Prognostic value of health-related quality of life in elderly patients hospitalized with heart failure.

Purpose: Previous research has shown that poor health-related quality of life (HRQOL) is associated with adverse long-term prognosis in patients with heart failure (HF); however, there have been inconsistencies among studies and not all of them confirmed the prognostic value of HRQOL. In addition, few studies involved elderly patients and most focused on all-cause mortality and HF-related hospitalization as outcomes. The aim of our study was to determine whether HRQOL is a predictor and an independent predictor of long-term cardiac mortality, all-cause mortality, and HF-related rehospitalization in elderly patients hospitalized with HF. Patients and methods: This prospective observational study included 200 elderly patients hospitalized with HF in Serbia. HRQOL was measured using the Minnesota Living with Heart Failure questionnaire (MLHFQ). The median follow-up period was 28 months. The primary outcome was cardiac mortality, and all-cause mortality and HF-related rehospitalization were secondary outcomes. Survival analysis was conducted using the Kaplan-Meier method and Cox-proportional hazards regression. Results: Subjects with poor HRQOL (higher than the median MLHFQ score) had a higher probability of cardiac mortality (P=0.029) and HF-related rehospitalization (P=0.001) during long-term follow-up. Poor HRQOL was an independent predictor of cardiac mortality (HR: 2.051, 95% CI: 1.260-3.339, P=0.004), all-cause mortality (HR: 1.620, 95% CI: 1.076-2.438, P=0.021), and HF-related rehospitalization (HR: 2.040, 95% CI: 1.290-3.227, P=0.002). Conclusion: HRQOL is an independent predictor of long-term cardiac mortality in elderly patients hospitalized with HF. It also independently predicts all-cause mortality and HF-related rehospitalization. HRQOL could be used as a complementary clinical predictive tool in this patient population.

Remodeling of extracellular matrix of the lamina propria in the uninvolved human rectal mucosa 10 and 20 cm away from the malignant tumor.

In recent years, it has been demonstrated that malignancy arises and advances through the molecular interplay between tumor cells and non-malignant elements of the tumor stroma, that is, fibroblasts and extracellular matrix. However, in contrast to the mounting evidence about the role of tumor stroma in the genesis and progression of the malignant disease, there are very few data regarding the uninvolved stromal tissue in the remote surrounding of the tumor. Using the objective morphometric approach in patients with adenocarcinoma, we demonstrate the remodeling of extracellular matrix of the lamina propria in the uninvolved rectal mucosa 10 and 20 cm away from the neoplasm. We show that the representation of basic extracellular matrix constituents (reticular and collagen fibers and ground substance) is decreased. Also, the diameter of empty spaces that appear within the extracellular matrix of the lamina propria is increased. These spaces do not represent the blood or lymphatic vessel elements. Very likely, they reflect the development of tissue edema in the remote, uninvolved lamina propria of the mucosa in patients with the malignant tumor of the rectum. We hypothesize that the remodeling of extracellular matrix in lamina propria of the rectal mucosa may increase its stiffness, modulating the mechano-signal transduction, and thus promote the progression of the malignant disease.

Introduction to verification of the GOHAI instrument for measuring the oral health-related quality of life in patients with dentures using the Serbian preliminary version--A pilot study.

