A non-linear discrete stochastic optimization model for Advanced Access patient appointment scheduling

Access to healthcare is a major problem in which patients are deprived of receiving timely admission to healthcare. Poor access has resulted in significant but avoidable healthcare cost, poor quality of healthcare, and deterioration in the general public health. Advanced Access is a simple and direct approach to appointment scheduling in which the majority of a clinic's appointments slots are kept open in order to provide access for immediate or same day healthcare needs and therefore, alleviate the problem of poor access the healthcare. This research formulates a non-linear discrete stochastic mathematical model of the Advanced Access appointment scheduling policy. The model objective is to maximize the expected profit of the clinic subject to constraints on minimum access to healthcare provided. Patient behavior is characterized with probabilities for no-show, balking, and related patient choices. Structural properties of the model are analyzed to determine whether Advanced Access patient scheduling is feasible. To solve the complex combinatorial optimization problem, a heuristic that combines greedy construction algorithm and neighborhood improvement search was developed. The model and the heuristic were used to evaluate the Advanced Access patient appointment policy compared to existing policies. Trade-off between profit and access to healthcare are established, and parameter analysis of input parameters was performed. The trade-off curve is a characteristic curve and was observed to be concave. This implies that there exists an access level at which at which the clinic can be operated at optimal profit that can be realized. The results also show that, in many scenarios by switching from existing scheduling policy to Advanced Access policy clinics can improve access without any decrease in profit. Further, the success of Advanced Access policy in providing improved access and/or profit depends on the expected value of demand, variation in demand, and the ratio of demand for same day and advanced appointments. The contributions of the dissertation are a model of Advanced Access patient scheduling, a heuristic to solve the model, and the use of the model to understand the scheduling policy trade-offs which healthcare clinic managers must make. ^

Social/economic costs and health-related quality of life in patients with epidermolysis bullosa in Europe

BACKGROUND: The aim of this study was to determine the social/economic costs and health-related quality of life (HRQOL) of patients with epidermolysis bullosa (EB) in eight EU member states. METHODS: We conducted a cross-sectional study of patients with EB from Bulgaria, France, Germany, Hungary, Italy, Spain, Sweden and the United Kingdom. Data on demographic characteristics, health resource utilisation, informal care, labour productivity losses, and HRQOL were collected from the questionnaires completed by patients or their caregivers. HRQOL was measured with the EuroQol 5-domain (EQ-5D) questionnaire. RESULTS: A total of 204 patients completed the questionnaire. Average annual costs varied from country to country, and ranged from euro9509 to euro49,233 (reference year 2012). Estimated direct healthcare costs ranged from euro419 to euro10,688; direct non-healthcare costs ranged from euro7449 to euro37,451 and labour productivity losses ranged from euro0 to euro7259. The average annual cost per patient across all countries was estimated at euro31,390, out of which euro5646 accounted for direct health costs (18.0 %), euro23,483 accounted for direct non-healthcare costs (74.8 %), and euro2261 accounted for indirect costs (7.2 %). Costs were shown to vary across patients with different disability but also between children and adults. The mean EQ-5D score for adult EB patients was estimated at between 0.49 and 0.71 and the mean EQ-5D visual analogue scale score was estimated at between 62 and 77. CONCLUSION: In addition to its negative impact on patient HRQOL, our study indicates the substantial social/economic burden of EB in Europe, attributable mostly to high direct non-healthcare costs.

