Gao, Ni. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 133-153). / Abstracts also in Chinese. / ACKNOWLEDGEMENTS / TABLE OF CONTENT --- p.1 / LIST OF FIGURES AND TABLES --- p.4 / List of Figures --- p.4 / List of Tables --- p.5 / ABSTRACT --- p.6 / 中文摘要 --- p.9 / ABBREVIATIONS --- p.11 / Chapter CHAPTER 1 - --- BACKGROUND REVIEW AND HYPOTHESIS --- p.13 / Chapter 1.1 --- Overview of Peritoneal dialysis --- p.13 / Chapter 1.2 --- Peritoneal dialysis in Hong Kong --- p.16 / Chapter 1.3 --- Cardiovasular Disease in PD patients --- p.18 / Chapter 1.3.1 --- Arterial disease --- p.21 / Chapter 1.3.2 --- Left ventricular hypertrophy --- p.23 / Chapter 1.4 --- Malnutrition in PD patients --- p.26 / Chapter 1.5 --- Fluid overload in PD patients: a cause and a result of CVD --- p.28 / Chapter 1.5.1 --- Overview --- p.28 / Chapter 1.5.2 --- Fluid overload and residual renal function --- p.29 / Chapter 1.5.3 --- Fluid overload and hypertension --- p.30 / Chapter 1.5.4 --- Fluid overload and malnutrition --- p.32 / Chapter 1.5.5 --- Assessment of fluid status in PD patient --- p.33 / Chapter 1.6 --- Peritoneal transport as the cause of fluid overload --- p.36 / Chapter 1.6.1 --- Structure of peritoneum --- p.36 / Chapter 1.6.2 --- Structural alteration of peritoneal membrane in PD --- p.37 / Chapter 1.6.3 --- Ultrafiltration dysfunction --- p.38 / Chapter 1.6.4 --- Peritoneal transport and outcome of PD patients --- p.40 / Chapter 1.6.5 --- Fluid overload and peritoneal transport --- p.41 / Chapter 1.6.6 --- Peritoneal transport and malnutrition --- p.42 / Chapter 1.6.7 --- Assessment of peritoneal transport --- p.44 / Chapter 1.7 --- Closing the circle: Arterial stiffness as a cause of high peritoneal transport? --- p.47 / Chapter 1.7.1 --- Vascular function and anatomy --- p.47 / Chapter 1.7.2 --- Atherosclerosis --- p.49 / Chapter 1.7.3 --- Atherosclerosis and Endothelial Dysfunction --- p.50 / Chapter 1.7.4 --- Atherosclerosis and Extracellular Matrix --- p.53 / Chapter 1.7.5 --- Arterial stiffness and renal function --- p.54 / Chapter 1.7.6 --- Arterial stiffness in PD --- p.55 / Chapter 1.7.7 --- Arterial stiffness and clinical outcome --- p.55 / Chapter 1.7.8 --- Assessment of arterial stiffness --- p.57 / Chapter 1.8 --- An overall construct --- p.61 / Chapter 1.9 --- Hypothesis --- p.63 / Chapter CHAPTER 2 - --- GENERAL METHODOLOGY --- p.65 / Chapter 2.1 --- Radiographic Parameters of Intravascular Volume Status --- p.65 / Chapter 2.2 --- Pulse Wave Velocity Study --- p.69 / Chapter 2.3 --- Dialysis adequacy study --- p.72 / Chapter 2.4 --- Peritoneal equilibration test (PET) --- p.73 / Chapter 2.5 --- Assessment of nutritional status --- p.75 / Chapter CHAPTER 3 - --- Radiographic Parameters of Intravascular Volume Status as a Prognostic Marker in Chinese Peritoneal Dialysis Patients --- p.77 / Chapter 3.1 --- Introduction --- p.77 / Chapter 3.2 --- Patients and Methods --- p.78 / Chapter 3.3 --- Results --- p.81 / Chapter 3.4 --- Conclusion --- p.90 / Chapter CHAPTER 4 - --- Longitudinal Changes of Radiographic Parameters as the Prognostic Marker of Chinese Peritoneal Dialysis Patients --- p.91 / Chapter 4.1 --- Introduction --- p.91 / Chapter 4.3 --- Results --- p.95 / Chapter 4.4 --- Conclusions --- p.104 / Chapter CHAPTER 5 - --- "The Relation between Arterial Pulse Wave Velocity, Peritoneal Transport Characteristics, and Radiological Parameters of Intravascular Volume Status in Chinese peritoneal dialysis patients" --- p.105 / Chapter 5.1 --- Introduction --- p.105 / Chapter 5.2 --- Patients and Methods --- p.106 / Chapter 5.3 --- Results --- p.110 / Chapter 5.4 --- Conclusions --- p.119 / Chapter CHAPTER 6 - --- DISCUSSION --- p.120 / Chapter 6.1 --- Methodology --- p.120 / Chapter 6.2 --- Results --- p.123 / Chapter 6.3 --- Further Directions of Research --- p.131 / Chapter 6.4 --- Conclusions --- p.132 / REFERENCE --- p.133 / PUBLICATIONS RELATED TO THIS WORK --- p.154 / Index Publication --- p.154 / Abstract --- p.154

