There is increasing interest in the use of adjuvant hormonal therapies, which are given after the resection or destruction of all gross disease, in early-stage prostate cancer, as a significant proportion of patients experience progression and/or die from the disease despite undergoing therapy with curative intent. Several retrospective studies suggest that adjuvant hormonal therapy may improve long-term outcome after radical surgery in men with positive lymph nodes, although this approach has yet to be studied in a prospective setting. No studies of adjuvant therapy for patients with extracapsular extension at surgery have been completed, but in an interim analysis of an open controlled trial, adjuvant flutamide significantly improved progression-free survival at 4 years. Three prospective studies in the radiotherapy setting have shown that adjuvant luteinizing hormone-releasing hormone (LH-RH) agonist therapy significantly improves progression-free and/or overall survival. Future studies need to define patient subgroups who will benefit most from adjuvant therapy. The side effects of the different therapeutic options also need to be compared. It is hoped that many of the outstanding questions concerning adjuvant hormonal therapy will be answered by the ongoing Bicalutamide Early Prostate Cancer Programme. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

As neoplasias mamárias em cadelas são afecções de significativa importância em medicina veterinária pela sua alta frequência, além de serem modelo para o estudo do câncer de mama na mulher. Nesse sentido, se faz necessária a realização de estudos continuados acerca da frequência de tumores e suas características clinicopatológicas. Constituem ainda um grupo heterogêneo de tumores quanto aos padrões histológicos e comportamento biológico, o que torna mais complexo e urgente a identificação de fatores de prognóstico e que possibilitem diagnosticar e tratar de forma mais eficaz animais portadores de tumor de mama. Nos últimos anos, tem se intensificado estudos dirigidos à identificação de marcadores moleculares envolvidos nos inúmeros eventos celulares que ocorrem durante a carcinogênese, como crescimento e diferenciação celular, proliferação, invasão e metástase. O receptor do fator de crescimento epidérmico humano tipo 2 (HER-2) é uma glicoproteína de membrana da família tirosina-quinase, codificada por um gene de mesmo nome, diretamente relacionada a mudanças significativas na proliferação celular e sobrevivência das células tumorais. Durante o processo de mutação desse gene ocorre hiperativação da cascata de sinalização intracelular, que resulta em rápido crescimento das células tumorais. Na mulher, a superexpressão de HER-2 está associada a neoplasias mamárias cujos parâmetros morfológicos sugerem malignidade e pior prognóstico, resultando em alta taxa de recidiva e de mortalidade no estágio inicial da doença, além de elevada incidência de metástases. Entretanto, na cadela, estudos que investigaram o papel do HER-2 nas neoplasias mamárias, com emprego da imunohistoquímica, não são consensuais até então, mantendo obscuro o significado da sobrexpressão de HER-2 nestas neoplasias. Com intuito de auxiliar na determinação de fatores prognósticos fidedignos para os tumores mamários nas cadelas, o presente trabalho teve como objetivos: determinar a prevalência de lesões mamárias diagnosticadas em cadelas no Laboratório de Patologia Veterinária da Universidade Federal de Uberlândia entre 2004 e 2014, bem como a relação entre aspectos epidemiológicos (idade e raça) e clínicopatológicos (ulceração, tamanho do tumor e comportamento biológico) na ocorrência dos tumores de mama; e verificar a expressão de HER-2 em carcinomas mamários de cadelas e sua relação com o tipo e grau histológico, idade das cadelas, metástase em linfonodos e à distância, tamanho tumoral e estadiamento clínico. / Mammary tumors in female dogs are important diseases in veterinary medicine due to their high frequency, besides being a model for the study of