The Genus Wolbachia

Numerous invertebrate species form long lasting symbioses with bacteria (Buchner, 1949; Buchner, 1965). One of the most common of these bacterial symbionts is Wolbachia pipientis, which has been estimated to infect anywhere from 15–75% of all insect species (Werren et al., 1995a; West et al., 1998; Jeyaprakash and Hoy, 2000; Werren and Windsor, 2000) as well as many species of arachnids, terrestrial crustaceans and filarial nematodes (O’Neill et al., 1997a; Bandi et al., 1998). In most arthropod associations, Wolbachia act as reproductive parasites manipulating the reproduction of their hosts to enhance their own vertical transmission. There appears to be little direct fitness cost to the infected host besides the costs arising from the reproductive manipulations. However instances have been reported where Wolbachia can be either deleterious (Min and Benzer, 1997; Bouchon et al., 1998) or beneficial (Girin and Boultreau, 1995; Stolk and Stouthamer, 1995; Wade and Chang, 1995; Vavre et al., 1999b; Dedeine et al., 2001) to their hosts. Wolbachia were first described as intracellular Rickettsia-like organisms (RLOs), infecting the gonad cells of the mosquito, Culex pipiens (Hertig and Wolbach, 1924), and were later named 'Wolbachia pipientis' (Hertig, 1936). It was not until the work of Yen and Barr (Yen and Barr, 1971; Yen and Barr, 1973) that Wolbachia were implicated in causing crossing incompatibilities between different mosquito populations (Laven, 1951; Ghelelovitch, 1952). When polymerase chain reaction (PCR) diagnostics for Wolbachia became available, it became clear that this agent was both extremely widespread and also responsible for a range of different reproductive phenotypes in the different hosts it infected (O’Neill et al., 1992; Rousset et al., 1992; Stouthamer et al., 1993). The most common of these are cytoplasmic incompatibility, inducing parthenogenesis, overriding host sex-determination, and male-killing (O’Neill et al., 1997a). As of the time of this writing, more than 450 different Wolbachia strains with unique gene sequences, different phenotypes, and infecting different hosts have been deposited in GenBank and the Wolbachia host database (http://www.wolbachia.sols. uq.edu.au).

Custos diretos do tratamento do cancro do cólon no Algarve

RESUMO - O cancro colorretal é um dos tumores mais comuns nos países desenvolvidos e um grave problema de saúde pública. Em Portugal constitui a terceira causa de morte por cancro em ambos os sexos e a segunda para cada sexo separadamente. A sua importância tem vindo a aumentar devido aos custos pessoais e sociais, surgindo internacionalmente como a segunda doença oncológica com os custos económicos mais elevados. No contexto atual, onde os gastos continuam a aumentar e os recursos são limitados, é importante tornar acessível aos decisores políticos o valor dos custos do cancro do cólon, para comparar opções para a prevenção e tratamento desta doença, no momento de afetar os recursos e financiamento do cancro. O objetivo do estudo é medir os custos diretos do tratamento do cancro do cólon na região do Algarve no ano de 2007. Para além da caracterização sociodemográfica e clínica dos doentes, pretende-se relacionar os custos das diferentes tipologias de diagnóstico e tratamento com os estádios da doença, com a idade e com o sexo. Propõe-se um estudo retrospetivo, analítico, transversal, que segue a abordagem custos da doença baseada na prevalência, adotando a perspetiva dos serviços de saúde. A principal fonte dos dados é a plataforma do ROR-Sul, extraindo-se a população constituída por todos os doentes com diagnóstico de cancro do cólon entre 1 de janeiro de 2007 e 31 de dezembro de 2007, residentes no distrito de Faro (n=170). Para a valorização dos custos recorre-se às Portarias que regulam as tabelas de preços dos serviços do Sistema Nacional de Saúde, à contabilidade analítica dos hospitais e ao Infarmed. Os resultados serão analisados através do Statistical Program for Social Sciences (SPSS) versão 20. De forma a verificar a existência de diferenças estatísticas, em termos de médias e da existência de relações, entre as variáveis sociodemográficas e clínicas utilizaram-se vários testes. Consideramos que este estudo será um importante ponto de partida para posteriores análises económicas completas, em termos dos seus custos e suas consequências, nomeadamente a realização da análise custo-efetividade de programas de prevenção primária e secundária do cancro do cólon.

Individualized Therapy with Ranibizumab in Wet Age-Related Macular Degeneration.

Individualized treatment regimens may reduce patient burden with satisfactory patient outcomes in neovascular age-related macular degeneration. Intravitreal anti-VEGF drugs are the current gold standard. Fixed monthly injections offer the best visual outcome but this regimen is not commonly followed outside clinical trials. A PRN regimen requires monthly visits where the patient is treated in the presence of signs of lesion activity. Therefore, an early detection of reactivation of the disease with immediate retreatment is crucial to prevent visual acuity loss. Several trials suggest that "treat and extend" and other proactive regimens provide a reasonable approach. The rationale of the proactive regimens is to perform treatment anticipating relapses or recurrences and therefore avoid drops in vision while individualizing patient followup. Treat and extend study results in significant direct medical cost savings from fewer treatments and office visits compared to monthly treatment. Current data suggest that, for one year, PRN is less expensive, but treat and extend regimen would likely be less expensive for subsequent years. Once a patient is not a candidate to continue with treatment, he/she should be sent to an outpatient unit with adequate resources to follow nAMD patients in order to reduce the burden of specialized ophthalmologist services.

