Reference intervals are important estimates used to determine whether an individual is healthy or unhealthy. They are the most widely used decision making tool in medicine and heavily influence doctor’s decisions regarding patient care. Despite the abundance of reference interval research in the field of clinical chemistry, age-related reference intervals have yet to be well-established for elderly populations. Many physiological and biochemical changes have been documented to occur with age however limited attempts have been made to quantify these changes. As a result, it is typical in clinical practice to assess geriatric patient data using an adult reference interval. Such practices can result in over-medicalization, unnecessary medical procedures and/or missed diagnoses. This thesis aims to address this gap in literature by summarizing what geriatric reference intervals are available and by investigating how reference intervals are affected by the presence of morbidity, a common characteristic of the elderly. The first chapter of the thesis introduces the reader to reference intervals, summarizes the current guidelines used in their determination and provides a rationale for the use of age-related reference intervals in geriatrics. Chapter 2 presents a systematic review that summarizes all available reference intervals for populations ≥65 years of age and the methodology used in their determination. Despite extreme variability in methodology, evidence suggests that geriatric reference intervals are significantly different from those of adults for many analytes. Chapter 3 presents a study that evaluates the effect morbidity has on reference intervals. In this study data from the National Health and Nutrition Examination Survey (NHANES) was used to calculate age-specific reference intervals for creatinine, a marker of kidney function known to increase with age. Findings suggest that the presence of morbidity significantly increases the upper limit for creatinine in elderly populations. Finally, the concluding chapter summarizes the overall findings of the thesis, proposes areas for future research and reinforces the importance of the above findings. / Thesis / Master of Science (MSc) / Reference intervals are estimates used to determine whether an individual is healthy or unhealthy. In particular this thesis investigates reference intervals for blood test results. Currently no age-specific reference intervals for the elderly are used clinically, instead the normalcy of a blood test result for an elderly person is based on adult reference intervals. This process may lead to over-medicalization or missed diagnoses in geriatrics. Within this thesis is a systematic review of the literature that was performed to capture any available reference intervals that have been published for populations greater than 65 years of age. It was determined that a multitude of geriatric reference intervals are available in literature but they are not used clinically and have no standardized methodology for their determination. Despite this lack of standardization, studies proved that geriatric reference intervals are significantly different from those of adult populations. Given that morbidity or the presence of disease is common in older patients it was suspected this may be a reason for the difference in reference intervals. A separate study was then performed to determine whether the presence of disease affects reference interval calculations. Results from this study showed that the presence of disease affects reference intervals in older individuals more so than younger individuals.

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Thesis (Ed.D.) -- Teachers College, Columbia University, 1991. / Typescript; issued also on microfilm. Sponsor: Seymour Rigrodsky. Dissertation Committee: Eleanor B. Morrison. Includes bibliographical references: (leaves 82-87).

Thesis (M.G.S.)--Miami University, Dept. of Sociology and Gerontology, 2004. / Title from first page of PDF document. Includes bibliographical references (p. 45-49).

In 2009, two large genome wide association studies (GWAS) found associations between common single nucleotide polymorphisms (SNPs) at three loci (CLU, PICALM and CR1) and Alzheimer’s disease (AD) risk. The causal variants underlying these associations and how these impact on AD susceptibility remain unclear. Target enrichment and next generation sequencing (NGS) were used to completely resequence the three associated loci in 96 AD patients in an attempt to uncover potentially causative and rare variants that may explain the observed association signals. A pipeline was developed for the handling of pooled NGS data following a comparison of several different combinations of programs. 33 exonic SNPs were found within the three genes, along with over 1000 non-coding variants. To identify the variants most likely to be affecting AD risk, a two pronged approach was adopted. The variants were imputed in a large case-control cohort (2067 cases, 7376 controls) to test for association with AD, and the likely functional consequences of the variants were assessed using in silico resources. Several of the analysed variants showed suggestive or significant association with AD in the imputed data, and/or were predicted to have consequences on the function or regulation of the genes, suggesting avenues for future research in AD genetics. The whole method of pooled, targeted NGS and prioritisation using imputed data for association testing and in silico resources for functional analysis represents a new strategy for tracking down the illusive causation of GWAS signals.