BACKGROUND/AIM: Quality of life related to health should be seen as a multidimensional concept that, in addition to the physical symptoms associated with a disease and treatment, should include physical, psychological and social functioning of a person. The primary objective of this study was to use the Serbian preliminary version of the Geriatric Oral Health Assessment Index (GOHAI) questionnaire in oder to examine the consistency, reliability and stability, as well as an introduction to the verification tool. METHODS: The GOHAI questionnaire with 6-level Likert scale, translated into Serbian, including the relevant oral health characteristics (oral hygiene, required dentures, number of teeth extracted), was filled by five specialists in prosthodontics for 30 randomly selected respondents, before and after the dental prosthetic treatment. Subsequently, in order to measure the reliability of the questionnaire, 27 patients were re-interviewed. RESULTS: The value of Cronbach's Alpha Coefficient (Crα) before the treatment was 0.878, and after the treatment it was 0.788 confirming the internal consistency and stability of the questionnaire. The validity of discriminatory properties of the GOHAI was confirmed by the Spearman's correlation coefficient (r), which was highly significantly associated with oral health characteristics, confirming the high reliability of the measurement. The results of test-retest analysis measured by the individual Pearson's correlation coefficient (r) were in the range of 0.34-0.97, and for the total score r was 0.927, while the Kappa coefficient was 0.63. The correlation analysis of the GOHAI score before the treatment showed that for 10 questions there was a statistically significant correlation of the score with the answers to the questions, and for 6 questions Spearman's r was ≥ 0.7. After the treatment a highly significant correlation of the GOHAI was shown with the answers to 10 questions, while for 5 questions the Spearman's r was > 0.6. The GOHAI average score before the treatment was 19.44 ± 11.12, and after the treatment 2.77 ± 3.83, where the lower value indicates better quality of life. CONCLUSION: The results of this pilot study confirm internal consistency and stability of the Serbian preliminary version of the GOHAI questionnaire and the causal relation between the quality of life and the characteristics of oral health of the patients with dentures. Accordingly, instrument verification is recommended.

Morphometric study of uninvolved rectal mucosa 10 cm and 20 cm away from the malignant tumor.

Recently, many details of the interplay between tumor cells and tumor-associated stromal elements leading to the progression of malignant disease were elucidated. In contrast, little is known about the role of uninvolved stromal tissue in the remote surrounding of the malignant tumor. Therefore, we performed a computer-aided morphometric study of rectal mucosa in samples taken 10 cm and 20 cm away from the malignant tumor during endoscopic examination of 23 patients older than 60 years. The samples of rectal mucosa from 10 healthy persons of corresponding age subjected to diagnostic rectoscopy during active screening for asymptomatic cancer were used as control. All structural elements of the rectal mucosa were studied and the number of nucleated cells in the lamina propria per 0.1 mm² of tissue was assessed. Our study revealed a reduced number of cells in the lamina propria of the rectal mucosa 10 cm and 20 cm away from the tumor lesion in both male and female patients. The decreased mucosal height and increased crypt number were registered in female patients 10 cm away from the tumor. The connective tissue of lamina propria showed a disorderly organization: the collagen fibers were frail, loosely arranged and signs of tissue edema were present. Small blood vessels and capillaries were much more frequently seen than in healthy tissue. Our results demonstrate the complex interactions between the cancer and remote mucosal tissue of the affected organ.

Health-related quality of life in elderly patients hospitalized with chronic heart failure.

BACKGROUND: Chronic heart failure is a very common condition in the elderly, characterized not only by high mortality rates, but also by a strong impact on health-related quality of life (HRQOL). Previous studies of HRQOL in elderly heart failure subjects have included mostly outpatients, and little is known about determinants of HRQOL in hospitalized elderly population, especially in Serbia. In this study, we tried to identify factors that influence HRQOL in elderly patients hospitalized with chronic heart failure in Serbia. METHODS: The study population consisted of 136 patients aged 65 years or older hospitalized for chronic heart failure. HRQOL was assessed using the Minnesota Living with Heart Failure questionnaire. Predictors of HRQOL were identified by multiple linear regression analysis. RESULTS: Univariate analysis showed that patients with lower income, a longer history of chronic heart failure, and longer length of hospital stay, as well as those receiving aldosterone antagonists and digoxin, taking multiple medications, in a higher NYHA class, and showing signs of depression and cognitive impairment had significantly worse HRQOL. Presence of depressive symptoms (P<0.001), higher NYHA class (P=0.021), lower income (P=0.029), and longer duration of heart failure (P=0.049) were independent predictors of poor HRQOL. CONCLUSION: Depressive symptoms, higher NYHA class, lower income, and longer duration of chronic heart failure are independent predictors of poor HRQOL in elderly patients hospitalized with chronic heart failure in Serbia. Further, there is an association between multiple medication usage and poor HRQOL, as well as a negative impact of cognitive impairment on HRQOL. Hence, measures should be implemented to identify such patients, especially those with depressive symptoms, and appropriate interventions undertaken in order to improve their HRQOL.