Health care provider choice in the case of patient-initiated contacts. An extended version of discrete choice of model demand

This paper analyzes the nature of health care provider choice inthe case of patient-initiated contacts, with special reference toa National Health Service setting, where monetary prices are zeroand general practitioners act as gatekeepers to publicly financedspecialized care. We focus our attention on the factors that mayexplain the continuously increasing use of hospital emergencyvisits as opposed to other provider alternatives. An extendedversion of a discrete choice model of demand for patient-initiatedcontacts is presented, allowing for individual and town residencesize differences in perceived quality (preferences) betweenalternative providers and including travel and waiting time asnon-monetary costs. Results of a nested multinomial logit model ofprovider choice are presented. Individual choice betweenalternatives considers, in a repeated nested structure, self-care,primary care, hospital and clinic emergency services. Welfareimplications and income effects are analyzed by computingcompensating variations, and by simulating the effects of userfees by levels of income. Results indicate that compensatingvariation per visit is higher than the direct marginal cost ofemergency visits, and consequently, emergency visits do not appearas an inefficient alternative even for non-urgent conditions.

Failure of the surgical treatment in 115 infected hip arthroplasties-­analysis of a 12-­year prosthetic joint cohort study (1999-­2010)

Background:¦Infection after total or partial hip arthroplasty (HA) leads to significant long-­term morbidity and high healthcare cost. We evaluated reasons for treatment failure of different surgical modalities in a 12-­year prosthetic hip joint infection cohort study.¦Method:¦All patients hospitalized at our institution with infected HA were included either retrospectively (1999-­‐2007) or prospectively¦(2008-­‐2010). HA infection was defined as growth of the same microorganism in ≥2 tissues or synovialfluid culture, visible purulence, sinus tract or acute inflammation on tissue histopathology. Outcome analysis was performed at outpatient visits, followed by contacting patients, their relatives and/or treating physicians afterwards.¦Results:¦During the study period, 117 patients with infected HA were identified. We excluded 2 patients due to missing data. The average age was 69 years (range, 33-­‐102 years); 42% were female. HA was mainly performed for osteoarthritis (n=84), followed by trauma (n=22), necrosis (n=4), dysplasia(n=2), rheumatoid arthritis (n=1), osteosarcoma (n=1) and tuberculosis (n=1). 28 infections occurred early(≤3 months), 25 delayed (3-­‐24 months) and 63 late (≥24 months after surgery). Infected HA were¦treated with (i) two-­‐stage exchange in 59 patients (51%, cure rate: 93%), (ii) one-­‐stage exchange in 5 (4.3%, cure rate: 100%), (iii) debridement with change of mobile parts in 18 (17%, cure rate: 83%), (iv) debridement without change of mobile¦parts in 17 (14%, cure rate : 53% ), (v) Girdlestone in 13 (11%, cure rate: 100%), and (vi) two-­‐stage exchange followed by¦removal in 3 (2.6%). Patients were followed for an average of 3.9 years (range, 0.1 to 9 years), 7 patients died unrelated to the infected HA. 15 patients (13%) needed additional operations, 1 for mechanical reasons(dislocation of spacer) and 14 for persistent infection: 11 treated with debridement and retention (8 without change; and 3 with change of mobile parts) and 3 with two-­‐stage exchange. The average number of surgery was 2.2 (range, 1 to 5). The infection was finally eradicated in all patients, but the functional outcome remained unsatisfactory in 20% (persistent pain or impaired mobility due to spacer or Girdlestone situation).¦Conclusions:¦Non-­‐respect of current treatment concept leads to treatment failure with subsequent operations. Precise analysis of each treatment failure can be used for improving the treatment algorithm leading to better results.

