A simplified low-cost phantom for image quality assessment of dental cone beam computed tomography unit.

INTRODUCTION: A standardised testing protocol for evaluation of a wide range of dental cone beam computed tomography (CBCT) performance and image quality (IQ) parameters is still limited and commercially available testing tool is unaffordable by some centres. This study aims to assess the performance of a low-cost fabricated phantom for image quality assessment (IQA) of digital CBCT unit. METHODS: A customised polymethyl methacrylate (PMMA) cylindrical phantom was developed for performance evaluation of Planmeca ProMax 3D Mid digital dental CBCT unit. The fabricated phantom consists of four different layers for testing specific IQ parameters such as CT number accuracy and uniformity, noise and CT number linearity. The phantom was scanned using common scanning protocols in clinical routine (90.0 kV, 8.0 mA and 13.6 s). In region-of-interest (ROI) analysis, the mean CT numbers (in Hounsfield unit, HU) and noise for water and air were determined and compared with the reference values (0 HU for water and -1000 HU for air). For linearity test, the correlation between the measured HU of different inserts with their density was studied. RESULTS: The average CT number were -994.1 HU and -2.4 HU, for air and water, respectively and the differences were within the recommended acceptable limit. The linearity test showed a strong positive correlation (R2 = 0.9693) between the measured HU and their densities. CONCLUSION: The fabricated IQ phantom serves as a simple and affordable testing tool for digital dental CBCT imaging.

Conceptual risk assessment of mosquito population modification gene-drive systems to control malaria transmission: preliminary hazards list workshops.

The field-testing and eventual adoption of genetically-engineered mosquitoes (GEMs) to control vector-borne pathogen transmission will require them meeting safety criteria specified by regulatory authorities in regions where the technology is being considered for use and other locales that might be impacted. Preliminary risk considerations by researchers and developers may be useful for planning the baseline data collection and field research used to address the anticipated safety concerns. Part of this process is to identify potential hazards (defined as the inherent ability of an entity to cause harm) and their harms, and then chart the pathways to harm and evaluate their probability as part of a risk assessment. The University of California Malaria Initiative (UCMI) participated in a series of workshops held to identify potential hazards specific to mosquito population modification strains carrying gene-drive systems coupled to anti-parasite effector genes and their use in a hypothetical island field trial. The hazards identified were placed within the broader context of previous efforts discussed in the scientific literature. Five risk areas were considered i) pathogens, infections and diseases, and the impacts of GEMs on human and animal health, ii) invasiveness and persistence of GEMs, and interactions of GEMs with target organisms, iii) interactions of GEMs with non-target organisms including horizontal gene transfer, iv) impacts of techniques used for the management of GEMs and v) evolutionary and stability considerations. A preliminary hazards list (PHL) was developed and is made available here. This PHL is useful for internal project risk evaluation and is available to regulators at prospective field sites. UCMI project scientists affirm that the subsequent processes associated with the comprehensive risk assessment for the application of this technology should be driven by the stakeholders at the proposed field site and areas that could be affected by this intervention strategy.

Radiological and Dosimetric Evaluation of Biomaterial Composite Phantoms with High Energy Photons and Electrons.

ABSTRACT: The current study was undertaken to investigate the radiological and dosimetric parameters of natural product-based composite (SPI/NaOH/IA-PAE/ Rhizophora spp .) phantoms. The radiological properties of the phantoms were measured at different gamma energies from Compton scatter of photons through angles of 0, 30, 45, 60, 75, and 90 degrees. Ionization chamber (IC) and Gafchromic EBT3 film dosimeters were employed to evaluate the dosimetric characteristics for photons (6-10 MV) and electrons (6-15 MeV). Radiological property results of the composite phantoms were consistent with good quality compared to those of solid water phantoms and theoretical values of water. Photon beam quality index of the SPI15 phantom with p-values of 0.071 and 0.073 exhibited insignificant changes. In addition, good agreement was found between PDD curves measured with IC and Gafchromic EBT3 film for both photons and electrons. The computed therapeutic and half-value depth ranges matched within the limits and are similar to those of water and solid water phantoms. Therefore, the radiological and dosimetric parameters of the studied composite phantom permit its use in the selection of convenient tissue- and water-equivalent phantom material for medical applications.

Assessment of root-specific promoters in banana and tobacco and identification of a banana TIP2 promoter with strong root activity.

