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Artificial neural network for the joint modelling of discrete cause-specific hazards.

OBJECTIVE: Artificial neural network (ANN) based regression methods have been introduced for modelling censored survival data to account for complex prognostic patterns. In the framework of ANN extensions of generalized linear models for survival data, PLANN is a partial logistic ANN, suitable for smoothed discrete hazard estimation as a function of time and covariates. An extension of PLANN for competing risks analysis (PLANNCR) is now proposed for discrete or grouped survival times, resorting to the multinomial likelihood. METHODS AND MATERIALS: PLANNCR is built by assigning input nodes to the explanatory variables with the time interval treated as an ordinal variable. The logistic function is used as activation for the hidden nodes of the network, whereas the softmax, which corresponds to the canonical link of generalized linear models for polytomous regression, is adopted for multiple output nodes, to provide a smoothed estimation of discrete conditional event probabilities for each event. The Kullback-Leibler distance is used as error function for the target vectors, amounting to half of the deviance of a multinomial logistic regression model. PLANNCR can jointly model non-linear, non-proportional and non-additive effects on cause-specific hazards (CSHs). The degree of smoothing is modulated by the number of hidden nodes and penalization of the error function (weight decay). Model optimisation is achieved by quasi-Newton algorithms, while non-linear cross-validation (NCV) and the Network Information Criterion (NIC) were adopted for model selection. PLANNCR was applied to data on 1793 women with primary invasive breast cancer, histologically N-, who underwent surgery at the Milan Cancer Institute between 1981 and 1986. RESULTS: Differential effects of covariates and time on the shape of the CSH for the three main failure causes, namely intra-breast tumor recurrences, distant metastases and contralateral breast cancer, have been enlightened. CONCLUSIONS: PLANNCR can be suitably adopted in an exploratory framework for a thorough evaluation of the disease dynamics in the presence of competing risks.

Adult↗

Kidney vending: opinions of the medical school students on this controversial issue.

BACKGROUND: In this era of globalization, in which different cultural and economic barriers are progressively abated, in the context of the development of rapid information networks such as the Internet, physicians are increasingly challenged by clinical and ethical questions. Kidney vending, banned in some countries, legal or tolerated in others, may be the prototype of the ethical aspects of health-care globalization. METHODS: To test the interest and the opinions of medical school students, a simulated case was proposed to students attending a seminar within the nephrology course fourth year of the Medical School of Torino, san Luigi): an Italian patient comes to the nephrologist's office asking for advice on the possibility to legally buy a kidney in a foreign country. The 43 students attending the lesson answered a semistructured questionnaire (15 boys, 28 girls, of median age 23 years). Attendance was within the usual standards (50 students inscribed per year). From the clinical point of view, 11.6% were favorable to kidney vending, 51.2% were contrary, 37.2% were uncertain. From the ethical point of view, no student was pro, 81.4% were contrary, and 18.6% were uncertain. The open comments underline the importance of patient self-determination and of informed consent. Similar opinions were recorded in a nonstructured question: "What should physician's attitude be, in the face of a choice he/she doesn't share?" CONCLUSION: Students' uncertainties and doubts underline the need to discuss ethical scenarios in the clinical teachings of the medical school.

Attitude to Health↗

The impact of loss of Medicaid on health service utilization among persons with HIV/AIDS in New York City.

OBJECTIVES: To examine predictors of losing Medicaid and the impact of losing Medicaid on health service utilization for persons living with HIV/AIDS. DESIGN: The data are from the Community Health Advisory and Information Network (CHAIN), an on-going longitudinal survey representative of adults with HIV/AIDS in NYC (N = 698) (1994-1997 data). Change of Medicaid coverage between survey waves was considered a "transition" yielding three groups: "no transition", "transition to insurance", and "transition to no insurance". METHODS: To determine predictors of transitions and the impact of transitions on health service utilization, multinomial logistic regression was used to compare the three groups. RESULTS: There were 114 transitions and 792 cases without transitions, with transitions decreasing over time. Thirty percent of transitions were from Medicaid to no insurance. Transitions to insurance were more likely among the employed and those with incomes over 15,000 US Dollar. Transitions to no insurance were more likely among AIDS cases, recent immigrants, and people less than 30-year-old. People in both transition groups were less likely than people who retained Medicaid to have experienced a life event in the pre-transition period. Those with transitions to insurance reported decreased hospital and drug treatment. People who became uninsured reported decreased use of routine and preventive care, decreased health information and advice and decreased use of private doctors and outpatient clinics. CONCLUSION: While the rate of transitions from Medicaid was relatively low, such transitions were associated with greater variability in quality of health care and greater difficulty accessing primary care among the uninsured.