Iowa Department of Public Health Affordable Care Act Impact Study, October 27, 2014

The mission of the Iowa Department of Public Health (IDPH) is “Promoting and Protecting the Health of Iowans.” In addition to its larger role in population health preparedness, surveillance, and response, IDPH has historically funded a broad array of health-related services to a “covered population” of approximately 1,000,000 Iowa residents through a varied network of local community-based “safety-net” provider contractors. Those health-related services range from funding direct healthcare services like immunizations and vision screening to providing or funding facilitative services like transportation and care coordination. While all Iowans may be eligible for some IDPH-funded direct healthcare service, such as smoking cessation, the individuals most often eligible for these services have traditionally been the uninsured and under-insured. As uninsured Iowans become enrolled in health plan options available through the Iowa Health and Wellness Plan (IHAWP) and the Marketplace, IDPH anticipates that many direct healthcare services funded by IDPH will become covered benefits or services under new plans, changing the demand for IDPH-funded services.

Estimation of lung cancer diagnosis and treatment costs based on a patient-level analysis in Catalonia (Spain)

Background: Assessing of the costs of treating disease is necessary to demonstrate cost-effectiveness and to estimate the budget impact of new interventions and therapeutic innovations. However, there are few comprehensive studies on resource use and costs associated with lung cancer patients in clinical practice in Spain or internationally. The aim of this paper was to assess the hospital cost associated with lung cancer diagnosis and treatment by histology, type of cost and stage at diagnosis in the Spanish National Health Service. Methods: A retrospective, descriptive analysis on resource use and a direct medical cost analysis were performed. Resource utilisation data were collected by means of patient files from nine teaching hospitals. From a hospital budget impact perspective, the aggregate and mean costs per patient were calculated over the first three years following diagnosis or up to death. Both aggregate and mean costs per patient were analysed by histology, stage at diagnosis and cost type. Results: A total of 232 cases of lung cancer were analysed, of which 74.1% corresponded to non-small cell lung cancer (NSCLC) and 11.2% to small cell lung cancer (SCLC); 14.7% had no cytohistologic confirmation. The mean cost per patient in NSCLC ranged from 13,218 Euros in Stage III to 16,120 Euros in Stage II. The main cost components were chemotherapy (29.5%) and surgery (22.8%). Advanced disease stages were associated with a decrease in the relative weight of surgical and inpatient care costs but an increase in chemotherapy costs. In SCLC patients, the mean cost per patient was 15,418 Euros for limited disease and 12,482 Euros for extensive disease. The main cost components were chemotherapy (36.1%) and other inpatient costs (28.7%). In both groups, the Kruskall-Wallis test did not show statistically significant differences in mean cost per patient between stages. Conclusions: This study provides the costs of lung cancer treatment based on patient file reviews, with chemotherapy and surgery accounting for the major components of costs. This cost analysis is a baseline study that will provide a useful source of information for future studies on cost-effectiveness and on the budget impact of different therapeutic innovations in Spain.