breast cancer in women. So, it is necessary to continuous studies on the frequency of tumors and their clinicopathological characteristics. They also constitute a heterogeneous group of tumors in correlation with histological patterns and biological behavior, which makes it more complex and urgent to identify prognostic factors and to make it possible to diagnose and treat animals with mammary tumors more effectively. In the last years, there have been intensified the number of studies about the identification of molecular markers involved in the innumerable cellular events that occur during carcinogenesis, such as cell growth and differentiation, proliferation, invasion and metastasis. HER-2 is a membrane glycoprotein of the tyrosine kinase family, encoded by a gene with the same name, directly related to significant changes in cell proliferation and survival of tumor cells. During mutation process of this gene, hyperactivation of intracellular signaling cascade results in a rapid growth of tumor cells. In women, HER-2 overexpression is associated with breast neoplasms whose morphological parameters suggest poor prognosis and malignancy, resulting in a high rate of recurrence and mortality in the early stage of the disease, as well as a high incidence of metastases. However, in the female dog, until now the extensive variability of results obtained from immunohistochemical protocols proposed for molecular classification, keeps the meaning of HER-2 overexpression in these neoplasms obscure. In order to assist determination of the reliable prognostic factors for canine breast neoplasms, the present study: determined the prevalence of breast lesions diagnosed in female dogs in Laboratory of Veterinary Pathology of the Federal University of Uberlândia between 2004 and 2014, as well as the correlation between epidemiological aspects (age and breed) and clinicopathological (ulceration, tumor size and biological behavior) in the occurrence of breast tumors; verified the HER-2 expression in female mammary carcinomas of dogs and their relationship with the type and histological grade, age of patient, metastasis in lymph nodes or distants, tumor size and clinical staging. / Tese (Doutorado)

Submitted by Geandra Rodrigues (geandrar@gmail.com) on 2018-09-04T15:39:47Z No. of bitstreams: 1 homerogoncalvesjunior.pdf: 2526505 bytes, checksum: e3bc0f5bc2176febea8072cc318baab6 (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2018-09-04T15:52:35Z (GMT) No. of bitstreams: 1 homerogoncalvesjunior.pdf: 2526505 bytes, checksum: e3bc0f5bc2176febea8072cc318baab6 (MD5) / Made available in DSpace on 2018-09-04T15:52:35Z (GMT). No. of bitstreams: 1 homerogoncalvesjunior.pdf: 2526505 bytes, checksum: e3bc0f5bc2176febea8072cc318baab6 (MD5) Previous issue date: 2018-07-06 / O tratamento do câncer de mama baseia-se na classificação dos casos, em termos de estadiamento e do perfil biomolecular. Os Tumores Triplo Negativos (TTN) representam um grupo especial de neoplasias mamárias que não expressam receptores hormonais e nem o antígeno Her2. São considerados agressivos e de pior evolução, e quando estudados em particular, apresentam muita heterogeneidade. Importa saber se a caracterização dos tumores como Triplo Negativos, é suficiente para delimitar o grupo em termos de prognóstico e terapêutica. Este estudo teve como objetivo comparar os aspectos clínico-epidemiológicos dos Tumores Triplo Negativos em relação aos Não Triplo Negativos, em coorte de mulheres com câncer de mama assistidas em centros oncológicos de referência de Juiz de Fora, Minas Gerais. A sobrevida global e a sobrevida livre de doença foram calculadas pelo método de Kaplan Meier, e as curvas de sobrevida foram avaliadas pelo teste de Log-Rank, nos subgrupos Triplo Negativos e Não Triplo Negativos (NTN). Os fatores prognósticos foram comparados pelo modelo de riscos proporcionais de Cox. Os Tumores Triplo Negativos apresentaram diferenças demográficas em relação aos NTN, com acúmulo de pacientes não brancas e de baixo nível