A aterosclerose e suas doenças associadas constituem a principal causa de morte no Brasil. Aterosclerose é uma doença inflamatória crônica que atinge a parede das artérias causando bloqueio das mesmas o que eventualmente pode produzir infarto do miocárdio ou acidente vascular cerebral (AVC). A periodontite é uma enfermidade inflamatória causada pelos subprodutos tóxicos que as bactérias produzem quando se colonizam na placa bacteriana. Essa doença é comum em pacientes HIV positivos e o uso de terapia anti-retroviral altamente ativa (HAART) utilizada nesses pacientes ocasiona efeitos adversos, como a lipodistrofia, fato este que pode apressar o ciclo da aterogênese. Assim, existe uma relação entre a presença da aterosclerose e da doença periodontal em pacientes HIV positivos. No entanto, essa relação é pouco estudada na literatura e é o objetivo desse estudo que avaliou 31 pacientes portadores do HIV com diagnóstico de periodontite crônica e 38 pacientes HIV positivos sem periodontite. Ambos os grupos utilizavam a HAART. Nesses pacientes foi avaliado o perfil lipídico (colesterol total, HDL-C, triglicérides, LDL-C), a expressão de anticorpos anti-oxLDL, as concentrações de citocinas séricas (TNF-, IL-1, IL-6 e IL-10) e os dados do hemograma completo, antes e 12 meses após o tratamento periodontal. Os resultados indicaram que os indivíduos com periodontite crônica quando comparados com o grupo controle apresentam níveis plasmáticos aumentados de leucócitos e neutrófilos; e após o tratamento periodontal, as concentrações plasmáticas de TNF-, IL-1 e IgG diminuíram. Assim, vimos que alguns dos marcadores de risco para doenças cardiovasculares diminuem após um plano de reabilitação oral visando o tratamento da doença periodontal em pacientes HIV positivos. Conseqüentemente, sugerimos que a periodontite pode ser um fator de risco para o desenvolvimento da aterosclerose nesses pacientes. / Atherosclerosis and its associated diseases are the leading cause of death in Brazil. Atherosclerosis is a chronic inflammatory disease that affects the wall of the arteries causing blockage that eventually leads to myocardial infarction or stroke. Periodontitis is an inflammatory disease caused by toxic byproducts produced by bacteria that colonize the oral plaque. HIV positive patients commonly present periodontal diseases and the highly active anti-retroviral therapy (HAART) used in these patients lead to side effects such as lipodystrophy which in turn, can speed up the cycle of atherogenesis. Therefore, there is an occult association between the presence of atherosclerosis and periodontal diseases in these patients. However, this correlation is rarely investigated in the literature and was the objective of this study that analysed 30 HIV positive patients with and 39 HIV positive patients without periodontal disease. All the participants were under HAART. Herein we analysed the lipid profile (total cholesterol, HDL-C, triglycerides, LDL-C), the expression of antioxLDL, concentrations of serum cytokines (TNF-, IL-1, IL-6 and IL-10) and full blood test before and 12 months after periodontal treatment. The results showed that individuals with chronic periodontitis presented increased plasmatic levels of leukocytes and neutrophils and after the periodontal treatment, plasmatic levels of TNF-, IL-1 and IgG decreased. Thus, we showed that some of the risk markers for cardiovascular diseases decrease after oral rehabilitation aiming treatment of periodontal disease in HIV positive patients. Therefore, we suggest that periodontites can be a risk factor for the development of atherosclerosis in these patients.