Viestintä ravitsemusosaamisen kehittämisessä Case:Sairaalan ateriaprosessi

Tutkielman tarkoituksena oli tutkia viestinnän merkitystä osaamisen kehittämisessä. Tavoitteena oli tutkia, miten viestintä edistää ravitsemusosaamisen kehittämistä sairaalan ateriaprosessissa. Tutkimuksessa etsittiin vastausta kysymyksiin, mitkä ovat ravitsemusosaamisen kehittämisen ja viestinnän tavoitteet, millä työyhteisöviestinnän foorumeilla uuden ravitsemushoitosuosituksen ja ravitsemushoidon strategian edellyttämiä muutoksia käsitellään ja millaisia työssä oppimisen prosesseja näillä foorumeilla on tunnistettavissa. Empirian näkökulmasta tutkimusta voidaan kuvata tapaustutkimukseksi. Tapauksena on sairaalan ateriaprosessi. Tutkimuksen valmistelevana aineistona käytettiin uutta ravitsemushoitosuositusta (Nuutinen ym. 2010), jota täydennettiin haastatteluaineistolla. Tutkimuksessa ovat edustettuina hoitotyön, ruokapalvelun ja ravitsemushoidon asiantuntemuksen näkökulmat sairaalasta sekä ammatti- ja aikuisopistosta. Tutkimusmenetelmänä käytettiin teemahaastatteluja. Haastattelut nauhoitettiin ja litteroitiin tekstimuotoon. Aineisto analysoitiin teemakortiston ja teemoittelun avulla. Tutkimuksen tulokset osoittavat, että ravitsemusosaamisen kehittämisen tavoitteena on uuden ravitsemushoitosuosituksen ja ravitsemushoidon strategian edellyttämien muutosten toteuttaminen sairaalan ravitsemushoidon prosesseissa ja tuotteissa. Ravitsemusosaamisen kehittämisen tavoitteena on tässä yhteydessä ateriaprosessin ja ruokapalvelun tuotteiden eli ruokavalioiden kehittäminen. Ravitsemushoidon kehittämisen tarkoituksena on asiakkaiden toipumisen, elämänlaadun ja hyvinvoinnin edistäminen sekä terveydenhuollon kustannusten säästäminen. Viestinnällä on tärkeä merkitys ravitsemusosaamisen kehittämisessä. Viestinnän avulla edistetään yksilöllistä ja yhteistä eli tiimioppimista vuorovaikutuksen kautta. Ruokapalvelu- ja hoitohenkilöstön sekä ravitsemushoidon asiantuntijoiden välinen vuoropuhelu nähdään tärkeänä ravitsemusosaamisen kehittämisessä. Vuoropuhelun avulla vahvistetaan ravitsemushoitoon liittyvää tietopohjaa ja yhteistä käsitteistöä. Tavoitteena on yhteisen kielen ja toimintamallin luominen ravitsemushoidon kehittämiseen. Ravitsemushoitosuosituksen ja ravitsemushoidon strategian edellyttämiä muutoksia käsitellään ulkoisissa ja sisäisissä verkostoissa esimerkiksi ravitsemus-yhdyshenkilöverkoston tapaamisissa, moniammatillisissa työryhmissä, henkilöstö- ja oppisopimuskoulutuksissa sekä työfoorumilla eli fyysisessä työtilassa ja hyödyntäen viestintäteknologiaa. Hoitotyön, ruokapalvelun ja ravitsemushoidon asiantuntijoilla/opettajilla on tärkeä rooli ravitsemusosaamisen kehittämiseen liittyvässä työssä oppimisen ohjaamisessa. Ravitsemusosaamisen kehittämisessä on tunnistettavissa sosiaalisia, reflektiivisiä, kognitiivisia ja operationaalisia työssä oppimisen prosesseja. Sosiaalisia prosesseja ovat työkokemusten vaihdanta ja reflektiivisiä niiden arviointi. Kognitiivisten prosessien tarkoitus on tiedonhankinta ja prosessointi, jolloin yhdistetään kokemustietoa sekä uutta ravitsemustieteellistä tietoa. Tavoitteena on yhteisen kielen ja toimintamallin luominen, jota kokeillaan käytännössä. Operationaalisia prosesseja ovat fyysisessä työtilassa tapahtuva kokeilemalla, tekemällä ja soveltamalla oppiminen, jolloin uutta toimintamallia esimerkiksi vajaaravitsemuksen seulontaa, ateriatilausta tai reseptiikkaa kokeillaan käytännössä. Johtopäätöksenä voidaan todeta, että sairaalassa on omaksuttu oppivan organisaation periaatteita ravitsemusosaamisen kehittämisessä. Ravitsemusosaamisen kehittäminen on yhteydessä muutokseen, strategiaan, prosessien ja tuotteiden kehittämiseen. Viestinnän avulla edistetään ravitsemushoitosuosituksen ja ravitsemushoidon strategian edellyttämien muutosten toteuttamista sairaalan ateriaprosessissa ja ruokavalioissa. Hoito- ja ruokapalveluhenkilöstön sekä ravitsemushoidon asiantuntijoiden välisen vuoropuhelun tavoitteena on yhteisen kielen ja toimintamallin luominen ravitsemushoidon kehittämiseen. Tutkimus palvelee ravitsemusosaamisen kehittämistä sairaalan ateriaprosessissa. Tutkimuksen tuloksia on mahdollista käyttää vertailuoppimismateriaalina terveydenhuollon organisaatioissa ja verkostoissa.