sociocultural; e ainda com aspectos de maior gravidade ao diagnóstico. A evolução também foi pior, tanto em termos de sobrevida global quanto sobrevida livre de doença dentre os TTN. Na análise univariada, os fatores: idade, cor da pele, escolaridade, tamanho do tumor e grau tumoral, estado das axilas e estadiamento, bem como taxas elevadas dos marcadores P53 e Ki 67, se mostraram associados a sobrevida livre de doença nos Tumores Não Triplo Negativos. No cálculo da sobrevida global, essas variáveis se mantiveram, exceto a idade; e foi constatado maior risco para as mulheres oriundas do serviço público de saúde, bem como o surgimento de metástases no decurso do seguimento. Para os Triplo Negativos, a análise univariada mostrou influência do estado axilar e estadiamento na sobrevida livre de doença; e os mesmos fatores acrescidos do surgimento de metástases, para a sobrevida global. Na análise multivariada a escolaridade e o estado axilar representaram risco à sobrevida livre de doença para NTN, enquanto a cor da pele e o estadiamento para a sobrevida global. Quanto aos TTN, sua evolução se mostrou ligada a dois aspectos: o comprometimento axilar para sobrevida livre de doença e global; e também a multicentricidade para a sobrevida global. Os Tumores Triplo Negativos aparentam ter biologia bem diversa dos Não Triplo Negativos, na dependência dos componentes histológicos e moleculares que portam. A classificação molecular por imunoistoquímica se mostrou capaz de identificar os dois grupos tumorais e auxiliar na orientação terapêutica. / Current breast cancer treatment is based on the classification of tumor stage and molecular profile. Triple-negative breast cancer (TNBC) is a specific subset of tumors characterized by the absence of hormone and HER2 receptors. Despite being usually associated with a more aggressive clinical course, there is high heterogeneity within TNBC. Therefore, it has been questioned whether current classification of TNBC is adequate enough to assess its prognosis and make therapeutic decisions. This study thus aimed to investigate to which extent TNBC profile classification was able to efficiently distinguish this tumor subtype from other subtypes of breast cancer. It was performed on a cohort of women with breast cancer treated at referral centers in Juiz de Fora, Southeastern Brazil. Overall and disease-free survival and prognostic factors were assessed and compared for TNBC and non-TNBC. Survival functions were calculated using the Kaplan-Meier method, and the log-rank test was used to compare the survival curves. Prognostic factors were analyzed by the Cox proportional hazards model. TNBC presented demographic differences compared to non-TNBC as it was more prevalent among nonwhite and less educated women. TNBC also presented at diagnosis with clinical parameters of advanced disease and had overall and disease-free survival significantly lower than non-TNBC. In univariate analysis the factors: age, color of the skin, education level, size and degree of tumor, axillary status and staging, as well as high rates of P53 e Ki 67 have been shown to be associated with disease-free survival in non-TNBC. These variables remained the same in the calculation of overall survival except for age; and it was also observed a greater risk for women from the public health service as well as the appearance of metastases during the follow-up. In multivariate analysis education level and axillary lymph node involvement presented a risk for disease-free survival while the color of skin and staging, for overall survival in non-TNBC. Regarding TNBC, its evolution was related to two aspects: axillary impairment for disease-free and global survival and multicentricity for overall survival. TNBC presents distinct biological properties compared to non-TNBC, which seems to be related to its specific histological and molecular components. The molecular classification by immunohistochemistry showed to be able to identify the two tumor groups and to support the therapeutic orientation.