O crescimento do número de idosos na população é uma tendência mundial. Paralelamente a este fenômeno, surge a prevalência das doenças crônicas, dentre elas as Doenças Cardiovasculares (DCVs) que, muitas vezes, requerem internações hospitalares e tratamentos com múltiplos fármacos. A associação de vários fármacos pode acarretar eventos adversos como as interações medicamentosas (IM) que comprometem a eficácia do tratamento e a segurança do paciente. Uma medida que pode evitar algumas das IMs é o ajuste nos horários de administração dos medicamentos, realizado pelo enfermeiro no aprazamento dos horários, evitando a sobreposição de fármacos. Assim, objetivou-se analisar a ocorrência de sobreposições de medicamentos e de IMs potenciais, durante a internação de idosos com DCVs, na clínica médica, em enfermarias da especialidade cardiologia de um Hospital Universitário, do Estado da Paraíba, nos anos de 2010 e 2011. Trata-se de um estudo não experimental, retrospectivo, exploratório e realizado a partir da análise de dados de natureza secundária contidos nos prontuários dos idosos. A coleta de dados foi realizada no período de junho a agosto de 2012. Foram estudados 135 idosos com diagnóstico de DCV, com média de idade de 71,6 anos para as mulheres e 70,7 para os homens, sendo 65% do sexo masculino. A média de dias de internação foi de 15,3 dias (dp=11,7). Em relação ao diagnóstico médico de DCV, 55,6% possuíam hipertensão arterial sistêmica e 40,8%, insuficiência cardíaca. Quanto ao diagnóstico de doenças não cardiovasculares, 42,2% possuíam diabetes mellitus e 23,0%, alguma doença pulmonar. A média de medicamentos prescritos foi de 14,8 (dp=5,8), sendo 59,4% de medicamentos não cardiovasculares e 40,6% de cardiovasculares; houve 59,7% de sobreposições de medicamentos cardiovasculares administrados com outros não cardiovasculares. Quanto aos horários de maiores sobreposições, 39,4% (média 10,3 e dp= 4,9) delas ocorreram no horário das 6 horas e 21,2% (média 5,6 e dp=3,6), no horário das 18 horas. Com relação às IMs, identificaram-se 143 pares de medicamentos com potenciais para interação entre os medicamentos cardiovasculares prescritos, 273 pares entre os medicamentos não cardiovasculares prescritos e 320 pares entre os medicamentos cardiovasculares prescritos e os não cardiovasculares prescritos. O número de sobreposições e o índice de IMs evidenciados neste estudo chamam a atenção para a necessidade de investimentos na capacitação dos profissionais da saúde, envolvidos neste processo, para o monitoramento mais efetivo da terapêutica medicamentosa, pois, mesmo que os idosos não apresentem reações adversas relacionadas às interações, o risco existirá, podendo comprometer sua segurança / The increasing number of elderly people in the population is a global trend. The prevalence of chronic illnesses appears in parallel with this phenomenon, including cardiovascular diseases (CVD), which often demand hospitalizations and treatments that involve multiple drugs. The association of different drugs can cause adverse events, such as drug interactions (DI), which compromise the effectiveness of treatment and patient safety. One measure that can avoid some of the DIs is the adjustment in the drug administration times, which nurses perform in drug scheduling to avoid drug overlapping. Hence, the objective was to analyze the occurrence of drug overlapping and potential DIs during the hospitalization of elderly patients with CVDs in the medical clinical area, at specialized cardiology wards of a University Hospital in the state of Paraíba, Brazil, in 2010 and 2011. A non-experimental, retrospective and exploratory study was undertaken, based on the analysis of secondary data in the elderly patients\' histories. The data were collected between June and August 2012. In total, 135 elderly diagnosed with CVD were studied, with a mean age of 71.6 years for women and 70.7 for men; 65% male. The mean number of hospitalization days was 15.3 (sd=11.7). As regards the medical diagnosis of CVD, 55.6% suffered from systemic arterial hypertension and 40.8% from heart failure. Regarding the diagnosis of non-cardiovascular diseases, 42.2% suffered from diabetes mellitus and 23.0% from a pulmonary disease. The mean number of prescribed drugs was 14.8 (sd=5.8), including 59.4% of