This thesis explores doctors’ and medical students’ attitudes toward older patients in UK hospital settings. There have been regular and strong assertions in the grey literature and the news media that negative attitudes toward older patients may contribute to the inequality of healthcare service provision and treatment for older patients, compared to younger patients (those aged under 65 years), in UK hospital settings. However, much of the evidence does not investigate or explore these attitudes using a theoretical framework of attitudes outlined in the scientific research literature. This thesis comprises three studies. Firstly, a systematic search and review (Study 1) was undertaken in order to determine how attitudes toward older patients had been explored to date in the English-language, scientific research literature. Results demonstrated that previous studies had focused on attitude measurement rather than exploring the content of attitudes toward older patients. In fact, there was little evidence that previous research had ever explored these attitudes, despite the number of studies attempting to measure them. Furthermore, the review indicated the lack of research emanating from UK settings. In Study 2, attitudes toward older patients and their care were explored in twenty-five in-depth interviews with medical students and doctors in a UK NHS Hospital trust. Data were thematically analysed and findings indicated that attitudes toward older patients and their care could be conceptualised as: (1) attitudes toward older patients and their healthcare needs, and (2) attitudes toward providing care for older patients (e.g. the social and organisational barriers and facilitators). Within these two domains, the themes, subthemes and nodes, which represent attitude content with increasing levels of specificity, are presented. The findings from Study 2 mark one of the first attempts in this research area to explore and describe the content of attitudes in line with a theoretical framework of attitudes. The final study, Study 3, explored the devaluation and unpopularity of the specialty of geriatric medicine as a future career choice in a sample of junior doctors. Having identified, in Study 2, that geriatric medicine was not highly regarded in a range of doctors and medical students, Study 3 aimed to ascertain whether this was due to the organisational and working environment or due to older patient-related factors in a recently-qualified sample of doctors. The findings indicated that organisational and work-related factors serve to discourage junior doctors from pursuing geriatric medicine, rather than factors related to the older patients treated on geriatric wards. This thesis contributes to the research literature in two main ways. Firstly, this thesis outlines the research gaps in the worldwide English-language scientific research. Secondly, this thesis presents a conceptualisation of doctors’ and medical students’ attitudes toward older patients in a UK hospital setting. Importantly, this conceptualisation provides research that is relevant to UK settings and is in line with a theoretical framework of attitudes that has been identified from the scientific research literature. The strengths and limitations of this work are discussed.

In later life, adverse life events, disability, health problems, inadequate social support, and personality traits hypothesized to be important risk factors for depression. Sample included 35 older (65-84) physical rehabilitation patients in a large metropolitan hospital. Statistical analysis included Pearson Product Moment correlations and multiple regression results. Perceived physical health, instrumental ADLs, life satisfaction, extraversion, and conscientiousness are inversely related to depressive symptom severity; neuroticism is positively related to depressive symptom severity. Regression models predicted depressive symptom severity, PANAS negative effect and PANAS positive affect. Neuroticism, insrumental ADLs, and age are significant predictors of depressive symptom severity; neuroticism and age are signficant predictors of PANAS negative affect, while extraversion is a significant predictor of PANAS positive affect. Personality factors, level of functioning, and age are important factors relating to mood. Limitations of this study include: small sample size with special characteristics (high level of SES); incomplete personal and family history of psychiatric problems; and lack of clinical comparison sample.