Genetic modification is one possible strategy to generate bananas (Musa spp.) with resistance to the soil-borne pathogen causing Fusarium wilt. The availability of banana root-specific promoters to target transgene expression to the sites of infection would be beneficial. We have assessed 18 promoter sequences derived from a range of plant species for their expression profiles in banana tissues to identify those with root-specific activity. Promoter sequences were isolated and fused to the ß-glucuronidase (GUS) gene to assess their expression levels and tissue specificity in both banana and the model plant tobacco. Two heterologous promoters conferring high root expression levels in banana were identified, including a ß-glucosidase 1 (GLU1) promoter from maize and the RB7-type tonoplast intrinsic protein (TIP)-2 promoter from strawberry. Further, a novel Musa TIP2-2 promoter sequence was isolated and characterized which, when fused to the GUS gene, conferred very high GUS expression levels in banana roots. These promoters will expand the options for the control of gene expression in genetically modified bananas, providing a tool to develop plants with resistance not only to soil-borne diseases such as Fusarium wilt, but also for the improvement of other traits, such as nematode resistance, nutrition or abiotic stress resistance.

Beyond the eye: Kynurenine pathway impairment causes midgut homeostasis dysfunction and survival and reproductive costs in blood-feeding mosquitoes.

Insect ommochrome biosynthesis pathways metabolize tryptophan to generate eye-color pigments and wild-type alleles of pathway genes are useful phenotypic markers in transgenesis studies. Pleiotropic effects of mutations in some genes exert a load on both survival and reproductive success in blood-feeding species. Here, we investigated the challenges imposed on mosquitoes by the increase of tryptophan metabolites resulting from blood meal digestion and the impact of disruptions of the ommochrome biosynthesis pathway. Female mosquitoes with spontaneous and induced mutations in the orthologs of the genes encoding kynurenine hydroxylase in Aedes aegypti, Anopheles stephensi and Culex quinquefasciatus exhibited impaired survival and reproductive phenotypes that varied in type and severity among the species. A compromised midgut permeability barrier function was also observed in An. stephensi. Surprisingly, mutant mosquitoes displayed an increase in microbiota compared to controls that was not accompanied by a general induction of immune genes. Antibiotic treatment rescued some deleterious traits implicating a role for the kynurenine pathway (KP) in midgut homeostasis. Supplemental xanthurenic acid, a KP end-product, rescued lethality and limited microbiota proliferation in Ae. aegypti. These data implicate the KP in the regulation of the host/microbiota interface. These pleiotropic effects on mosquito physiology are important in the development of genetic strategies targeting vector mosquitoes.

Psychological intervention, antipsychotic medication or a combined treatment for adolescents with a first episode of psychosis: the MAPS feasibility three-arm RCT.