non-cardiovascular and 40.6% of cardiovascular drugs; 59.7% of overlapping was found between cardiovascular drugs that were administered with other non-cardiovascular drugs. As regards the most overlapping time, 39.4% (mean 10.3 and sd=4.9) happened at 06h00 and 21.2% (mean 5.6 and sd=3.6) at 18h00. Concerning the DIs, 143 drug pairs with potential interaction between prescribed cardiovascular drugs were identified, as well as 273 pairs between prescribed non-cardiovascular drugs and 320 pairs between prescribed cardiovascular and non-cardiovascular drugs. The number of overlaps and the DI index evidenced in this study highlight the need for investments in the training of the health professionals involved in this process, with a view to the more effective monitoring of the medication treatment as, even if the elderly do not suffer from adverse reactions related to the interactions, the risk exists and can jeopardize their safety

Doenças cardiovasculares podem ocasionar manifestações clínicas graves como infarto agudo do miocárdio e acidentes vasculares trombóticos, constituindo a principal causa de morte no mundo, fato esse que desperta grande interesse da indústria farmacêutica. As causas normalmente estão relacionadas à elevação dos níveis de colesterol e à agregação plaquetária, que acarretam eventos vaso-oclusivos. Entre as alternativas terapêuticas para o controle e prevenção das doenças cardiovasculares podem-se destacar os inibidores da 3-hidroxi-3-metilglutaril coenzima-A redutase (HMG-CoA redutase), popularmente conhecidos como estatinas. A rosuvastatina merece destaque nessa classe de fármacos, devido à maior seletividade e potência na redução dos níveis de colesterol LDL. O ácido acetilsalicílico, antiinflamatório não-esteróide, também representa uma importante alternativa terapêutica para prevenção de doenças cardiovasculares, devido à sua ampla aceitação como inibidor da agregação plaquetária. Considerando seus mecanismos de ação, estatinas e ácido acetilsalicílico podem ser usados em conjunto para a prevenção de doenças cardiovasculares. Face ao exposto e tendo-se em vista a importância dos dendrímeros como transportadores de fármacos na latenciação, o presente trabalho teve como objetivo desenvolver o pró-fármaco dendrimérico potencialmente ativo em doenças cardiovasculares contendo rosuvastatina e ácido acetisalicílico. Diversas metodologias de síntese foram realizadas na tentativa de obtenção do pró-fármaco dendrimérico composto por mio-inositol ou etilenoglicol como foco central, ácido L(-)-málico e etilenoglicol como espaçantes e rosuvastatina e ácido acetilsalicílico como compostos bioativos. Parte dos intermediários propostos foi sintetizada e purificada com sucesso. As maiores dificuldades encontradas foram a purificação dos compostos e a hidrólise seletiva da proteção do ácido málico protegido. Adicionalmente, realizaram-se estudos computacionais para prever a liberação dos fármacos do pró-fármaco dendrimérico. / Cardiovascular diseases can lead to several clinical manifestations such as myocardial infarction and stroke. Those diseases represent the main cause of death globally and this fact triggers a great interest from the pharmaceutical industries. The causes are usually related to high cholesterol levels and platelet aggregation, which are responsible for the vaso-occlusive events. Among the available drug therapy for control and prevention of cardiovascular diseases, the inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase), popularly known as statins, can be highlighted. Rosuvastatin deserves mention in this class of drugs due to its greater selectivity and potency in reducing the levels of LDL cholesterol. Aspirin, a nonsteroidal anti-inflammatory, also represents an important drug therapy for treatment and prevention of cardiovascular diseases, due to its widespread acceptance as a platelet aggregation inhibitor. Considering their mechanism of action, aspirin and statin can be used in association for prevention of cardiovascular diseases. This said and taken into account that dendrimers are important as carriers in prodrug design the purpose of this work was the synthesis of dendrimer prodrugs potentially active in cardiovascular diseases containing aspirin and rosuvastatin. Several synthetic methods have been used with the aim to synthesizing the dendrimer produgs composed of myo-inositol or ethyleneglycol as core, L-(-)-malic acid and ethyleneglycol as spacer groups and rosuvastatin and aspirin as bioactive compounds. Some of the proposed intermediates was synthesized and purified successfully. The main difficulties were purification of compounds and selectivy desprotection of protected malic acid. Additionally, computational studies were performed in order to predict the release of those drugs from dendrimer prodrugs