Mastitis represents a major issue within the dairy industry responsible for economic loss via decreased animal productivity and associated veterinary costs. Currently, there is a push to identify a phenotypic innate immune response that will yield dairy cows with an enhanced resistance to mastitis. Bovine dermal fibroblasts were used as a cell model to measure the response of individuals to Gram-negative bacterial stimuli through the TLR4 signaling pathway. Fibroblast cultures were isolated from 15 dairy heifers at 5, 11, and 16 months of age in order to determine the variability in responsiveness to LPS as well as to monitor the development of the innate immune response in calves. These individuals displayed a large range in response to LPS as measured by IL-8 production. In addition, response within individuals increased dramatically with age. To determine the cause behind this, DNA methylation was investigated as a potential player in the variation in response described both within an individual over time as well as across individuals. Fibroblast exposure to 5-aza-2'-deoxycytidine, a DNA demethylating agent, increased the cellular response to LPS, but more so in cultures that had previously displayed low responding phenotypes. This suggested that DNA methylation acted as an inhibitor of the innate immune response, and may be responsible for some degree of the variation seen in the LPS response. To determine the effect of epigenetic factors on this response, microarray analysis was conducted on RNA isolated from cells either having been epigenetically modified (DNA demethylation and histone hyperacetylation) or without undergoing any epigenetic treatment. This analysis identified 1,758 genes with altered expression due to epigenetic modification. To focus on DNA methylation's role, methylated CpG island recovery assay (MIRA-Seq) libraries were created from fibroblasts to investigate differential methylation from a group of the same individuals sampled at 5 and 16 months of age. In addition, transcriptomic data were generated by RNA-Seq from fibroblasts collected from the young and older samples and exposed to LPS for 0, 2, and 8 hours to characterize age-associated changes in the innate immune response. Cultures from older animals were much more responsive to LPS as indicated by greater expression of IL-8, IL-6, TNF-α, and CCL20 at various times in response to LPS. TLR4 and CD14 were more highly expressed in older cultures, suggesting these fibroblasts are more able to detect the presence of LPS. Analysis of the bovine fibroblast methylome revealed methylation with remarkable stability except for 20 regions along the genome undergoing major shifts due to age. Similar data were collected from fibroblasts isolated from different individuals displaying either a low or high responding phenotype resulting in 843 regions with differential methylation between groups. This suggests that DNA methylation may be playing a role in both the age-dependent and between animal differential responses to LPS, and also gives the first in depth look at the bovine fibroblast methylome and its stability over time.

This correlational study explored the knowledge, perceived seriousness, and willingness to seek medical help for Alzheimer’s Disease (AD) among Ghanaian Immigrants currently residing in the Unites States. Study participants were 163 Ghanaian Immigrants between the ages of 45 and 90, attending Ghanaian community churches in Virginia and Maryland. Significant results include a positive correlation between knowledge and perceived seriousness of the disease, perceived seriousness of the disease was negatively correlated with caregiving experience. These results as well as several seemingly counterintuitive findings are discussed in terms of the Health Disparities and Psychometric challenges. Specifically, these results points to the necessity for future research and implication for action in the following areas: 1) Further qualitative exploration to develop a deep, rich understandings of the phenomenon of AD among Ghanaian Immigrants, 2) Improved cultural sensitivity in psychometric assessment with immigrant populations of AD knowledge, perceptions, and willingness to seek assistance, 3) Person Centeredness and Cultural Humility in Educational Interventions to empower individuals and parallel existing cultural beliefs rather than displacing them.