BACKGROUND: When psychosis emerges in young people there is a risk of poorer outcomes, and access to evidence-based treatments is paramount. The current evidence base is limited. Antipsychotic medications show only a small benefit over placebo, but young people experience more side effects than adults. There is sparse evidence for psychological intervention. Research is needed to determine the clinical effectiveness and cost-effectiveness of psychological intervention versus antipsychotic medication versus a combined treatment for adolescents with psychosis. OBJECTIVES: The objective of Managing Adolescent first-episode Psychosis: a feasibility Study (MAPS) was to determine the feasibility of conducting a definitive trial to answer the question of clinical effectiveness and cost-effectiveness of these three treatment options. DESIGN: This was a prospective, randomised, open-blinded, evaluation feasibility trial with a single blind. Participants were allocated 1 : 1 : 1 to receive antipsychotic medication, psychological intervention or a combination of both. A thematic qualitative study explored the acceptability and feasibility of the trial. SETTING: Early intervention in psychosis services and child and adolescent mental health services in Manchester, Oxford, Lancashire, Sussex, Birmingham, Norfolk and Suffolk, and Northumberland, Tyne and Wear. PARTICIPANTS: People aged 14-18 years experiencing a first episode of psychosis either with an International Classification of Diseases, Tenth Revision, schizophrenia spectrum diagnosis or meeting the entry criteria for early intervention in psychosis who had not received antipsychotic medication or psychological intervention within the last 3 months. INTERVENTIONS: Psychological intervention involved up to 26 hours of cognitive-behavioural therapy and six family intervention sessions over 6 months, with up to four booster sessions. Antipsychotic medication was prescribed by the participant's psychiatrist in line with usual practice. Combined treatment was a combination of psychological intervention and antipsychotic medication. MAIN OUTCOME MEASURES: The primary outcome was feasibility (recruitment, treatment adherence and retention). We used a three-stage progression criterion to determine feasibility. Secondary outcomes were psychosis symptoms, recovery, anxiety and depression, social and educational/occupational functioning, drug and alcohol use, health economics, adverse/metabolic side effects and adverse/serious adverse events. RESULTS: We recruited 61 out of 90 (67.8%; amber zone) potential participants (psychological intervention, n = 18; antipsychotic medication, n = 22; combined treatment, n = 21). Retention to follow-up was 51 out of 61 participants (83.6%; green zone). In the psychological intervention arm and the combined treatment arm, 32 out of 39 (82.1%) participants received six or more sessions of cognitive-behavioural therapy (green zone). In the combined treatment arm and the antipsychotic medication arm, 28 out of 43 (65.1%) participants received antipsychotic medication for 6 consecutive weeks (amber zone). There were no serious adverse events related to the trial and one related adverse event. Overall, the number of completed secondary outcome measures, including health economics, was small. LIMITATIONS: Medication adherence was determined by clinician report, which can be biased. The response to secondary outcomes was low, including health economics. The small sample size obtained means that the study lacked statistical power and there will be considerable uncertainty regarding estimates of treatment effects. CONCLUSIONS: It is feasible to conduct a trial comparing psychological intervention with antipsychotic medication and a combination treatment in young people with psychosis with some adaptations to the design, including adaptations to collection of health economic data to determine cost-effectiveness. FUTURE WORK: An adequately powered definitive trial is required to provide robust evidence. TRIAL REGISTRATION: Current Controlled Trials ISRCTN80567433. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 4. See the NIHR Journals Library website for further project information.

Psychosis is a mental health problem that can involve hearing, seeing or believing things that others do not. Although many young people who experience psychosis recover well from their first episode of psychosis, others can have more serious, longer-lasting problems. There has not been a large amount of research into the treatment of psychosis in young people; therefore, it is important to test different treatments against each other in clinical trials. 'Feasibility' trials, such as the one we carried out [Managing Adolescent first-episode Psychosis: a feasibility Study (MAPS)], test whether or not it is possible to run larger trials. MAPS was a small trial that was run in seven locations in the UK. People who were aged 14­18 years and experiencing psychosis were able to take part. Each participant was randomly assigned to receive psychological treatment (cognitive­behavioural therapy and optional family therapy), antipsychotic medication or a combination of both. All of the participants met with a trial research assistant three times for assessments about well-being and symptoms. Some clinicians, participants and family members were interviewed about their opinions of the trial and treatments. The trial also had patient and public involvement; service user researchers were involved in design, interview data collection, analysis and report writing. Sixty-one young people took part in MAPS, which was around 68% of our target number. In total, 84% completed the assessments with research assistants. The results showed that, overall, all treatments were acceptable to young people and their family members. However, a higher percentage of young people actually received the 'minimum dose' of psychological treatment than the 'minimum dose' of antipsychotic medication (82% vs. 65%). Results showed that it was possible to run a larger trial such as this. However, some changes would be required to run a larger trial, such as location (focusing on urban areas with well established early intervention in psychosis teams), increasing involvement of psychiatrists and increasing the age limit for participation to 25 years.

Metabolic syndrome in rural Australia: An opportunity for primary health care.

OBJECTIVE: To measure the impact of a 6-month home-based behaviour change intervention on reducing the risk of chronic disease as determined by metabolic syndrome status and cardiovascular risk score, and discuss implications for primary care in rural areas. DESIGN: A two-arm randomised controlled trial of rural adults. SETTING: The rural town of Albany in the Great Southern region of Western Australia. PARTICIPANTS: Participants (n = 401) aged 50-69 years who were classified with or at risk of metabolic syndrome and randomly assigned to intervention (n = 201) or waitlisted control (n = 200) group. INTERVENTIONS: A 6-month intervention program incorporating goal setting, self-monitoring and feedback, with motivational interviewing was conducted. MAIN OUTCOME MEASURES: Change in metabolic syndrome status and cardiovascular risk. RESULTS: Significant improvements in metabolic syndrome status and cardiovascular disease risk score (-0.82) were observed for the intervention group relative to control group from baseline to post-test. CONCLUSION: This home-based physical activity and nutrition intervention reduced participants' risk of experiencing a cardiovascular event in the next 5 years by 1%. Incorporating such prevention orientated approaches in primary care might assist in reducing the burden of long-term chronic diseases. However, for realistic application in this setting, hurdles such as current national health billing system and availability of resources will need to be considered.

