence in everyday clinical practice. Project leaders' reports were analysed to collate common themes related to 1) critical elements in successful application of research knowledge, 2) barriers to implementing evidence, and 3) lessons for other organisations that might implement a similar project. RESULTS: Despite the diversity of the methods used to establish projects and the range of topics and clinical settings, many similarities were identified in the perceived critical success elements, barriers, and lessons for adopting clinical evidence. Eighteen themes emerged across the data including: leadership support; key stakeholder involvement; practice changes; communication; resources; education of staff; evaluation of outcomes; consumers; knowledge gaps; adoption/implementing staff; access to knowledge; risk assessment; collaboration; effectiveness of clinical research evidence; structure/organisation; cultural barriers; previous experiences; and information technology. CONCLUSION: Leaders of projects to adopt evidence in clinical practice identified barriers, critical success elements and lessons that impacted on their projects. A range of influences on the adoption of evidence were identified, and this knowledge can be used to assist others undertaking similar projects.

Australia↗

Anatomical organization of forward fiber projections from area TE to perirhinal neurons representing visual long-term memory in monkeys.

A number of studies have shown that the perirhinal (PRh) cortex, which is part of the medial temporal lobe memory system, plays an important role in declarative long-term memory. The PRh cortex contains neurons that represent visual long-term memory. The aim of the present study is to characterize the anatomical organization of forward projections that mediate information flow from visual area TE to memory neurons in the PRh cortex. In monkeys performing a visual pair-association memory task, we conducted an extensive mapping of neuronal responses in the anteroventral part of area TE (TEav) and area 36 (A36) of the PRh cortex. Then, three retrograde tracers were separately injected into A36 and the distribution of retrograde labels in TEav was analyzed. We focused on the degree of divergent projections from TEav to memory neurons in A36, because the highly divergent nature of these forward fiber projections has been implicated in memory function. We found that the degree of divergent projection to memory neurons in A36 was smaller from the TEav neurons selective to learned pictures than from the nonselective TEav neurons. This result demonstrates that the anatomical difference (the divergence) correlates with the physiological difference (selectivity of TEav neurons to the learned pictures). Because the physiological difference is attributed to whether the projections are involved in information transmission required for memory neurons in A36, it can be speculated that the reduced divergent projection resulted from acquisition of visual long-term memory, possibly through retraction of the projecting axon collaterals.

Animals↗

Fate of the soma and dendrites of cord-projection central neurons after proximal and distal spinal axotomy: an intracellular dye injection study.

We used rat rubrospinal neurons as a model to study the soma-dendritic morphology of cord-projection neurons following spinal axonal injury. We examined lumbar-projection neurons following both upper cervical and lower thoracic axotomy to find out whether changes were dependent on the proximity of the lesion to the cell body. Axotomized neurons were marked with retrograde tracer and studied 4 and 8 weeks later with intracellular dye injection technique. Axotomy resulted in prominent shrinkage of their soma and relatively minor reduction of their dendritic spreads. The degree of soma shrinkage depended on both the duration of survival and the proximity of lesion. In addition, dendritic modification peaked 4 weeks following proximal lesion, which was also achieved 8 weeks following distal axotomy. Tractotomy at upper cervical and lower thoracic levels also allowed us to compare the effect of distal axotomy on cervical and lumbar-projection neurons. Results show that although cervical-projection neurons responded more quickly than lumbar-projecting ones, they however showed a similar degree of alteration in both their soma and dendrites 8 weeks following distal axotomy. In summary, cord-projection neurons survived 8 weeks following either upper cervical or lower thoracic axotomy with relatively intact dendritic features. Taken together, our data thus far suggest that cord-projection central neurons continue to integrate inputs and control supraspinal targets following spinal axotomy. The minor dendritic shrinkage within two months of spinal axotomy rejuvenates hopes for functional recovery if regeneration of their spinal axons can be achieved at least within this time frame.

Animals↗

The WISEWOMAN projects: lessons learned from three states.

BACKGROUND: The WISEWOMAN program provides chronic disease risk factor screening, lifestyle interventions, and referrals to financially disadvantaged women who participate in the National Breast and Cervical Cancer Early Detection Program (NBCCEDP). Three states (Arizona, Massachusetts, and North Carolina) participated in Phase One (1995-1998). METHODS: Using a case study approach, we reviewed documents and conducted telephone interviews to compare the three projects' design and execution. The interviews, carried out in mid-2002, involved a convenience sample of project coordinators, project directors, researchers, and one CDC project officer (n = 9). RESULTS: Many providers were overwhelmed by WISEWOMAN's research component and disliked its lack of flexibility. Researchers emphasized that high-quality evaluation requires resources and attention. Informants described the challenges of integrating WISEWOMAN with state BCCEDP programs that are in varying development stages and recommended changes in organizational culture and provider practices. Regarding implementation, informants emphasized the need for adequate and appropriate planning, buy-in, training, professional support, and outreach. Our sample also noted that WISEWOMAN projects tend to be labor intensive. CONCLUSIONS: WISEWOMAN projects face challenges of integrating clinical and lifestyle interventions, reaching beyond a focus on individuals, marshaling substantial resources, and introducing complex interventions into stretched healthcare environments. The three Phase One projects were deemed successful in reaching underserved women, developing a more comprehensive women's health model, strengthening linkages to primary healthcare, experimenting with innovative behavioral interventions, and tapping into women's roles as social support providers and family/community gatekeepers.