O traçado eletrocardiográfico, observado durante a anestesia geral, pode diferir morfologicamente do traçado pré-anestésico. O que não se conhece é o grau de influência que os fármacos anestésicos exercem sobre o registro eletrocardiográfico de um cão geriátrico submetido à anestesia geral e a que ponto estas alterações eletrocardiográficas interferem em sua hemodinâmica. Avaliou-se oitenta e dois cães geriátricos (categoria de risco I ou II) foram distribuídos em três grupos: grupo I, cães de pequeno porte (até 10 kg, n=36); grupo II, cães de médio porte (11 a 25 kg, n=27), e grupo III, cães de grande porte (26 a 45 kg, n=19). Além da avaliação eletrocardiográfica, os exames pré-anestésicos constaram de hemograma completo, mensuração sérica de uréia, creatinina, proteína total e albumina; foram feitas mensurações séricas de potássio, cálcio, sódio e magnésio. A medicação pré-anestésica constou de acepromazina associada à morfina ou a meperidina ou somente morfina. A indução foi feita com propofol ou propofol associado ao midazolam, e a manutenção da anestesia realizada com isofluorano em oxigênio a 100%. Durante a anestesia, os cães foram monitorados continuamente com auxílio de um eletrocardiógrafo computadorizado que avaliou o ritmo cardíaco, a freqüência cardíaca, o intervalo PR, a largura e a morfologia do complexo QRS, o segmento ST, a morfologia, a amplitude e a polaridade da onda T. Avaliou-se também a pressão arterial sistólica, média e diastólica; a freqüência respiratória; a ventilação avaliada através da observação da concentração de dióxido de carbono expirado e dos valores de pressão parcial de dióxido de carbono no sangue arterial; a oxigenação, avaliada através da oximetria de pulso, da pressão parcial de oxigênio no sangue arterial e da saturação da oxi-hemoglobina arterial. Os animais foram submetidos à ventilação assistida ou à controlada quando observou-se hipoventilação e hipercapnia. Nos três grupos, o ritmo cardíaco mais freqüente foi o sinusal normal (88%). Observou-se taquicardia sinusal em alguns momentos do trans-operatório em 9% dos animais. Pouco freqüente, mas com importância hemodinâmica, observou-se bradicardia sinusal (3%) associada à hipotensão. Assim, neste estudo o isofluorano não proporcionou o aparecimento de arritmias e promoveu estabilização hemodinâmica dos animais. Observou-se aumento não significante do intervalo PR que do ponto de vista biológico deve ser considerado importante, visto que aproximadamente 11% dos animais que apresentavam intervalo PR normal com ritmo sinusal , evoluíram para bloqueio atrioventricular de primeiro grau. Observou-se bloqueio atrioventricular de primeiro grau em 2% dos animais no eletrocardiograma pré-anestésico, e 1% evoluiu com bloqueio atrioventricular de 2o grau Mobitz tipo I. As alterações no segmento ST e onda T durante o período trans-anestésico, foram muito freqüentes e relacionadas principalmente a hipoventilação. / The electrocardiogram observed during the general anesthesia, can differ from the morfology of the preanesthetic record. It is unknown the influence of the anesthetic drugs in the electrocardiographic record of a elderly dog during general anesthesia, and if electrocardiographic disturbances interfere in their hemodynamic. Eighty two geriatrics dogs (risk category I or II) were evaluated and distributed in three groups: group I, small-size breeds (less than 10 kg, n=36); group II, medium-size breeds (11 to 25 kg, n=27), and group III, large-size breeds (26 to 45 kg, n=19). Beyond electrocardiographic evaluation, the preanesthetic profile consisted in packed cell volume, seric measurement of urea, creatinine, total protein and albumin; the eletrolytes (potassium, calcium, sodium and magnesium). The preanesthetic medication consisted in acepromazine with morphine or meperidine or only morphine. Anesthesia was induced with propofol or propofol with midazolam and maintained with isoflurane in 100% oxygen. During the anesthesia, the animals were monitoried with a continued computadorized electrocardiogram, recording rhythm, heart rate, P-R interval, QRS complex, ST segment and T wave. The systemic blood pressure (systolic, mean and dyastolic), the respiratory rate, the end-tidal carbon dioxide, partial pressure of arterial CO2, the arterial oxygen saturation, the partial pressure of arterial oxygen and oxygen saturation of hemoglobin were evaluated continuously. The animals were submitted to assisted or controled ventilation when hypoventilation and hypercapnia were observed. In the three groups, the normal sinus rhythm was more common (88%). Sinus tachycardia was observed in 9% of the animals. Sinus bradycardia and a decrease in the systemic blood pressure was observed in 3% of the animals. In view of the results obtained it is possible to conclude that, the isoflurane didn\'t provide the observation of arrhythmias and it gave hemodynamic stability. The prolonged P-R interval was observed although of no statistical significance. However it is important, because 11% of the animals that have prolonged P-R interval, developed first degree atrioventricularricular block. First degree AV block was observed in 2% of the animals in the preanesthetic electocardiogram, and 1% developed second degree AV block Mobitz I during the anesthesia. The changes of ST segment and T wave during the anesthetic proceeding was too common and it was related to hipoventilation.