Adult↗

Host-enhanced chemical indexing in technical databases.

Many files that index engineering, physics, or other technical literature contain references to chemical compounds. Complex chemical formulas in the title or abstract often contain special characters, for example, (,), [,], +, -, degrees, and %. Upper and lower case letters often are also included. A search of these formulas and symbols in the basic index is next to impossible because the terms in this field are usually parsed to all alphanumeric characters without sensitivity to case. It is possible for an online host to use a character-recognition algorithm to scan the title and abstract data for special characters or character strings and place them in a separate index field when such files are loaded. Such an algorithm has been designed by Fachinformationszentrun Energie, Physik, Mathematik GmbH in Karlsruhe, West Germany (FIZ Karlsruhe), the European service center of STN International, the scientific and technical information network. This algorithm recognizes and analyzes chemical formulas, material descriptions, alloys, and eutectic systems as well as nuclear reactions and dopings that appear in the title, abstract, or other fields. These character strings are converted into a standardized form and placed in a new field (the element terms field) which is supplied by the online host during the loading process. A checklist of allowed terms (symbols and chemical formulas) is used to prevent irrelevant terms from being mistaken for legitimate chemical symbols. For instance, the algorithm can recognize that CPU (central processing unit) is not a legitimate chemical formula. It is easy to demonstrate the utility this additional index supplies.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstracting and Indexing↗

Bridge populations in the spread of HIV/AIDS in Thailand.

OBJECTIVE: To determine the extent to which men provide a bridge population between commercial sex workers (CSW) and the general female population in Thailand. DESIGN: Sexual network and serological data were collected from a systematic quota sample of low income men and truckers during 1992 in three Thailand provinces. Completed sample size was 1075 men aged 17-45 years and 330 truckers. METHODS: Sexual network information was used to identify those men who have sex with both female CSW and non-CSW partners (the 'bridge population'). A new method was used for calculating the partner acquisition rate and to establish the potential number of women exposed to HIV via inconsistent condom use among the bridge population. RESULTS: Approximately 17% of men and 25% of truckers can be included in the bridge population. These men are more likely to be HIV-positive and to have had at least one other sexually transmitted infection in the past year (odds ratio, 2.2 and 3.4, respectively). Consistent condom use with CSW is less than 30%, and is less than 1% with non-CSW partners. As a result, 30 women in the general population were potentially exposed to HIV per 100 sexually active men in the last year:nine women each additional year. Younger men and truckers expose almost twice as many women to HIV; more female peers than wives are exposed. CONCLUSION: Bridge populations may be as important as "core groups' for the spread of HIV into the general Thai population. Young men and women are strategic intervention targets because they have more partners, are more likely to be in bridging networks, and are more receptive to condom use.

Acquired Immunodeficiency Syndrome↗

A randomized outpatient trial of a decision-support information technology tool.

BACKGROUND: Decision-support information technology is often adopted to improve clinical decision making, but it is rarely rigorously evaluated. Congress mandated the evaluation of Problem-Knowledge Couplers (PKC Corp, Burlington, Vt), a decision-support tool proposed for the Department of Defense's new health information network. METHODS: This was a patient-level randomized trial conducted at 2 military practices. A total of 936 patients were allocated to the intervention group and 966 to usual care. Couplers were applied before routine ambulatory clinic visits. The primary outcome was quality of care, which was assessed based on the total percentage of any of 24 health care quality process measures (opportunities to provide evidence-based care) that were fulfilled. Secondary outcomes included medical resources consumed within 60 days of enrollment and patient and provider satisfaction. RESULTS: There were 4639 health care opportunities (2374 in the Coupler group and 2265 in the usual-care group), with no difference in the proportion of opportunities fulfilled (33.9% vs 30.7%; P = .12). Although there was a modest improvement in performance on screening/preventive measures, it was offset by poorer performance on some measures of acute care. Coupler patients used more laboratory and pharmacy resources than usual-care patients (logarithmic mean difference, 71 dollars). No difference in patient satisfaction was observed between groups, and provider satisfaction was mixed. CONCLUSION: This study provides no strong evidence to support the utility of this decision-support tool, but it demonstrates the value of rigorous evaluation of decision-support information technology.