[Chronic low-grade inflammation, lipid risk factors and mortality in functionally dependent elderly].

BACKGROUND/AIM: It has been proved that a highly sensitive C-reactive protein (hsCRP) can be used as an established marker of chronic inflammation for cardiovascular risk assessment. Since mean values of both low-density cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) decrease during aging, the knowledge that increased hsCRP concentration predicts mortality (Mt) would influence therapy and treatment outcome. The aim of this study was to examine importance of chronic low grade inflammation and its association with lipid risk factors for all-cause Mt in functionally dependent elderly. METHODS: The participants of this longitudinal prospective study were 257 functionally dependent elderly aged 65-99 years. Baseline measurements: anthropometric measurements, blood pressure, fasting plasma total cholesterol (TC), triglyceride (TG), HDL-C, LDL-C, non-HDL-C, hemoglobin Alc (HbA1c) were recorded and different lipid ratios were calculated. Inflammation was assessed by the levels of white blood cells, fibrinogen and hsCRP. The participants with hsCRP grater than 10 mg/L were excluded from the study. The residual participants (77.4% women) were divided into three groups according to their hsCRP levels: a low (< 1 mg/L, n=70), average (1 to 3 mg/L, n=69), and high (3-10 mg/L, n=69) hsCRP group. Associations of all-cause Mt with different risk factors were examined using logistic regression analysis. RESULTS: The hsCRP level showed a significant positive correlation with waist (r = 0.199, p = 0.004) and hip (r = 0.187, p = 0.007) circumferences, body mass index (r = 0.143, p = 0.040) and serum triglyceride level (r = 0.139, p = 0.045) and significant negative correlation with HDL-C (r = -0.164, p = 0.018). Ratios TC/HDL-C and TG/HDL-C were significantly smaller in the low hsCRP group compared to the average hsCRP group (p = 0.019,p = 0.045, respectively) and without significant differences compared with the high hsCRP group. Two years after the baseline examination 22.1% participants died from all-cause Mt. After adjustment for other risk factors, a TC was significantly associated with all-cause Mt only in high hsCRP group: Odds ratio (OR) = 3.71 (95% confidence interval-CI: 1.09-12.63). CONCLUSIONS: In this study a high hsCRP was an important factor to identify functionally dependent elderly at high risk who may have more benefit from agressive lipid lowering treatment.

Old age as a privilege of the "selfish ones".

In the past couple of centuries, scientists proposed great number of aging theories but neither of them appears to be fully satisfactory. In the statistical sense, we are dealing with an even greater challenge because large array of factors affects the aging process. Although at this point the most of these factors are well known, it is the very fact of their innumerability that complicates approaches to the issue at hand. Both in life and in medicine, the cause behind an effect can rarely be unequivocally determined. Thus, it appears that through out human history longevity has been primarily affected by eradication of diseases, especially by eradication of infectious diseases and introduction of the vaccines. For that reason, maybe we should not be referring to this issue as the «fountain of youth¼ but rather as the «vaccine of youth¼. The postulate that genetic instability is the precipitating factor both of aging and cancer has withstood many tests and keeps on being reaffirmed. For this reason, it is legitimate to pose a question of whether long-lived individuals may be those with «selfish¼ genes and more stable genetic material. They certainly cannot avoid aging, but aging in such individuals could be delayed due to steady character of their genome, which is less susceptible to mutations. On the population level, they constitute minority because stable genome would represent an obstacle to successful evolution of the species. If this was not the case, we might not be writing all these texts today.

Morphometric study of healthy jejunal and ileal mucosa in adult and aged subjects.