Ataxia telangiectasia (AT), caused by mutations in the gene encoding ataxia telangiectasia mutated kinase (ATM), is a rare autosomal recessive disorder. AT individuals exhibit neuronal degeneration and are predisposed to cancer. Carriers of this disorder are predisposed to cancer and ischemic heart disease. Heart disease, mostly due to myocardial infarction (MI), is a leading cause of death in the US. Following MI, release of catecholamines in the heart stimulates β- adrenergic receptors (β-AR). Our lab has shown that β-AR stimulation increases ATM expression in the heart and myocytes, and ATM plays an important role in β-AR-stimulated myocardial remodeling with effects on function, fibrosis and apoptosis. Using wild-type (WT) and ATM heterozygous knockout (hKO) mice, this study investigated the role of ATM in the inflammatory, proliferative and maturation phases of infarct healing post-MI. During the inflammatory phase, 1 and 3 days post-MI, a deficiency of ATM resulted in decreased left ventricular dilation as measured by echocardiography. It decreased the number of neutrophils and macrophages in the heart 1 day post-MI. Myocardial fibrosis, expression of alpha-smooth muscle actin (α-sma) and apoptosis were higher in the infarct region of ATM deficient hearts. Akt activation (anti-apoptotic) was lower, while Bax expression (pro-apoptotic) was higher in the infarct region of ATM deficient hearts. During the proliferative phase, 7 days post-MI, ATM deficiency attenuated cardiac dysfunction as measured by echocardiography. ATM deficient hearts exhibited increased fibrosis and expression of α-sma in the infarct region with increased myocyte apoptosis in the border area. During the maturation phase, 14 and 28 days post-MI, ATM deficiency resulted in exaggerated cardiac function. It associated with increased fibrosis, expression of α-sma and decreased cardiac cell apoptosis in the infarct region 28 days post-MI. Myocyte hypertrophy was greater in the non-infarct region during ATM deficiency. ATM deficiency decreased expression of p16 (marker of cell senescence) and activation of proapoptotic protein, GSK-3β. Thus, ATM modulates the remodeling processes of the heart including function, fibrosis, apoptosis and hypertrophy post-MI. ATM (1) delays the inflammatory response post-MI, (2) decreases dilative remodeling during inflammatory and proliferative phases and (3) exaggerates dysfunction during the maturation phase.

Studies have indicated that approximately 30% of people with heart disease experience major depressive disorder (MDD). Despite strong clinical evidence of a link between the two diseases, the neurobiological processes involved in the relationship are poorly understood. A growing number of studies are revealing similar neuroanatomical and neurochemical abnormalities resulting from both depression and heart disease. The locus coeruleus (LC) is a group of neurons in the pons that synthesize and release norepinephrine, and that is known to play a significant role in depression pathobiology. For example, there is evidence that tyrosine hydroxylase (TH) is elevated in the LC in depression. In addition, there is evidence that the LC plays a role in cardiovascular autonomic regulation. The hippocampus is another region that exhibits abnormalities in both depression and heart disease. In this study, the levels of TH in the hippocampus and LC were examined in the guinea pig pressure-overload model of heart disease. TH levels were also measured in the pressure-overload model treated with vagal nerve stimulation, a new investigational therapeutic intervention in heart disease. This study found that there were no changes in TH levels in the LC or the hippocampus of the pressure-overload model or in the pressure-overload model treated with vagal nerve stimulation.