Adult↗

ATP-independent luminal oscillations and release of Ca2+ and H+ from mast cell secretory granules: implications for signal transduction.

InsP(3) is an important link in the intracellular information network. Previous observations show that activation of InsP(3)-receptor channels on the granular membrane can turn secretory granules into Ca(2+) oscillators that deliver periodic trains of Ca(2+) release to the cytosol (T. Nguyen, W. C. Chin, and P. Verdugo, 1998, Nature, 395:908-912; I. Quesada, W. C. Chin, J. Steed, P. Campos-Bedolla, and P. Verdugo, 2001, BIOPHYS: J. 80:2133-2139). Here we show that InsP(3) can also turn mast cell granules into proton oscillators. InsP(3)-induced intralumenal [H(+)] oscillations are ATP-independent, result from H(+)/K(+) exchange in the heparin matrix, and produce perigranular pH oscillations with the same frequency. These perigranular pH oscillations are in-phase with intralumenal [H(+)] but out-of-phase with the corresponding perigranular [Ca(2+)] oscillations. The low pH of the secretory compartment has critical implications in a broad range of intracellular processes. However, the association of proton release with InsP(3)-induced Ca(2+) signals, their similar periodic nature, and the sensitivity of important exocytic proteins to the joint action of Ca(2+) and pH strongly suggests that granules might encode a combined Ca(2+)/H(+) intracellular signal. A H(+)/Ca(2+) signal could significantly increase the specificity of the information sent by the granule by transmitting two frequency encoded messages targeted exclusively to proteins like calmodulin, annexins, or syncollin that are crucial for exocytosis and require specific combinations of [Ca(2+)] "and" pH for their action.

Adenosine Triphosphate↗

Functional relation between interneuron input and population activity in the rat hippocampal cornu ammonis 1 area.

Inhibitory interneurons are important components of the cornu ammonis 1 (CA1) network, as they are strategically positioned to control network information transfer. We investigated in detail synaptic input to individual CA1 interneurons (mainly basket and bistratified cells) after the local circuit was activated through the Schaffer-Commissural pathway and related this input to the population activity of the pyramidal cells. Synaptic responses were measured under whole-cell voltage clamp and population activity was determined from local field potentials. The synaptic input that was evoked in CA1 interneurons fell into two distinct groups. Disynaptic input with a long latency always started after the population spike with a mean latency of 3.0+/-0.3 ms (n=22) in respect to the peak of the population spike. This type of synaptic input to the interneurons was causally linked to the occurrence and amplitude of the population spike and most likely driven by CA1 pyramidal cells. Short-latency monosynaptic input occurred 0.8+/-0.2 ms (n=18) before the peak of the population spike. Its timing was strictly linked to the stimulus and showed significantly less jitter than long-latency input. In the absence of a population spike only short-latency input could be observed. Whether an interneuron receives direct monosynaptic Schaffer input or disynaptic input from the pyramidal cell population determines when that interneuron will be recruited in the network after Schaffer collateral stimulation. In addition, we found that the relation between the strength of the synaptic input and the population activity was different for the two types of input. Short-latency monosynaptic input showed large sensitivity to input changes at stimulus intensities that evoked little activity in the pyramidal cell population. In contrast, the amplitude of the long-latency disynaptic input to the interneurons closely reflected the population activity and increased gradually with stimulus intensity. Interneurons receiving the first type of input may expand the input sensitivity of the network, while interneurons receiving the second type could be involved in overall normalization of the output of the CA1 network. Our results underscore the importance of knowledge of the input to an interneuron for the understanding of its inhibitory role in the network.

Animals↗

Internet and healthcare in Brazil: the role of the Working Group for Healthcare (GT Saúde).