Small intestine mucosa is often affected with malabsorptive, autoimmune and inflammatory pathological processes. However, morphometric data on the healthy human small intestine mucosa, especially ileum, are scarce. We aimed to obtain histoquantitative data on the healthy jejunal and ileal mucosa and assess the effects of gender and ageing on these parameters. Computer-aided morphometric analysis was performed on 24 jejunal and 25 ileal biopsy samples collected upon routine endoscopy screening of healthy persons with a family history of intestinal malignancy. Subjects were distributed in four groups according to age and sex: adult (<60 years) and elderly (>60 years) males, and adult (<60 years) and elderly (>60 years) females. Results were statistically analyzed with Mann-Whitney U test. Jejunal mucosal thickness was significantly reduced in elderly subjects (p<0.05), especially in elderly females compared to adult ones (p<0.05). Jejunal villi were significantly wider in adult than in the elderly subjects (p<0.05), whereas ileal villi were significantly wider in elderly compared to adult subjects (p<0.01) and in male compared to female subjects (p<0.05). No statistically significant differences were found in other histoquantitative parameters (mucosa epithelium height, crypt numerical density, villous height, crypts and villous perimeter, diameter and epithelium height) of jejunal and ileal mucosa. This study provides complete morphometric data on the healthy human jejunum and the first relevant data on the healthy ileal mucosa, thus representing a valuable morphometric reference for future histoquantitative studies of human small bowel mucosa in both healthy and disease affected individuals.

[Articles on elderly in Serbian medical journals].

INTRODUCTION: Population aging is a feature of all countries in the world. According to statistics, the Republic of Serbia is one of the countries with the majority of the elderly. Taking this into account, are articles on the elderly well represented in domestic medical journals? OBJECTIVE: The aim of the paper was to determine whether there was a sufficient number of articles on the elderly in domestic medical journals. METHODS: The articles on the elderly were searched using search engines in domestic and foreign medical journals for the last 5 years compared with the number of articles on children in the same publications for the same period. RESULTS: In the Serbian Citation Index, 11 articles on the topic of the elderly, and 487 on children were registered. In Srpski arhivza celokupno lekarstvo, there was registered only one article on the topic of the elderly, and 30 on children. In Vojnosanitetskipregled, 2 articles on the elderly and 13 on children were registered (p < 0001). For the last five years, in the New England Journal of Medicine, there were 593 articles on the elderly and 759 articles on children; in the JAMA, there were 63 articles on the elderly and 303 articles on children; and in The Lancet, in the last five years, 46 articles on the elderly and 148 articles on children were published. CONCLUSION: The themes of the elderly were rarely represented in Serbian medical journals.This has reduced the interest of physicians in medical problems of this growing population of patients and further sent them away from making standards in the diagnosis and treatment of the elderly.

Long-term prognosis of patients with early post-infarction angina.

BACKGROUND: Most studies have shown that early post-infarction angina (EPA) implies an unfavorable long-term prognosis among patients with acute myocardial infarction (AMI). However, some studies have failed to establish a link between the occurrence of EPA and increased mortality and recurrent infarction rates. METHODS AND RESULTS: In order to evaluate a long-term prognosis in patients with EPA, we assessed the 5-year prognosis of 80 patients with AMI by the presence or absence of EPA. During the 5-year follow up, the occurrence of death, cardiac death, recurrent infarction, unstable angina, heart failure, revascularization and cardiac events were recorded. A cardiac event was defined as an occurrence of any of the following events: cardiac death, recurrent infarction, unstable angina, heart failure and revascularization. Survival analysis showed no differences between patients with and without EPA in the probability of death (p=NS), cardiac death (p=NS), recurrent myocardial infarction (p=NS) and unstable angina (p=NS). Patients with EPA had a higher probability of developing cardiac events (p=0.0285) and undergoing revascularization procedures (p=0.0188). CONCLUSIONS: EPA increases the risk of patients developing cardiac events and undergoing revascularization procedures, and thereby implies a poor long-term prognosis for patients with AMI.

Bleeding during enoxaparin treatment more common with age over 75 years and severe renal insufficiency.