Submitted by Ubirajara Cruz (ubirajara.cruz@gmail.com) on 2016-09-21T16:39:07Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) dissertacao_daniela_silva.pdf: 1064609 bytes, checksum: 8a6b89b15f9df72c182d7fe50c38554f (MD5) / Approved for entry into archive by Aline Batista (alinehb.ufpel@gmail.com) on 2016-09-21T16:49:28Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) dissertacao_daniela_silva.pdf: 1064609 bytes, checksum: 8a6b89b15f9df72c182d7fe50c38554f (MD5) / Made available in DSpace on 2016-09-21T16:49:28Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) dissertacao_daniela_silva.pdf: 1064609 bytes, checksum: 8a6b89b15f9df72c182d7fe50c38554f (MD5) Previous issue date: 2014-02-28 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / O presente trabalho é constituído por estudos que visam avaliar potenciais marcadores prognósticos para tumores mamários caninos. Realizou-se um levantamento retrospectivo dos dados do Laboratório Regional de Diagnóstico da Faculdade de Veterinária da Universidade Federal de Pelotas (UFPel) acerca da casuística de dados clínico-patológicos de paciente com tumores mamários em diferentes períodos entre 2000-2012. A dissertação está apresentada na forma de dois artigos científicos. O primeiro artigo consiste da avalição do valor prognóstico do método de graduação de Elston e Ellis (1991). Foram avaliados 218 tumores. Verificou-se que a relação entre o tipo de tumor e tempo de sobrevida dos pacientes foi significativo (p<0,0001); que a maioria dos tumores pertenciam ao grau II (77/144-53.52%) e o grau tumoral influencia no tempo de sobrevida (p<0,0447). No segundo artigo estudou-se a possibilidade do uso da mensuração da densidade microvascular como fator prognóstico em tumores mamários caninos. Inicialmente dois métodos diferentes de mensuração de densidade vascular (campos aleatórios e hot-spot) foram avaliados e demonstrou-se que são equivalentes. Verificou-se que tanto a contagem de campos aleatórios ou contagem em áreas de intensa proliferação vascular apresentam resultados similares. Nos 218 neoplasmas avaliados não houve relação significativa entre o tipo histológico e o grau em relação a mensuração densidade microvascular, avaliadas pelos 2 métodos. Tumores de grau I apresentaram mais vasos que os de grau II e III. Conclui-se que no presente trabalho os carcinossarcomas foram os tumores mais prevalentes na casuística avaliada; que a associação do tipo e grau histológico tem valor prognóstico, enquanto que densidade microvascular não é um bom fator prognóstico para tumores mamários caninos. / This manuscript aims evaluate potential morphological prognostic factors to canine mammary tumors. Retrospective chart reviews of data from the Regional Diagnostic Laboratory were carried out to obtain the clinical and pathological features of the patients and mammary tumors in different periods from 2000 to 2012. The dissertation will be presented as two scientific manuscripts. The first manuscript aims the evaluation of the prognostic graduation method of Elston e Ellis (1991). A total of 218 tumors were evaluated. The relationship between tumor type and survival time were significant (p<0.0001). It was observed a preponderance of grade II (77/144-53.52%) tumors and also that the tumor grade can influence survival time (p<0.0447). The second manuscript evaluates the microvascular density as a prognostic factor in canine mammary tumors. Initially, two methods of mensuration (aleatory fields and hot spot) were evaluated and proved to be equivalent. In the 218 tumors evaluated no significant results were obtained in the comparison of histologic type or tumor grade with microvascular density evaluated by both methods. Grade I tumors presented more vessels than grade II or III tumors. It was possible to conclude that carcinosarcomas are the prevalent tumor type; association between tumor type and histologic grade could be used as prognostic factor. Microvascular density not consists in a good prognostic factor.