This paper introduces the GT Saúde initiative in Brazil. The group is part of the Brazilian Internet project, which goals are to depict how Internet can be useful to the society. The mission of the GT Saúde group is to foster Internet applications on the healthcare area. The main projects currently under development are presented: Multicom-21, using large bandwidth connections on telemedicine; the Unified Health Record, using Internet and smart-cards for a national minimum patient data set; the Brazilian Virtual Hospital, that presents a large amount of useful information and links for healthcare professionals and people in general; the National Healthcare Information Network (RNIS), that uses Internet as a medium for data exchange among the state secretaries and publishing statistics from the national healthcare system (SUS) for general public access; and finally the virtual university proposal, which uses Internet for education and is offering its first course on nutrition. The heterogeneity of the projects is meant and is part of the group's task, which is to cover the subject as widely as possible. Through this 'demonstration' projects the group is trying to prove the usefulness and benefits of using Internet technologies, even (or mainly) on a developing country with an inadequate healthcare situation. In its short existence the GT Saúde group has achieved several of its original goals. The most relevant accomplishments are: putting together different groups, eliciting synergy across the projects and encompassing a broad spectrum of applications (the 'demonstration factor').

Brazil↗

Luteinizing hormone-releasing hormone is a primary signaling molecule in the neuroimmune network.

The brain-pituitary-reproductive axis and the brain thymus-lymphoid axis are linked by an array of internal mechanisms of communication that use similar signals (neurotransmitters, peptides, growth factors, hormones) acting on similar recognition targets. Moreover, such communication networks form the basis and control each step and every level of reproductive physiology. This presentation highlights the extent to which endocrine, neural, glial, or immunologically competent cells may achieve their specific functions using common mechanisms, but employing them to different degrees. In particular, this work will focus on LHRH, the chief hormone orchestrating reproductive events. Within the thymus LHRH plays a unique role of immunomodulator, contributing to the sex-dependent changes in immune responsiveness during the estrous-menstrual cycle as well as pregnancy. From the recent cloning and sequencing of lymphocyte LHRH, the expression of LHRH receptor mRNA in lymphocyte, the transduction mechanisms involved, and the steroidogenic sensitivity of the intralymphocyte LHRH system. It would appear that this peptide may act as an immunological response modifier in the brain-pituitary-lymphoid-gonadal axis. The interplay between neuronal, endocrine, and immune compartments is further emphasized in the study of LHRH-astroglial interactions. Astrocytes are able to manufacture a wide variety of signaling agents and can secrete immunoregulatory molecules that influence immune cells, as well as the glial cells themselves. Astroglia and the immortalized hypothalamic LHRH (GT1-1) neurons communicate with an array of mechanisms, via soluble mediators as well as cell-to-cell contacts. Manipulation of astroglial-derived cytokines and nitric oxide (NO) in GT1-1 neuron-astroglia cocultures, underscores a potential cross-talk between different intra/inter-cellular mediators in the dynamic control of LHRH release. Further studies aimed to disclose at a biochemical and a molecular level such bidirectional, informative network will give us new insights into more general issues concerned with the malfunction of the neuroendocrine-immune axis.

Animals↗

Assessing the potential economic value of health information technology interventions in a community-based health network.

Health information professionals recognize the need to demonstrate that the benefits of health information technological (HIT) interventions outweigh their costs. However, such cost-benefit analyses are rarely conducted for HIT interventions, due in part to the lack of a standard methodology. In this study, we describe how the U.S. Public Health Service's guidelines for health economic analyses can be used to evaluate HIT interventions. This framework is described in the context of an economic analysis we are conducting for three HIT interventions to be implemented in a community-based health network caring for Medicaid beneficiaries in Durham County, North Carolina. At present, the 17,779 patients in our study cost Medicaid more than $5 million per month. In sensitivity analyses, we demonstrate that if our information intervention redirects just 10% of low-severity emergency room encounters to outpatient encounters, it will result in $12,523 of monthly savings to the local health system.

Biomedical Technology↗

[Contact allergies in medical occupations].