Adult↗

Bayesian projections: what are the effects of excluding data from younger age groups?

Bayesian age-period-cohort models are used increasingly to project cancer incidence and mortality rates. Data for younger age groups for which rates are low are often discarded from the analysis. The authors explored the effect of excluding these data, in terms of the precision and accuracy of projections, for selected cancer mortality data sets. Projections were made by using a generalized Bayesian age-period-cohort model. Smoothing was applied to each time scale to reduce random variation between adjacent parameter estimates. The sum of squared standardized residuals was used to assess the accuracy of projections, and 90% credible intervals were calculated to assess precision. For the data sets considered, inclusion of all age groups in the analysis provided more precise age-standardized and age-specific projections as well as more accurate age-specific projections for younger age groups. An overall improvement in the accuracy of age-standardized rates was demonstrated for males but not females, which may suggest that analysis of the full data set is beneficial when projecting cancer rates with strong cohort effects.

Adolescent↗

Convergent and complementary projections of the caudal paralaminar thalamic nuclei to rat temporal and insular cortex.

Thalamic nuclei adjacent to the medial geniculate body play a pivotal role in processing of sensory stimuli during emotional situations. These nuclei, which include the suprageniculate nucleus (SG), the posterior intralaminar nucleus (PIN), the peripeduncular nucleus (PP) and the medial division of the medial geniculate body (MGm), project to both cortex and amygdala, but target areas and the extent of the projection of individual nuclei are not known yet. The aim of the present study was to analyze the contribution of individual nuclei to the cortical projection with modern sensitive tracing techniques. Small injections of Miniruby or PHA-L were made into single thalamic nuclei. All thalamic nuclei have in common a projection into the upper portion of layer I of the temporal aspect of the cortical mantle. Furthermore, SG, PIN, MGm and PP each demonstrated a convergent projection to lower layer III and to layer IV of the ectorhinal and visceral cortex. Only MGm projects to layer VI of primary auditory and temporal association cortices. Within the perirhinal cortex zones of convergence and divergence exist. The present results demonstrate a differential thalamocortical projection of single thalamic nuclei to those cortical areas which are involved in the transmission of sensory signals to the amygdala via the thalamocortico-cortical pathway and to the hippocampus via the entorhinal cortex. The thalamic nuclei are thus in a position to activate the amygdala and to modulate the information flow of the thalamocortico-cortical pathway to both amygdala and hippocampus.

Animals↗

Projections from the lateral, basal and accessory basal nuclei of the amygdala to the perirhinal and postrhinal cortices in rat.

The projections from the amygdaloid complex to the hippocampus and surrounding cortex have a critical role in the formation of memories for emotionally arousing stimuli and in the spread of epileptic seizures. The present study investigated the organization of amygdaloid projections to the perirhinal and postrhinal cortices by injecting the anterograde tracer Phaseolus vulgaris leucoagglutinin into the different subdivisions of the lateral, basal or accessory basal nuclei of the amygdala in rat (n = 53). Analysis of immunohistochemically stained sections indicated that the medial and dorsolateral divisions of the lateral nucleus project heavily to layers I-V of caudal area 35 and to layers I-III of the rostroventral postrhinal cortex. The dorsolateral division also moderately innervates layer I of caudoventral area 36. The magnocellular division of the basal nucleus projects moderately to layers V and VI of rostral areas 35 and 36. The parvicellular division of the accessory basal nucleus projects moderately to layer V of caudal area 35, whereas the magnocellular division projects moderately to layers I and II of rostral area 35. Via these substantial, topographically organized projections, the amygdaloid complex might modulate information processing at different levels of the medial temporal lobe memory system.

Amygdala↗

Configuration, in serial reconstruction, of individual axons projecting from area V2 to V4 in the macaque monkey.