Submitted in partial compliance with the requirements for the Master’s Degree in Technology: Chiropractic, Durban University of Technology, Durban, South Africa, 2017. / Background: The increasing cost and prevalence of chronic low back pain (LBP), has resulted in more resources being devoted to its treatment and management than ever before, despite only approximately 10% of acute cases progressing to chronicity. Determining prognostic factors for the short-term improvement of acute and chronic patients with LBP has become a research focus area to try and identify baseline factors that may affect a patients’ improvement with conservative treatment. Internationally studies have been conducted in developed countries however similar studies are lacking in developing settings like South Africa. It is unclear if the prognostic factors identified would be similar across populations. Thus, this study aimed to determine if pain, disability (social and physical), anxiety, depression, work fear-avoidance and locus of control, were associated with short-term prognosis, as determined by self-reported improvement using a Patients Global Impression of Change (PGIC) scale, in acute and chronic LBP patients attending the Durban University of Technology Chiropractic Day Clinic (DUT CDC). Method: Consecutive patients seeking treatment at the DUT CDC with a new episode of non-specific LBP, who met the study criteria, were approached for participation in the study. On agreeing to participate they were given the Bournemouth Questionnaire (BQ), a demographic questionnaire and a letter of information and consent (LOIC) at the initial consultation by student chiropractors. Those participants that were still attending treatment at the 4th/5th and tenth visit were required to complete the BQ and the PGIC. Results: A hundred participants were enrolled in the study, 65% had acute LBP and 52% were male. Only 20% of the initial group were still attending treatment at the 4th/5th follow-up. Baseline comparisons of those with acute and chronic pain revealed no significant difference in gender or age. Acute patients at the initial visit had higher levels of disability (social and physical), anxiety, depression and fear-avoidance beliefs than the chronic pain participants. At the 4th/5th treatment, the acute pain patients showed a significant decrease in pain (p=0.002) and disability (p=0.032), with all other measures decreasing from baseline measures. Similarly, chronic pain participants had a significant decrease in pain (p=0.038) but a significant increase in depression (p=0.015) scores, with all other prognostic factors being rated higher than at the initial consultation. The majority of participants (85%) in this study reported a clinical improvement in their LBP. In the acute pain sufferers, all but one participant reported improvement, thus identification of prognostic factors or this group was not possible. In the chronic pain participants, no factors were identified as prognostic for improvement, regardless of the low numbers still attending at the 4th/5th visit. Conclusions: Trends suggested that chronic pain sufferers were less likely to report decreases in the prognostic factors (except for pain), when compared to the acute pain participants. In the chronic LBP participants, no factors were associated with improved prognosis. The predictive value in determining which patients were less likely to improve was limited in the current study due to a small sample size. / M

Purpose: To evaluate the validity of the Gleason score after neoadjuvant hormonal treatment as predictor of diseasespecific mortality after radical prostatectomy. Patients and Methods: A total of 2,880 patients with a complete data set and a mean follow-up of 10.3 years were studied; 425 of them (15%) had a history of hormonal treatment prior to surgery. The cumulative incidence of deaths from prostate cancer was determined by univariate and multivariate competing risk analysis. Cox proportional hazard models for competing risks were used to study combined effects of the variables on prostate cancer-specific mortality. Results: A higher portion of specimens with a history of neoadjuvant hormonal treatment were assigned Gleason scores of 8–10 (28 vs. 17%, p < 0.0001). The mortality curves in the Gleason score strata <8 vs. 8–10 were at large congruent in patients with and without neoadjuvant hormonal treatment. In patients with neoadjuvant hormonal treatment, a Gleason score of 8–10 was an independent predictor of prostate cancer-specific mortality; the hazard ratio was, however, somewhat lower than in patients without neoadjuvant hormonal treatment. Conclusion: This study suggests that the prognostic value of the post-radical prostatectomy Gleason score is not meaningfully jeopardized by heterogeneous neoadjuvant hormonal treatment in a routine clinical setting.

Patients and methods: Malignant supratentorial glioma (anaplastic astrocytoma, oligoastrocytoma, oligodendroglioma and glioblastoma incl. gliosarcoma), age 16-70y, KPS 50-100. Postoperative randomization to chemotherapy with either BCNU (B) (80 mg/m2 x 3 every 6 weeks) alone or additional VM 26 (V) (50 mg/m2 x 3 every 6 weeks) starting concomitant with radiotherapy. Central histopathological review was required. Primary endpoints were survival time (ST) and progression free survival (PFS) . In addition confirmative analysis of prognostic factors and their interaction with therapy was performed. Results: Eligible: 501 of 522 randomized pts: 82% WHO grade IV gliomas, 18% grade III gliomas. 57% male, mean KPS 74, mean age 50.9 years. The high incidence of lung toxicity – with a cumulative risk of 19% during the first year - was alarming. Survival was not significantly different ( median 50.3 (B) versus 52.4 (V) (weeks), but an increase in long term survivors was observed (18 months: 29% B, 34% V, 5 years 5% B, 12% V) and PFS showed a significant difference with a median of 31.4 (B) versus 34.3 (V) weeks. Qualitative interaction between KPS and therapy (p < 0.01) was demonstrated: pts with a KPS ≥ 70 benefited from additional VM26, those with reduced KPS < 70 did better with BCNU-monotherapy. Conclusion: Adding VM26 to BCNU is effective in the chemotherapy of malignant gliomas. Because of the demonstrated interaction with therapy performance status, not tumor grade is the crucial factor to determine application and aggressiveness of chemotherapy. With risk adapted therapy a significant proportion of patients even with glioblastoma survive for years in good general condition. BCNU should be replaced by an equipotent alkylans to avoid the unacceptable high rate of lung toxicity.