Based on reports in the literature, data from the information network of German dermatology centres (Informationsverbund Dermatologischer Kliniken) and the authors own findings, a review is presented on prevalence, clinical picture and causative agents of contact allergic dermatoses in health care professions. In 1991 the proportion of suspected occupational diseases in the health care professions (including hairdressers) represented by cases of dermatitis, as reported to the responsible insurance institution, reached 72% of the total for the year (7287 out of 10127). Every 20th to 40th case was recognized as an occupational dermatosis according to German law. Accurate figures on incidence are scarce; for dentists an incidence of 0.11% has been calculated. The risk of developing occupational hand eczema has been shown to be at least three times higher for nurses than for other so-called dry professions. For persons engaged in the personal care of the ill and the elderly, relevant occupational allergens were found to be benzalkonium chloride and aldehydes in disinfectants, as well as rubber accelerators such as thiuram mix. Latex contact urticaria has increasing significance for medical personnel, with prevalence rates of sensitization between 4.5% and 10.7%. Among physicians, contact allergies to thiuram mix were found to be dominant (12.9%). For surgeons and orthopaedic surgeons, methyl methacrylate as a constituent of bone cement is of great importance. Various esters of acrylic acid and methacrylic acid are important sensitizers in the dental professions, particularly in heavily exposed dental laboratory technicians. Only a few gloves protect against these types of sensitizers. Sensitizations by medicaments can be avoided in most cases by reducing direct skin contact, as practiced with penicillin or ispaghula powder. Strategies of prevention include information of atopics regarding the increase in occupational dermatitis, the regular use of barrier creams, intensive skin care after work and avoidance of irritants and allergens wherever possible.

Cross-Sectional Studies↗

Patch test results with the metalworking fluid series of the German Contact Dermatitis Research Group (DKG).

Based on the information of the interdisciplinary task force on allergy diagnostics in the metal branch, in 2001, the German Contact Dermatitis Research Group (DKG) compiled two metalworking fluid (MWF) test series with currently and previously used components, respectively. After 2 years of patch testing, we present results obtained with these series, based on data of the Information Network of Departments of Dermatology (IVDK). 251 metalworkers who were patch tested because of suspected MWF dermatitis in 2002 and 2003 were included in this retrospective data analysis. Of these, 206 were tested with the current MWF series and 155 with the historical MWF series. Among the current MWF allergens, monoethanolamine ranked 1st with 11.6% positive reactions. Diethanolamine (3.0%), triethanolamine (1.1%), and diglycolamine (1.9%) elicited positive reactions far less frequently. Allergic reactions to p-aminoazobenzene were frequently observed (6.0%), but the relevance of these reactions is still obscure. Positive reactions to biocides ranged from 4.5% for Bioban CS 1135 to 0.5% for iodopropynyl butylcarbamate and 2-phenoxyethanol. Concomitant reactions to formaldehyde, which caused positive reactions in 3.3%, and formaldehyde releasers occurred to varying extents without conclusive pattern. No positive reactions were seen to dibutyl phthalate, di-2-ethylhexyl phthalate, tricresyl phosphate, isopropyl myristate or benzotriazole. With the historical MWF test series, positive reactions to methyldibromo glutaronitrile (MDBGN) were observed most frequently. However, sensitization via allergen sources other than MWF seems likely, as MDBGN, during the study period, has been one of the most frequent preservative allergens in cosmetics and body care products. Other historical MWF allergens comprised morpholinyl mercaptobenzothiazole (3.3%), benzisothiazolinone (BIT; 2.0%) and Bioban P 1487(1.3%). BIT is currently used in MWF again, so it was shifted to the current MWF test series. As decreasing reaction frequencies to former MWF allergens that are no longer used can be expected, the historical series should be re-evaluated after some years. The test series with current MWF allergens has to be kept up-to-date based on information from industry and to be kept concise by eliminating test substances which never cause positive reactions.

Adolescent↗

Contact allergies in healthcare workers. Results from the IVDK.

Healthcare workers often suffer from occupational skin disease frequently caused by allergic sensitization. Therefore the patch-test results and important patient history items of 31,849 patients recorded between 1992 and 1995 in the 24 allergy departments participating in the Information Network of Departments of Dermatology (IVDK) were evaluated. Significantly increased sensitization rates common to the healthcare sector as a whole were found for the vaccine preservative thiomersal (12.6% vs. 4.9%), the surface and instrument disinfectants glutardialdehyde (9.9% vs. 2.6%), formaldehyde (3.6% vs. 2.1%) and glyoxal (4.2% vs. 1.4%), and for the compounds of the thiuram mix (6.7% vs. 2.6%) present in protective gloves. Formaldehyde seems to lose its importance, but glyoxal must be added to the list of occupational allergens in the healthcare sector. In addition, occupation-specific sensitization was observed, with fragrances in massage therapists (16.1% vs. 10.6%) and nurses (13.8% vs. 11.4%), as well as with methacrylates in dental technicians. The often assumed importance of drugs as type-IV allergens was not confirmed, at least in terms of quantity. The identification of subgroups of increased risk and of occupation-specific allergens could be the basis of targeted preventive action in the healthcare sector.