Background: The incidence of cardiovascular disease (CVD) is high in obese people. The potential effects of inadequate calcium intake on CVD are receiving increased attention. We assessed the association between several risk factors for CVD and calcium intake among obese adults. Methods: We investigated 14,856 obese subjects age 20 years or older from the National Health and Nutrition Examination Survey, 1999-2010. ANOVA and Pearson correlation analyses were used to examine if any relationships existed. Simple and multiple linear and logistic regression analyses were conducted to determine the association between risk factors for CVD and calcium intake. Results: After adjusting for energy intake and other potential confounders, systolic blood pressure, diastolic blood pressure, C-reactive protein, glycosylated hemoglobin, and albuminuria were negatively associated with calcium intake at =0.05 level in both linear and logistic regression analyses. Adjusted regression coefficients and ORs did not show a significant relationship between high-density lipoprotein (HDL) and calcium intake. Total cholesterol was negatively associated with calcium intake in continuous form, but no relationshipwas seen between total cholesterol and the calcium intake quartiles form. When comparing low quartile to high quartile, total cholesterol had a weak negative association with calcium intake at =0.1 level. Conclusion: Our study provides evidence that adequate calcium intake could decrease the risks of CVD, such as high blood pressure and high glycosylated hemoglobin, among obese adults. However, calcium intake was not associated with HDL levels. More research is needed to assess the effect of total cholesterol by calcium intake.

Background. The diagnosis of metabolic syndrome is currently based on synthesizing measurements on five different biochemical and anthropometric scales. The logistics involved makes it less than an ideal screening test of cardiometabolic risk. Adipocytokines, c-peptide and ghrelin have emerged as important non-traditional biomarkers for understanding cardio-metabolic risk, and offer potential as tests of cardiometabolic risk. However, optimal sensitivity and specificity cut-offs of non-traditional biomarkers for detecting cardiometabolic risk are scarce, especially in pre-adolescent ethnic minorities. Objective. To assess the efficacy of 7 non-traditional biomarkers for detecting 3 or more cardiometabolic risk factors in pre-adolescent Hispanic children. Methods. The study population consisted of a healthy control group of 23 children and an at-risk group of 15 children aged 2-10 years with 3 or more cardiometabolic risk factors (blood pressure>=90th percentile; waist circumference >=90th percentile; triglycerides>=95th percentile; and HDL<5th >percentile) who were recruited as part of a larger pilot study of metabolic syndrome in Hispanic children receiving well-child care at a community health center in Johnson City, TN, from June 2015 to September 2016. T-test, Mann-Whitney U and Chi-squared tests were used to assess differences in characteristics of the two groups. Spearman’s correlation analysis was used to assess the relationship between biomarkers and cardiometabolic risk factors. ROC analysis and the Youden’s J statistic=maximum (sensitivity +(specificity-1)) were used to determine biomarker cut-off for optimal sensitivity and specificity. Data analysis was performed using SAS 9.4. Results. The mean age of the sample was 6.48 years (SD=2.74). About half of the sample were girls (50.5%). The at-risk group had significantly higher systolic blood pressure, triglyceride levels, waist circumference, leptin and C-peptide levels, but significantly lower HDL-C levels than participants in the control group. Leptin [r (38) = 0.3, p

Background: The misuse and addiction to opioids are one of the major health and social problem that is associated with an increase in morbidity and mortality. Both Buprenorphine (BUP) and Methadone (MET) are FDA-approved treatments for opioid dependence. This longitudinal study is to determine the effects of BUP and MET on hypertension in patients with opioid dependence using a Generalized Estimating Equation(GEE) Model. Methods: The data is from National Drug Abuse Treatment Clinical TrialsNetwork (CTN) protocol CTN-0027. This is a randomized study of 1,934 opioid dependence participants seeking treatment that followed for up to 32 weeks. A total of1,284 males and 631 females participated at the Baseline (visit1) of the study. At the endof 32 weeks (10 visits), 499 males and 243 female patients completed