Background: Factors predicting survival in men with lymph node-positive prostate cancer are still poorly defined. Patients and Methods: 193 prostate cancer patients with histopathologically proven lymph node involvement with a median follow-up of 7.3 years were studied. 94% of patients received immediate hormonal therapy. Kaplan-Meier curves were calculated to evaluate overall survival rates and compared with the log-rank test. Cumulative disease-specific and competing mortality rates were calculated by competing risk analysis and compared with the Pepe-Mori test. Cox proportional hazard models were used to determine the independent significance of predictors of all-cause mortality. Results: Age (70 years or older vs. younger), Gleason score (8–10 vs. 7 or lower) and the number of involved nodes (3 or more vs. 1–2) were identified as independent predictors of all-cause mortality. When patients with 0–1 of these risk factors were compared with those with 2–3 risk factors, all-cause (rates after 10 years 21% vs. 71%, p < 0.0001), disease-specific (12 vs. 37%, p = 0.009) and competing mortality (9 vs. 33%, p = 0.02) differed significantly. Conclusions: Some of the excess mortality in patients with poor-risk lymph node-positive prostate cancer may be attributed to increased competing mortality, possibly caused by an interaction between comorbid diseases and hormonally treated persistent or progressive prostate cancer. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

There is increasing interest in the use of adjuvant hormonal therapies, which are given after the resection or destruction of all gross disease, in early-stage prostate cancer, as a significant proportion of patients experience progression and/or die from the disease despite undergoing therapy with curative intent. Several retrospective studies suggest that adjuvant hormonal therapy may improve long-term outcome after radical surgery in men with positive lymph nodes, although this approach has yet to be studied in a prospective setting. No studies of adjuvant therapy for patients with extracapsular extension at surgery have been completed, but in an interim analysis of an open controlled trial, adjuvant flutamide significantly improved progression-free survival at 4 years. Three prospective studies in the radiotherapy setting have shown that adjuvant luteinizing hormone-releasing hormone (LH-RH) agonist therapy significantly improves progression-free and/or overall survival. Future studies need to define patient subgroups who will benefit most from adjuvant therapy. The side effects of the different therapeutic options also need to be compared. It is hoped that many of the outstanding questions concerning adjuvant hormonal therapy will be answered by the ongoing Bicalutamide Early Prostate Cancer Programme. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

[ES] El envejecimiento poblacional y su progresión, es un hecho que debe ser abordado para el bienestar sanitario y social futuro, especialmente de las personas mayores, y por extensión, de toda la sociedad. En este sentido, la fragilidad, entendida como el declive progresivo en los sistemas fisiológicos relacionados con la edad, juega un papel clave. El estudio de la fragilidad mediante el Índice Frágil-VIG, permite abordar a los pacientes en la práctica clínica de una manera multidimensional, estableciendo un diagnóstico situacional. La presente tesis se compone de dos partes diferenciadas. Se realiza un análisis no paramétrico mediante el método Kaplan-Meier de las variables sociodemográficas y clínicas, para determinar los factores pronósticos de fragilidad según el Índice Frágil-VIG, de fragilidad según el Short Physical Performance Battery, de dependencia para las actividades básicas de la vida diaria, y de mortalidad. Posteriormente se procede a realizar análisis multivariantes mediante el modelo de regresión de Cox. Para el desarrollo de los modelos, se sigue la estrategia sugerida por Collett. Previamente, se realiza la validación del Índice Frágil-VIG respecto al Short Physical Performance Battery. Respecto al análisis no paramétrico, fueron factores pronósticos de fragilidad según el Índice Frágil-VIG