Adult↗

Validation of an electronic, population-based prescription database.

BACKGROUND: The Drug Programs Information Network (DPIN), Manitoba's (Canada) new electronic prescription database, is a valuable data source for pharmacoepidemiologic research. Pharmacies are required to submit to the DPIN all prescriptions for Pharmacare, the province's drug insurance plan, but submission of prescriptions for social assistance recipients and treaty status Indians is discretionary. OBJECTIVE: The completeness of the DPIN prescription database was assessed to determine whether treaty status Indians and social assistance recipients were underrepresented. DESIGN: Prescriptions dispensed during March 13-17, 1995, in a stratified sample of Manitoba pharmacies were linked to DPIN by prescription number to determine the proportions submitted for Indian Affairs, Social Services, and Pharmacare recipients. Pharmacare records in the DPIN were compared with original pharmacy records to evaluate data accuracy. RESULTS: Of 2196 Indian Affairs and 1879 Social Services prescriptions dispensed in 58 pharmacies, a corresponding prescription was found in the DPIN for 79.7% (98% CI 78.0% to 81.4%) and 90.1% (98% CI 88.8% to 91.4%) of prescriptions, respectively. These proportions were significantly lower than the estimated proportion of Pharmacare prescriptions submitted (93%, 98% CI 92.4% to 93.6%). Ninety-two percent of 8012 DPIN Pharmacare prescriptions matched the original prescription on the drug name, quantity, and days' supply. CONCLUSIONS: This study established that the DPIN is a valid and reliable data source for studying prescription use among the majority of Manitoban residents. However, the DPIN database has differential validity and underrepresents prescriptions dispensed for the aboriginal population.

Databases, Factual↗

Some tools for the diffusion of biomedical information using research networks.

Research and academic computer networks provide e-mail and other services to all members of participating institutions. Their usage by biomedical researchers and clinicians is still limited because of several reasons, including limited awareness of the available network resources. An increased use of these networks within the biomedical community would allow fast, effective communications and convenient remote access to information sources. As an example and pilot study, we prepared two network tools to make some information services maintained by our institution also accessible through e-mail. Both tools were implemented using PMDF e-mail software on a DEC MicroVAX connected to the Italian academic and research network (GARR), which is linked to the U.S. Internet. A network server takes care of automatic distribution of documents (files) reporting results of an oncology research/education project. An information server provides for semiautomated support of a consulting service on use of drugs. The feasibility of implementing these tools, based on existing software, further illustrates the potential usefulness of research computer networks for the dissemination of biomedical information.

Computer Communication Networks↗

International infectious disease law: revision of the World Health Organization's International Health Regulations.

The International Health Regulations (IHR), the only global regulations for infectious disease control, have not been significantly changed since they were first issued in 1951. The World Health Organization (WHO) is currently engaged in a process to modernize the IHR. This article reviews WHO's draft revised IHR and recommends new reforms to improve global health, which include (1) a robust mission, emphasizing the WHO's core public health purposes, functions, and essential services; (2) broad scope, flexibly covering diverse health threats; (3) global surveillance, developing informational networks of official and unofficial data sources; (4) national public health systems, setting performance criteria, measuring outcomes, and holding states accountable; (5) human rights protection, setting science-based standards and fair procedures; and (6) good governance, adopting the principles of fairness, objectivity, and transparency. The WHO should ensure state compliance with health norms and generous economic and technical assistance to poorer countries. An important issue for the international community is how sovereign countries can join together to make global health work for everyone, the poor and the wealthy alike.

Communicable Disease Control↗

Psychosocial predictors of service utilization among Cuban-American elders.

The utilization of service by Cuban-American elders is studied in light of the informal network and sociodemographic hypotheses extant in the current literature. In addition, the effects of psychological variables are assessed. The data from questionnaires administered to 88 Cuban-American elderly give partial support for findings previously obtained with elderly subjects. However, the results suggest that unidimensional hypotheses are inadequate for explaining service utilization. More complex models that account for multidimensional interactions between population-specific variables must be developed to guide future research and practice.

Aged↗