Assessment and optimization of rolling circle amplification protocols for the detection and characterization of badnaviruses.

The genus Badnavirus is characterized by members that are genetically and serologically heterogeneous which presents challenges for their detection and characterization. The presence of integrated badnavirus-like sequences in some host species further complicates detection using PCR-based protocols. To address these challenges, we have assessed and optimized various RCA protocols including random-primed RCA (RP-RCA), primer-spiked random-primed RCA (primer-spiked RP-RCA), directed RCA (D-RCA) and specific-primed RCA (SP-RCA). Using Dioscorea bacilliform AL virus (DBALV) as an example, we demonstrate that viral DNA amplified using the optimized D-RCA and SP-RCA protocols showed an 85-fold increase in badnavirus NGS reads compared with RP-RCA. The optimized RCA techniques described here were used to detect a range of badnaviruses infecting banana, sugar cane, taro and yam demonstrating the utility of RCA for detection of diverse badnaviruses infecting a variety of host plant species.

A common brain network links development, aging, and vulnerability to disease.

Several theories link processes of development and aging in humans. In neuroscience, one model posits for instance that healthy age-related brain degeneration mirrors development, with the areas of the brain thought to develop later also degenerating earlier. However, intrinsic evidence for such a link between healthy aging and development in brain structure remains elusive. Here, we show that a data-driven analysis of brain structural variation across 484 healthy participants (8-85 y) reveals a largely--but not only--transmodal network whose lifespan pattern of age-related change intrinsically supports this model of mirroring development and aging. We further demonstrate that this network of brain regions, which develops relatively late during adolescence and shows accelerated degeneration in old age compared with the rest of the brain, characterizes areas of heightened vulnerability to unhealthy developmental and aging processes, as exemplified by schizophrenia and Alzheimer's disease, respectively. Specifically, this network, while derived solely from healthy subjects, spatially recapitulates the pattern of brain abnormalities observed in both schizophrenia and Alzheimer's disease. This network is further associated in our large-scale healthy population with intellectual ability and episodic memory, whose impairment contributes to key symptoms of schizophrenia and Alzheimer's disease. Taken together, our results suggest that the common spatial pattern of abnormalities observed in these two disorders, which emerge at opposite ends of the life spectrum, might be influenced by the timing of their separate and distinct pathological processes in disrupting healthy cerebral development and aging, respectively.

Development of a novel mouse model of severe glucose-6-phosphate dehydrogenase (G6PD)-deficiency for in vitro and in vivo assessment of hemolytic toxicity to red blood cells.

Studies of hemolytic agents on G6PD-deficient subjects have been extensively performed on red blood cells obtained from donors, only using in vitro methods. However, there has been no adequate G6PD-deficient animal model for in vivo assessment of potentially hemolytic agents. The objective of this study is to establish a novel mouse model of severe G6PD-deficiency, with high susceptibility to hemolytic damage upon oxidative agents. To create this model, G6PD mutant Gpdx allele was introduced into the C57L/J mouse strain background by breeding program. The hemolytic toxicity of naphthalene and its metabolite α-naphthol on G6PD-deficient red blood cells was evaluated. Our data showed that the F2 homozygous Gpdx mutant with C57L/J background exhibiting the G6PD activity was 0.9±0.1 U/g Hb, level similar to those of G6PD deficiency in human. A significantly negative correlation was demonstrated between GSH percentage reduction and G6PD activity (r=-0.51, p<0.001) upon challenge of the red blood cells with alpha-naphthol in vitro. Similar correlation was also found between GSSG elevation and G6PD activity. Our in vivo studies showed that the administration of naphthalene at 250 mg/kg inflicted significant oxidative damage to the G6PD-deficient mice, as illustrated by the decrease of the GSH-to-GSSG ratio (by 34.2%, p=0.005) and the increase of the methemoglobin level (by 1.9 fold, p<0.001). Hemolytic anemia was also found in G6PD-deficient mice at this dosage of naphthalene. In summary, this novel mouse model could be utilized as a screening platform to more accurately determine the hemolytic toxicity of pharmacological agents on G6PD-deficient subjects.