el estado civil, el nivel de cronicidad y el número de convivientes; factores pronósticos de fragilidad según el Short Physical Performance Battery el nivel de cronicidad y el Índice Frágil-VIG; factores pronósticos de dependencia para las actividades básicas de la vida diaria el estado civil, la fragilidad según el Índice Frágil-VIG y el nivel de cronicidad; y factores pronósticos de mortalidad fueron la dependencia para las actividades básicas de la vida diaria, la fragilidad según el Índice Frágil-VIG, el nivel de estudios, el estado civil, el nivel de cronicidad y el sexo. En el análisis multivariante, las variables incluidas en los modelos de fragilidad según el Índice Frágil-VIG y la dependencia para las actividades básicas de la vida diaria, fueron el estado civil, el nivel de cronicidad y el sexo. En el modelo multivariante de fragilidad según el Short Physical Performance Battery fueron significativas las variables nivel de cronicidad y el número de convivientes. Y finalmente, en el modelo multivariante de mortalidad, resultaron significativas las variables nivel de estudios, el sexo y la fragilidad según el Índice Frágil-VIG. El Índice Frágil-VIG presentó una adecuada validez convergente y discriminativa respecto al Short Physical Performance Battery. Un 20% de las personas difirieron en el diagnóstico de fragilidad entre ambas herramientas, presentando perfiles diferentes. La validación del Índice Frágil-VIG ha fortalecido el uso del mismo para el desarrollo de los modelos. Los grupos de riesgo desarrollados pueden ayudar a establecer estrategias de salud diferenciadas, tanto a nivel individual en la consulta como a nivel poblacional. Con el objetivo de facilitar su implementación en la práctica clínica diaria, se han desarrollado nomogramas que permiten visualizar fácilmente con el objetivo de poder disponer de manera gráfica una herramienta aplicable en la consulta. / [CA] L'envelliment poblacional i la seua progressió, és un fet que ha de ser abordat per al benestar sanitari i social futur, especialment de les persones majors, i per extensió, de tota la societat. En este sentit, la fragilitat, entesa com el declivi progressiu en els sistemes fisiològics relacionats amb l'edat, juga un paper clau. L'estudi de la fragilitat mitjançant l'Índex Fràgil-VIG, permet abordar als pacients en la pràctica clínica d'una manera multidimensional, establint un diagnòstic situacional. La present tesi es compon de dues parts diferenciades. Es realitza una anàlisi no paramètric mitjançant el mètode Kaplan-Meier de les variables sociodemogràfiques i clíniques, per a determinar els factors pronòstics de fragilitat segons l'Índex Fràgil-VIG, de fragilitat segons el Short Physical Performance Battery, de dependència per a les activitats bàsiques de la vida diària, i de mortalitat. Posteriorment es procedix a realitzar anàlisi multivariants mitjançant el model de regressió de Cox. Per al desenvolupament dels models, se seguix l'estratègia suggerida per Collett. Prèviament, es realitza la validació de l'Índex Fràgil-VIG respecte al Short Physical Performance Battery. Respecte a l'anàlisi no paramètric, van ser factors pronòstics de fragilitat segons l'Índex Fràgil-VIG l'estat civil, el nivell de cronicitat i el nombre de convivents; factors pronòstics de fragilitat segons el Short Physical Performance Battery el nivell de cronicitat i la fragilitat segons l'Índex Fràgil-VIG; factors pronòstics de dependència per a les activitats bàsiques de la vida diària l'estat civil, la fragilitat segons l'Índex Fràgil-VIG i el nivell de cronicitat; i factors pronòstics de mortalitat van ser la dependència per a les activitats bàsiques de la vida diària, la fragilitat segons l'Índex Fràgil-VIG, el nivell d'estudis, l'estat civil, el nivell de cronicitat i el sexe. En l'anàlisi multivariant, les variables incloses en els models de fragilitat segons l'Índex Fràgil-VIG i la dependència per a les activitats bàsiques de la vida diària, van ser l'estat civil, el nivell de cronicitat i el sexe. En el model multivariant de fragilitat segons el Short Physical Performance Battery van ser significatives les variables nivell de cronicitat i el nombre de