The detailed morphology of long extrinsically projecting axons in the neocortex has been difficult to investigate and is in fact poorly understood. Some data, based on extracellular injections of Phaseolus vulgaris leucoagglutinin (PHA-L), are available for individual axons projecting from area V1 to area V2 or MT. Like geniculocortical projections, axons projecting from area V1 to area MT are readily identifiable (they typically have a bistratified termination pattern and large terminal specializations and are of large caliber), but those projecting from area V1 to V2 are more variable. To provide a broader basis for interpreting constant and variable features of axon morphology, we used high-resolution serial section reconstruction to analyze small populations of PHA-L-labeled axons projecting from area V2 to V4. Reconstruction of 20 axons suggests that this system is variable in terms of overall configuration and laminar distribution. Most terminal arbors are located at the border between layers 3 and 4, but some remain entirely within layer 3 or 4, some target preferentially the superficial layers (1, 2, and 3A), and some have collaterals in layer 5 or, rarely, layer 6. Arbor size is fairly constant among the three visual cortical projections examined so far (typically about 200 microns in diameter). In area V4, however, axons frequently have three or four separate arbors, which branch divergently (in one instance, over 2.6 mm x 3.0 mm). These features may be correlated with aspects of the particular functional organization of area V4, such as coarse topography, large receptive field size, and modularity. Axonal variability may also denote differences, morphological or physiological, among neurons of origin in area V2.

Animals↗

Quantitative analysis of the corticocortical projections to the middle temporal area in the marmoset monkey: evolutionary and functional implications.

The connections of the middle temporal area (MT) were investigated in the marmoset, one of the smallest primates. Reflecting the predictions of studies that modeled cortical allometric growth and development, we found that in adult marmosets MT is connected to a more extensive network of cortical areas than in larger primates, including consistent connections with retrosplenial, cingulate, and parahippocampal areas and more widespread connections with temporal, frontal, and parietal areas. Quantitative analyses reveal that MT receives the majority of its afferents from other motion-sensitive areas in the temporal lobe and from the occipitoparietal transition areas, each of these regions containing approximately 30% of the projecting cells. Projections from the primary visual area (V1) and the second visual area (V2) account for approximately 20% of projecting neurons, whereas "ventral stream" and higher-order association areas form quantitatively minor projections. A relationship exists between the percentage of supragranular layer neurons forming the projections from different areas and their putative hierarchical rank. However, this relationship is clearer for projections from ventral stream areas than it is for projections from dorsal stream or frontal areas. These results provide the first quantitative data on the connections of MT and extend current understanding of the relationship between cortical anatomy and function in evolution.

Animals↗

Project quality rating by experts and practitioners: experience with Preffi 2.0 as a quality assessment instrument.

Preffi 2.0 is an evidence-based Dutch quality assessment instrument for health promotion interventions. It is mainly intended for both planning and assessing one's own projects but can also be used to assess other people's projects (external use). This article reports a study on the reliability of Preffi as an external quality assessment instrument. Preffi is used to assess quality at three levels: (i) specific criteria, (ii) clusters of criteria and (iii) entire projects. The study compared Preffi-based assessments of 20 projects by three practitioners with their intuitive assessments of the same projects and with assessments by three experts, which were to be used as external criteria. The intuitive assessments only related to the cluster and project levels. Our main hypothesis was that intuitive assessments by practitioners would be less reliable and accurate than their Preffi-based assessments and the experts' assessments. On the whole, we failed to confirm this hypothesis: the experts' assessments proved less reliable and accurate than the practitioners' intuitive and Preffi-based assessments and differed too much from each other to be used as external criteria. The Preffi-based assessments by the practitioners had an acceptable generalizability coefficient (G) and accuracy (standard error of measurement). At the level of the entire project, two assessors are needed to produce sufficiently reliable and accurate assessments, whereas three are needed for assessment at cluster level. The study also showed that different assessors use different perspectives and base their assessment on a variety of aspects. This was regarded as inevitable and even useful by the assessors themselves. Discussions between assessors are important to achieve consensus. The article suggests some improvements to Preffi to further increase its reliability.

Health Promotion↗

End-stage renal disease projections for Canada to 2005 using Poisson and Markov models.

BACKGROUND: End-stage renal disease (ESRD) incidence and prevalence are increasing in many countries worldwide. Due to the high cost of therapy, predicting future numbers of patients requiring dialysis and transplantation is necessary for health care planners. Projecting therapy-specific chronic disease prevalence is inherently problematic, and examples of suitable models and their application are sparse. When applied, rarely was the adequacy of such models evaluated. METHODS: We describe and illustrate a method for projecting therapy-specific ESRD prevalence in Canada for 1995-2005 using data obtained from the Canadian Organ Replacement Register. The projections combine the Poisson model for incidence rates and a Markov model for patient follow-up. Model adequacy is empirically validated by data-splitting. RESULTS: Large increases in ESRD prevalence are expected in Canada, with an average annual increase of 6.9% projected for 1995-2005. Upon validation, the projection model based on 1981-1987 data was able to predict 1994 prevalence within 1%, while projected therapy-specific prevalences closely approximated those observed. CONCLUSIONS: Therapy-specific ESRD prevalence was successfully projected using Poisson and Markov models. Where multistate prevalence forecasts are required, the method could be augmented for application to various other chronic diseases.

Adult↗