Les coûts des soins de santé chez les personnes âgées de 65 ans et plus avec incapacités au Québec

La question des coûts des soins de santé gagne en intérêt dans le contexte du vieillissement de la population. On sait que les personnes en moins bonne santé, bien que vivant moins longtemps, sont associées à des coûts plus élevés. On s'intéresse aux facteurs associés à des coûts publics des soins de santé plus élevés au niveau individuel, chez les Québécois vivant en ménage privé âgés de 65 ans et plus, présentant au moins un type d’incapacité. À l’aide de modèles de régression, la variation des coûts pour la consultation de professionnels de la santé et la prise de médicaments a été analysée en fonction du nombre d’incapacités ainsi que de la nature de celles-ci. Les informations sur l’état de santé et la situation socio-démographique proviennent de l’Enquête sur les limitations d’activités (EQLA) de 1998, celles sur les coûts du Fichier d’inscription des personnes assurées (FIPA) de la Régie de l’Assurance maladie du Québec (RAMQ), pour la même année. Les résultats montrent que les deux types de coûts considérés augmentent en fonction du nombre d’incapacités. D’autre part, des coûts plus élevés ont été trouvés chez les personnes présentant une incapacité liée à l’agilité concernant la consultation de professionnels de la santé, alors que, concernant la prise de médicaments, le même constat s’applique aux personnes avec une incapacité liée à la mobilité. Les deux types de coûts considérés présentent un niveau plus élevé chez les personnes présentant une incapacité liée au psychisme, en particulier lorsque l’on considère la prise de médicaments. Ces observations soulignent l’intérêt de considérer la nature du problème de santé lorsque l’on étudie les déterminants individuels du niveau des coûts des soins de santé.

Small-area variation in health care affecting the choice of cesarean delivery: the case of a Colombian health insurer

In the midst of health care reform, Colombia has succeeded in increasing health insurance coverage and the quality of health care. In spite of this, efficiency continues to be a matter of concern, and small-area variations in health care are one of the plausible causes of such inefficiencies. In order to understand this issue, we use individual data of all births from a Contributory-Regimen insurer in Colombia. We perform two different specifications of a multilevel logistic regression model. Our results reveal that hospitals account for 20% of variation on the probability of performing cesarean sections. Geographic area only explains 1/3 of the variance attributable to the hospital. Furthermore, some variables from both demand and supply sides are found to be also relevant on the probability of undergoing cesarean sections. This paper contributes to previous research by using a hierarchical model and by defining hospitals as cluster. Moreover, we also include clinical and supply induced demand variables.

Dropout: MOOC participants’perspective

Massive Open Online Courses (MOOCs) open up learning opportunities to a large number of people. A small percentage (around 10%) of the large numbers of participants enrolling in MOOCs manage to finish the course by completing all parts. The term ‘dropout’ is commonly used to refer to ‘all who failed to complete’ a course, and is used in relation to MOOCs. Due to the nature of MOOCs, with students not paying enrolment and tuition fees, there is no direct financial cost incurred by a student. Therefore it is debatable whether the traditional definition of dropout in higher education could be directly applied to MOOCs. This paper reports ongoing exploratory work on MOOC participants’ perspectives based on six qualitative interviews. The findings show that MOOC participants are challenging the widely held view of dropout, suggesting that it is more about failing to achieve their personal aims.