BACKGROUND: Severe renal insufficiency, defined as a creatinine clearance <30 mL/min, increases the risk for bleeding in elderly patients receiving enoxaparin (enoxaparin sodium) treatment. METHODS: The risk/benefit ratios of enoxaparin and unfractionated heparin (UFH) in patients with acute myocardial infarction (AMI) aged >75 years were determined by investigating the parameters of efficacy (ischaemic event, lethal outcome), safety (bleeding events, renal insufficiency) or both (composite endpoint: ischaemic event or lethal outcome or bleeding event). RESULTS: The study included 113 patients (59 male, 52.2%) with AMI aged >75 years; 36 of these patients received enoxaparin. In the patients who had severe renal insufficiency, bleeding events were more frequent in those receiving enoxaparin than in those patients who received UFH (3 vs 1, respectively; p = 0.024). Irrespective of the presence of renal insufficiency, bleeding events occurred more often in patients who received enoxaparin than in those who received UFH (13 vs 8, respectively; p = 0.007). The composite endpoint showed a nonsignificantly better profile in patients who received enoxaparin than in those who received UFH. CONCLUSION: Although the use of enoxaparin (compared with UFH) and the presence of severe renal insufficiency significantly increased the occurrence of bleeding in patients with AMI aged >75 years, the risk/benefit difference in this population was not significant.

Ageism: does it exist among children?

Ageism is stereotyping and prejudice against individuals or groups because of their age. Robert Butler first used it in 1969, to express a systematic stereotyping and discrimination against elderly people. Available data appears to confirm that attitudes of children to the old age differ from that of adults. The study population consisted of 162 subjects (56 school children, 48 nurses and 58 elderly patients). Each subject in the survey was asked to respond to the following three questions: Question #1: "Is the old age unattractive?"; Question #2: "How old is an old man?"; Question #3: "What should you do to have a long life (what is good for longevity)? The majority of polled children (33) gave positive statements about ageing in their responses to the first item, while most of the nurses gave condition answers, like: "It is not unattractive if you are healthy". Elderly subjects made up a group with the majority of negative responses (in percentage), as only 33% of them answered that old age is not unattractive. All three groups of subjects demonstrated a good knowledge of what is considered good for longevity, and had a generally positive health attitude. Our results indicate that majority of children have positive perception and attitude about old age, which leads us to conclusion that ageism is adopted later in life.

Are all dilemmas in gerontology being swept under the carpet of intra-individual variability?

It is considered that there are great differences among elderly individuals, because the intra-individual variability is great. The differences among specific individuals grow with their age, so when adults reach a very old age, it seems that there are great differences among them--some are able to do some work, the others are not so able-bodied, whereas among high school students there is usually little difference in their physical ability. The research that supports the above mentioned points, however, does not exist and this opinion came about as a result of deduction. The goal of this study is to examine the fluctuations in the elderly and prove that the genetic difference plays a bigger role than the variability, as the intra-individual (or the between-person) variability is present everywhere, not only in very old people.

[Autoimmune thyroid disease--clinical symptoms of associated autoimmunity].

Autoimmune diseases are manifested in a broad spectrum. Classic examples of organ-specific autoimmune disease include Addison's disease, insulin-dependent type-1 Diabetes mellitus, Grave's disease (MGB), and Hashimoto thyroiditis (HT). The initial report of this autoimmune thyroid disease (AITD) dates back to Hakira Hashimoto (1912). In HT, as an organ-specific autoimmune disease, massive infiltration of lymphoid cells and parenchyma destruction are a consistent feature. The infiltration appears to be immune-mediated, primarily lymphocytic (T helper, T suppressor cells), NK cells and B cells. The pathological characteristics of AITD include development of the goitre (atrophic form is not so frequent), impaired thyroid gland function (from hyperthyroidism to subclinical and manifested hypothyroidism) and the formation of antithyroidal antibodies against thyroglobulin (AbTg) and the microsomal antigen (Ab TPO). There is a very good correlation between the antibodies against TPO and the histological findings. Morbus Graves Basedow is characterized by autoimmune hyperthyroidism with goitre, and infiltrative orbitopathy. Autoantibodies against the TSH-receptor molecule on the plasma membrane of the thyroid gland follicles cause a nonphysiological activation and an increase of the cellular function. Besides this hyperthyroidal condition, an autoimmune attack against the retrobulbar tissue leading to endocrine orbitopathy, can be noted in about 40% of patients suffering from MGB.