Complete mtDNA genomes of Anopheles darlingi and an approach to anopheline divergence time.

BACKGROUND: The complete sequences of the mitochondrial genomes (mtDNA) of members of the northern and southern genotypes of Anopheles (Nyssorhynchus) darlingi were used for comparative studies to estimate the time to the most recent common ancestor for modern anophelines, to evaluate differentiation within this taxon, and to seek evidence of incipient speciation. METHODS: The mtDNAs were sequenced from mosquitoes from Belize and Brazil and comparative analyses of structure and base composition, among others, were performed. A maximum likelihood approach linked with phylogenetic information was employed to detect evidence of selection and a Bayesian approach was used to date the split between the subgenus Nyssorhynchus and other Anopheles subgenera. RESULTS: The comparison of mtDNA sequences within the Anopheles darlingi taxon does not provide sufficient resolution to establish different units of speciation within the species. In addition, no evidence of positive selection in any protein-coding gene of the mtDNA was detected, and purifying selection likely is the basis for this lack of diversity. Bayesian analysis supports the conclusion that the most recent ancestor of Nyssorhynchus and Anopheles+Cellia was extant ~94 million years ago. CONCLUSION: Analyses of mtDNA genomes of Anopheles darlingi do not provide support for speciation in the taxon. The dates estimated for divergence among the anopheline groups tested is in agreement with the geological split of western Gondwana (95 mya), and provides additional support for explaining the absence of Cellia in the New World, and Nyssorhynchus in the Afro-Eurasian continents.

Utilização de informações para controle social: o caso do Conselho do Distrito Sanitário III do Recife / Social control information use: the case of the health Council of the Sanitary District III, Recife, Brazil

Pesquisas prévias sobre conselhos de saúde revelaram obstáculos ao desempenho desses colegiados no exercício do controle social, tais como: não disponibilização de informações adequadas pelos gestores, dificuldades de acesso a informações de saúde e falta de capacidade de compreensão dessas informações por parte dos conselheiros usuários e trabalhadores em saúde. Um estudo de caso do Distrito Sanitário III do Recife, contemplando o período de outubro 2003 a julho 2005, revelou que havia grande disponibilidade de informações no Distrito, assim como na Secretaria Municipal de Saúde e nos sistemas do Departamento de Informática do Sistema Único de Saúde (DATASUS). Mesmo assim, não eram utilizadas pelos conselheiros por falta de conhecimento, capacidade e ou interesse, ou ainda, dificuldades de acesso à internet. A maioria dos representantes de usuários, por exercerem lideranças comunitárias, viam a si próprios como fiscais da rede de saúde, havendo grande dependência do distrito e preferência por se discutir temas pontuais e imediatos. O uso de linguagem técnica pelo Distrito dificultava a compreensão das informações, impedindo questionamentos e debates. Através da comparação com resultados de pesquisas anteriores levanta-se algumas questões quanto ao modelo de participação popular do SUS.

Radon exposure assessment and dosimetry applied to epidemiology and risk estimation.

Epidemiological studies of underground miners provide the primary basis for radon risk estimates for indoor exposures as well as mine exposures. A major source of uncertainty in these risk estimates is the uncertainty in radon progeny exposure estimates for the miners. Often the exposure information is very incomplete, and exposure estimation must rely on interpolations, extrapolations and reconstruction of mining conditions decades before, which might differ markedly from those in more recent times. Many of the measurements that were carried out-commonly for health protection purposes-are not likely to be representative of actual exposures. Early monitoring was often of radon gas rather than of the progeny, so that quantifying exposure requires an estimate of the equilibrium fraction under the conditions existing at the time of the reported measurement. In addition to the uncertainty in radon progeny exposure, doses from gamma radiation, inhaled radioactive dust, and thoron progeny have historically been neglected. These may induce a systematic bias in risk estimates and add to the overall uncertainty in risk estimates derived from the miner studies. Unlike other radiogenic cancer risk estimates, numerical risk estimates derived for radon from epidemiology are usually expressed as a risk per unit exposure rather than as a risk per unit dose to a target tissue. Nevertheless, dosimetric considerations are important when trying to compare risks under different exposure conditions, e.g. in mines and homes. A recent comparative assessment of exposure conditions indicates that, for equal radon progeny exposures, the dose in homes is about the same as in mines. Thus, neglecting other possible differences, such as the presence in mines of other potential airborne carcinogens, the risk per unit progeny exposure should be about the same for indoor exposures as observed in miners. Results of case-control studies of lung cancer incidence in homes monitored for radon are reasonably consistent with what would be projected from miner studies. Measurements of exposure in these indoor case-control studies rely on different types of detectors than those used in mines, and the estimates of exposure are again a major source of uncertainty in these studies.