the study. Blood pressure of all the patients was checked at every visit beginning visit 1 to visit 10. For this analysis, the dependent variable was hypertension which was defined as having asystolic blood pressure higher than 140 mmHg and/or a diastolic blood pressure higher than 90 mmHg. These participants were randomly assigned to receive BUP (n= 740) or MET (n= 529). The GEE model with exchangeable correlation was used to determine the efficacy of both the drugs on hypertension. The analysis was performed using PROCGENMOD in SAS 9.4. Results: Time increased the odds of hypertension (adjusted odds ratio (aOR): 1.04, 95% confidence interval (CI): 1.02-1.06, pConclusion: Findings suggest that BUP had a slightly less chance of causing hypertension among patients with opioid dependence comparing with MET controlling for other risk factors, but neither one of Page 54 2017 Appalachian Student Research Forum them had any significant effect on hypertension among patients with opioid dependence. Further analysis will be essential to detect gender x treatment interaction.

Cardiovascular diseases (CVD) and diabetes are the most significant chronic diseases globally due to their high prevalence and mortality. People with CVD or diabetes need to know how to self-manage their health conditions to promote, maintain, and restore their health status. The Nursing Outcomes Classification (NOC) has assisted nurses and other health care providers to evaluate and quantify the status of the patient and has reflected the current health care issues that are to prevent progression of chronic diseases. Based on the current health focus, additional knowledge and self-management NOC outcomes were developed and added to the latest edition of NOC published in 2013. Generally, validation of measurement tools is required to provide trustworthy evidence for use in practice. As measurement tools, NOC outcomes with their definitions, indicators, and measurement scales need to be validated for accuracy, meaningfulness, and usefulness before they are widely used in various health settings. To provide clinical evidence for effective nursing practice such as accurate assessments and evaluations, validation of NOC outcomes is required. The purpose of this study was to validate 12 NOC outcomes focused on knowledge and self-management for people with CVD and diabetes. A descriptive exploratory design was used to validate the selected NOC outcomes, and a two round survey using the Delphi technique was used to collect data from the invited experts via email. Two subject populations were invited. The first expert group was related to standardized nursing languages (SNL) and invited experts were members of NANDA International or a fellow of the Center for Nursing Classification and Clinical Effectiveness (CNC). The second expert group was related to self-management and invited experts were members of two research interest groups which are Health Promoting Behaviors Across the Lifespan and Self Care in the Midwest Nursing Research Society (MNRS). Descriptive statistics were used to determine the definition adequacy, clinical usefulness of measurement scales, and similarity between content of knowledge and self-management outcomes. The Outcome Content Validity (OCV) method was used for the content validity of outcomes and their indicators. A total of 46 and 27 nurse experts participated in the first and second round surveys, respectively. The mean age of participants was 51.87 years (SD=13.03) and the mean of experience in nursing was 27.67 (SD=14.75) years. Most participants had experience using SNL (82.6%). Each outcome reported acceptable psychometric properties. The range of definition adequacy of the 12 NOC outcomes was from 3.71 to 4.29 (perfect score is 5.0). The range of clinical usefulness for using measurement scales was from 3.77 to 4.29. The range of content similarity of the six pairs was from 3.88 to 4.35. Every evaluated NOC outcome identified as critical with over .80 OCV scores (perfect score 1.0). More than 80% of indicators were categorized in the critical level in the first round. Thus, psychometric properties of the 12 NOC outcomes were acceptable to use in the clinical settings. By using validated NOC outcomes, nurses caring of patients with CVD or diabetes can evaluate patient outcomes effectively, and determine the effect of nursing interventions accurately. Development of new NOC outcomes and validation of them will provide nurses with measurement tools to use with patients, clinical evidence for quality improvement and knowledge development in nursing.