[Subclinical and manifested hypothyroidism as a consequence of thyroid autoimmune disease].

Chronic thyroiditis (Hashimoto's disease) is a slowly developing persistent inflamation of the thyroid gland, which frequently leads to hypothyroidism. Some of the up-to-date knowledge about hypothyroidism, both subclinical and manifested, caused by autoimmune disease, was presented. Autoimmune thyroid gland disease can occur at any age, but predominantly affects women after periods of high emotional and physical stress or accidents, as well as during periods of hormonal changes. It can also develop in families, and having an autoimmune disease slightly increases the risk of developing another. This paper showed an increasing incidence of subclinical hypothyroidism (4.17%) in elderly, and, at the same time, the incidence of primary hypothyroidism accounting for 1%. It is very usefull to estimate the stimulated thyrotropin (TSH) response, as well as the value of fast, short time thyroid gland reserves, analyzed by T3 and T4 serum level at 60th minute after TRH stimulation. Treatment of choice for HT (hypothyroidism of any cause) is thyroid hormone replacement. Drug of choice is orally administered levothyroxine sodium, usually for life-time. The standard dose is 1.6-1.8 mcg/kg body weight per day, but is in most cases patient dependent. Elderly patients usually require smaller replacement dose of levothyroxine, sometimes less than 1 mcg/kg body weight per day with coronary dilatator at the same time.

[Dilated cardiomyopathy associated with autoimmune disease of thyroid gland].

Congestive heart failure is the main cause of cardiovascular morbidity and mortality with more than one million hospitalizations per year. Dilated cardiomyopathy is one of the main causes of congestive heart failure characterized by diminished function of the left, right or both ventricles and ejection fraction less than 40%. Numerous studies reported that the diseases of thyroid gland among the patients with dilated cardiomiopathy were very frequent: with prevalence from 18% to 49%. The impaired thyroid gland function was found as primary cause of cardiomyopathy in 1% of patients. At the same time, among patients with terminal dilated cardiomyopathy, euthyroid sick syndrome was very frequent with low values of T3. According to our results, 29.4% of patients with dilated cardiomyopathy also had autoimmunity disorder of thyroid gland with present antithyroglobin and antimicrosomal antibodies. These patients had lower ejection fraction and worse prognosis. In American College of Cardiology/American Heart Association guidelines for the evaluation and treatment of the congestive heart failure, evaluation of thyroid gland function was recommended; but the evaluation of antitireoglobulin antibodies and free T3 and free T4 was also essential, as was calculation of their ratio. This is the way to discover the autoimmunity disorder of thyroid gland and/ or "euthyroid sick syndrome". In patients with dilated cardiomyopathy and low-T3 syndrome, short-term administration of thyroid hormones resulted in improvement of ejection fraction, diminishing of symptoms and better survival.

[Autoimmune haemopoietic disturbances simultaneous with autoimmune thyroid diseases].

Out of 362 patients with diagnosis of autoimmune haemopathy treated in eight-year period at the Hematology centre, concomitant autoimmune thyreoideopathy was confirmed in 22 (5.52%). The most frequent was simultaneous manifestation of pernicious anemia and autoimmune thyreoiditis-Phenomenon was less frequently observed in patients with immune thrombocytopenic purpura and Graves disease. In the subgroup of patients with autoimmune hemolytic anemia, there was no evidence of simultaneous autoimmune thyreoideopathy. General opinion is that etiopathogenesis of these immunological disorders does not include unique mechanism of humoral and cellular immune response; more probable, it is the question of normal immune response regulation impairment, based on the paerticular genetic predisposition.