The legal and clinical implications of crushing tablet medication.

It has recently been estimated that 75 per cent of all older patients will fail to comply with their medication regimes at some point during their hospital stay (Wright, 2002). Crushing tablets or opening capsules in order to assist a patient with swallowing difficulties appears to be a widespread activity. There may be times when tablets will need to be crushed in order to deliver essential drug therapy; this should only be done as a last resort. Crushing tablets is a practice that has the potential to endanger patient safety and contravene legal and professional requirements.

Implementing a Multi-Agency Needs Assessment in a Secure Adolescent Unit.

BACKGROUND: Process issues in relation to the introduction of standardised needs assessments have traditionally received little attention. METHOD: Descriptive approach to the theoretical and practical aspects of the development of an assessment process using a structured instrument, the clinical version of the Salford Needs Assessment Schedule for Adolescents (SNASA). The context for this was child and adolescent mental health liaison with a social services secure unit for adolescent boys. RESULTS: The use of a structured process model facilitated the implementation process enormously. Positive outcomes were experienced by participating staff at different levels within agency hierarchies and by the wider professional network. CONCLUSIONS: Successful implementation and continuing use of structured assessments and other instruments in multi-agency settings requires attention to process issues. Such attention needs to be concerted and ongoing. Within child and adolescent mental health settings such an approach may be helpful beyond the field of secure adolescent care.

Eating attitudes in English secondary school students: influences of ethnicity, gender, mood, and social class.

OBJECTIVE: To examine the effects of ethnicity, gender, socioeconomic position, self-esteem, and emotion on eating attitudes in adolescents. METHOD: Questionnaire survey of 722 students in two English schools, using Eating Attitude Test-26 (EAT), Rosenberg Self-Esteem Scale, and Angold vMood and Feeling instruments. RESULTS: EAT scores were significantly higher for Asians and Muslims and for mixed-race subjects than for White or African Caribbean subjects (p =.003). Adjusted odds ratios for having a very high EAT score (>20) were 2.4 (95% confidence interval [CI] 1.0-6.0) in Asians and Muslims and 2.9 (95% CI 1.3-18.6) in mixed-race subjects, compared with White subjects. Having only one parent employed was also independently associated with a very high EAT score, compared with having both parents employed. Similar associations were found for a moderately high EAT score (>10) and for a combination of low self-esteem and high EAT score. Low self-esteem and depressed mood were independently associated with a high EAT score. DISCUSSION: Ethnicity, socioeconomic position, self-esteem, and depression, but not gender, were independently associated with eating attitudes. Effects of cultural and socioeconomic stresses on eating disorders may be mediated through depressed mood and low self-esteem.

Gestão de custos para hospitais: conceitos, metodologias e aplicações / Management of costs to hospitals: concepts, methodologies and applications

Na visão da Associação Americana de Hospitais (AHA), já em 1980, os hospitais foram considerados como organizações particularmente complexas para a prestação de atividades altamente importantes na sociedade. Eles apresentavam níveis significativos de gastos e, frequentemente, foram os maiores empregadores dentro da comunidade onde estavam instalados. A previsão, naquele tempo, era de que a indústria de cuidados à saúde continuaria a crescer para ser uma das maiores indústrias da nação. Aparentemente, a previsão foi verificada não somente nos Estados Unidos, mas também em outros países. Todos os interessados, os governos federal, estadual e local, as financiadoras e mesmo alguns grupos de consumidores ficaram especialmente preocupados com o aumento crescente dos gastos dedicados à saúde e seu aparente baixo nível de eficácia. Como solução para esse escaloamento de custos, novos modelos de prestação de serviços foram sendo testados, no decorrer do tempo, numa tentativa de diminuir a demanda por serviços de saúde. Infelizmente, o termo custo tem acumulado diversos sentidos ou significados no decorrer do tempo. Essa ambiguidade exige que o gerente esteja consciente das diversas maneiras como o termo possa ser utilizado e onde seria relevante ser considerado na tomada de decisão