convivents. I finalment, en el model multivariant de mortalitat, van resultar significatives les variables nivell d'estudis, el sexe i la fragilitat segons l'Índex Fràgil-VIG. L'Índex Fràgil-VIG va presentar una adequada validesa convergent i discriminativa respecte al Short Physical Performance Battery. Un 20% de les persones van diferir en el diagnòstic de fragilitat entre totes dues eines, presentant perfils diferents. La validació de l'Índex Fràgil-VIG ha enfortit l'ús del mateix per al desenvolupament dels models. Els grups de risc desenvolupats poden ajudar a establir estratègies de salut diferenciades, tant a nivell individual en la consulta com a nivell poblacional. Amb l'objectiu de facilitar la seua implementació en la pràctica clínica diària, s'han desenvolupat nomogrames que permeten visualitzar fàcilment amb l'objectiu de poder disposar de manera gràfica una eina aplicable en la consulta. / [EN] Population aging and its progression is a fact that must be addressed for the future health and social well-being, especially of the elder people, and by extension, of society as a whole. In this sense, frailty, understood as the progressive decline in physiological systems related to age, plays a remarkable role. The study of frailty using the Frail Index-VIG allows patients to be approached in clinical practice with a multidimensional view, thus establishing a situational diagnosis. This thesis is composed of two different parts. A non-parametric analysis is carried out using the Kaplan-Meier method of the sociodemographic and clinical variables to determine the prognostic factors of frailty according to the Frail-VIG Index, frailty according to the Short Physical Performance Battery, dependency for basic activities of the daily life, and mortality. Subsequently, multivariate analysis were performed using the Cox regression model. For the development of the models, we follow the strategy suggested by Collett. Previously, validation of the Frail-VIG Index is carried out regarding the Short Physical Performance Battery. Regarding the non-parametric analysis, marital status, chronicity level and number of cohabitants, were prognostic factors for frailty according to the Frail-VIG Index; chronicity level and frailty according to the Frail-VIG Index were prognostic factors for frailty according to the Short Physical Performance Battery; prognostic factors for dependency in basic activities of daily living were marital status, frailty according to the Frail-VIG Index and chronicity level; and mortality prognostic factors were dependency for basic activities of daily living, frailty according to the Frail-VIG Index, educational level, marital status, chronicity level and sex. In the multivariate analysis, the variables included in the frailty models using the Frail-VIG Index and dependency for basic activities of daily living were marital status, chronicity level and sex. In the multivariate model of frailty according to the Short Physical Performance Battery, the variables chronicity level and number of cohabitants were significant. And finally, in the multivariate mortality model, the variables level of education, sex and frailty according to the Frail-VIG Index were significant. The Frail Index-VIG presented adequate convergent and discriminative validity compared to the Short Physical Performance Battery. 20% of participants differed in the diagnosis of frailty between both tools, by presenting different profiles. The validation of the Frail-VIG Index has firmed up its use for the development of models. The risk groups might help to establish differentiated health strategies, both at the individual level in the clinical practice and at the population level. In order to facilitate the clinical practice, we developed nomograms that allow an easy visualization of the different risks. / Camacho Torregrosa, S. (2024). Modelización matemática de la fragilidad valorada mediante el Índice Frágil-VIG y el SPPB, de la dependencia para las actividades básicas de la vida diaria y de la mortalidad en población general de 70 años o más. Validación del Índice Frágil-VIG respecto al SPPB [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/205710