Rede e apoio social entre idosos atendidos em um ambulatório de Geriatria

O objetivo geral deste estudo foi analisar a relação entre a rede e apoio social, satisfação com o apoio social recebido e as variáveis sociodemográficas, de saúde física e mental, dos idosos atendidos em um Ambulatório de Geriatria de um Hospital Geral Terciário do interior paulista. Trata-se de um estudo descritivo, transversal e exploratório, realizado com 98 idosos atendidos no referido ambulatório. Para a coleta de dados, utilizaram-se o Mini Exame do Estado Mental, um questionário de caracterização sociodemográfica e de saúde, a Escala de Depressão Geriátrica (EDG-15), o Índice de Katz, a Escala de Lawton e Brody, a Escala de medida da rede e apoio social do Medical Outcomes Study e a Escala de Satisfação com o Suporte Social. Os aspectos éticos foram respeitados conforme a Resolução 466/2012 do Conselho Nacional de Saúde. A média de idade dos idosos foi de 80,1 anos, 70,4% eram mulheres, 49,0% viúvos; a média de anos de estudo foi 2,3; 24,5% dos idosos residiam com o cônjuge e filhos ou somente com os filhos; a renda familiar média foi de R$1.773,70. Quanto à capacidade funcional, 80,6% eram independentes para as atividades básicas da vida diária e 88,8% eram parcialmente dependentes para as instrumentais. Os idosos possuíam, em média, 5,3 diagnósticos médicos e os sintomas depressivos estiveram presentes para 61,2% deles. Quanto à rede social, o escore total médio foi de 6,4 pessoas para contato na rede, sendo que 36,7% apresentavam médio contato e participação em atividades sociais. Em relação ao apoio social, o maior escore médio foi para a dimensão material (90,2) e o menor para a interação social positiva (81,8); já para a satisfação com o suporte social, 36,7% e 32,7% apresentaram alta e média satisfação, respectivamente. Foi encontrada correlação inversa entre os escores de todas as dimensões da escala de apoio social e os escores da EDG-15, indicando que quanto maior o apoio social em todas as dimensões, menor é a presença de sintomas depressivos e houve diferenças estatisticamente significativas para todas as dimensões, material (p=0,014), afetiva (p=0,026), interação (p=0,011), emocional (p=0,001) e informação (p=0,005); já a correlação entre os escores das dimensões da escala de apoio social e os escores na escala de Lawton e Brody, foi inversa e fraca para as dimensões material (r=-0,157) e informação (r=-0,027), sugerindo que quanto menor a independência para as AIVDs, maior o apoio social nas referidas dimensões, porém, não houve diferença estatisticamente significativa, material (p=0,121) e informação (p=0,789). A correlação entre os escores da EDG-15 e os escores da escala de satisfação com o apoio social, foi inversa e moderada (r=- 0,467), indicando que quanto maior a satisfação com o apoio social, menor a presença de sintomas depressivos, sendo estatisticamente significativa (p=0,000). Evidencia-se a importância de conhecer se os idosos estão inseridos em rede social e se percebem o apoio social para um melhor direcionamento da assistência prestada ao idoso e para o planejamento e formulação de políticas públicas, programas e projetos voltados a essa população

Regulation of Rab5 GTPase activity during Pseudomonas aeruginosa-macrophage interaction

Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen. Several antibiotic resistant strains of P. aeruginosa are commonly found as secondary infection in immune-compromised patients leaving significant mortality and healthcare cost. Pseudomonas aeruginosa successfully avoids the process of phagocytosis, the first line of host defense, by secreting several toxic effectors. Effectors produced from P. aeruginosa Type III secretion system are critical molecules required to disrupt mammalian cell signaling and holds particular interest to the scientists studying host-pathogen interaction. Exoenzyme S (ExoS) is a bi-functional Type III effector that ADP-ribosylates several intracellular Ras (Rat sarcoma) and Rab (Response to abscisic acid) small GTPases in targeted host cells. The Rab5 protein acts as a rate limiting protein during phagocytosis by switching from a GDP- bound inactive form to a GTP-bound active form. Activation and inactivation of Rab5 protein is regulated by several Rab5-GAPs (GTPase Activating Proteins) and Rab5-GEFs (Rab5-Guanine nucleotide Exchange Factors). Some pathogenic bacteria have shown affinity for Rab proteins during infection and make their way inside the cell. This dissertation demonstrated that Rab5 plays a critical role during early steps of P. aeruginosa invasion in J774-Eclone macrophages. It was found that live, but not heat inactivated, P. aeruginosa inhibited phagocytosis that occurred in conjunction with down-regulation of Rab5 activity. Inactivation of Rab5 was dependent on ExoS ADP-ribosyltransferase activity, and more than one arginine sites in Rab5 are possible targets for ADP-ribosylation modification. However, the expression of Rin1, but not other Rab5GEFs (Rabex-5 and Rap6) reversed this down-regulation of Rab5 in vivo. Further studies revealed that the C-terminus of Rin1 carrying Rin1:Vps9 and Rin1:RA domains are required for optimal Rab5 activation in conjunction with active Ras. These observations demonstrate a novel mechanism of Rab5 targeting to phagosome via Rin1 during the phagocytosis of P. aeruginosa. The second part of this dissertation investigated antimicrobial activities of Dehydroleucodine (DhL), a secondary metabolite from Artemisia douglasiana, against P. aeruginosa growth and virulence. Populations of several P. aeruginosa strains were completely susceptible to DhL at a concentration between 0.48~0.96 mg/ml and treatment at a threshold concentration (0.12 mg/ml) inhibited growth and many virulent activities without damaging the integrity of the cell suggesting anti-Pseudomonas activity of DhL.