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Extent of inflammation predicts cardiovascular disease and overall mortality in seropositive rheumatoid arthritis. A retrospective cohort study from disease onset.

OBJECTIVE: To identify predictors for cardiovascular disease (CVD) and for overall survival in patients with rheumatoid arthritis (RA) followed from disease onset. METHODS: A retrospective cohort of patients with seropositive RA and disease onset between 1974 and 1978 (n = 211) was followed up at the end of 1995. Potential predictors for CVD, as measured by "the first cardiovascular event," and for overall survival were registered. The predictors were identified by extended Cox regression models. RESULTS: In simple Cox regression analysis, male sex, higher age at disease onset, HLA-B27, high disease activity, corticosteroid treatment early in disease, and hypertension significantly increased risk of cardiovascular event. Higher educational level, extensive disease modifying antirheumatic drug (DMARD) treatment, and corticosteroids > or =1 yr before event decreased the risk. In multiple Cox regression analysis, male sex, high age at disease onset, hypertension, higher haptoglobin level at disease onset, and corticosteroid treatment early in disease increased risk of CVD. In a multiple model comprising only patients with CVD, corticosteroids delayed the event. A high last registered erythrocyte sedimentation rate (ESR) value before event increased CVD risk, in particular when early in disease progression. Decreased life span was predicted by higher age at disease onset, male sex, low education level, high disease activity, hypertension, and CVD. HLA-B27 was associated with decreased life span, as was early, but not extensive corticosteroid treatment. DMARD treatment was associated with decreased mortality risk, as was the presence of joint prosthesis. In multiple regression, male sex, higher age at disease onset, atlantoaxial subluxation early in disease, hypertension, and cardiovascular event increased mortality. A high last registered ESR value before event or death added to that risk. CONCLUSION: The study emphasizes the importance of inflammation as an important risk indicator for CVD and mortality in RA. The positive impact of disease activity reducing treatment on CVD risk and survival is suggested.

Adrenal Cortex Hormones↗

[Non-randomized study on the effects of preoperative radiotherapy and daily administration of low-dose cisplatin against those of radiotherapy alone for oral cancer--effects on local control, control of metastases, and overall survival].

Cisplatin is a known radiation modifier. Our previous study suggested that daily administration of low-dose cisplatin enhanced the efficacy of radiotherapy against primary oral squamous carcinoma. In this paper, we follow the patients who participated in the previous study and survey the benefit of combination low-dose cisplatin in improving local control, prevention of metastases, and overall survival. This study included patients with surgically resectable advanced oral tumors. Ten patients underwent preoperative radiotherapy of 30-40 Gy/15-20 days with concomitant daily administration of low-dose cisplatin (5 mg/body or 5 mg/m2). Ten other patients received external radiotherapy alone. All patients then underwent a planned radical tumor resection. No significant difference was see in loco-regional control rates (primary: 86 vs. 88%, neck: 83 vs. 78% at 48 months) or incidence of metastasis (70 vs. 64%) between the two groups. Nor was there a significant difference in the overall survival rate (60 vs. 66%). The results of this study suggest that the concomitant use of daily administration of low-dose cisplatin with preoperative radiation brings no statistically significant benefit in improving local control and survival rate in patients with advanced resectable oral cancer.

Adult↗

The holistic architectural approach to integrating the healthcare record in the overall information system.

The integration and evolution of existing systems represents one of the most urgent problems facing those responsible for healthcare information systems so that the needs of the whole organisation are addressed. The management of the healthcare record represents one of the major requirements in the overall process, however it is also necessary to ensure that the healthcare record and other healthcare information is integrated within the context of an overall healthcare information system. The CEN ENV 12967-1 'Healthcare Information Systems Architecture' standard defines a holistic architectural approach where the various, organisational, clinical, administrative and managerial requirements co-exist and cooperate, relying on a common heritage of information and services. This paper reviews the middleware-based approach adopted by CEN ENV 12967-1 and the specialisation necessary for the healthcare record based on CEN ENV 12265 'Electronic Healthcare Record Architecture'.

Computer Systems↗

Thymidylate synthase expression: an independent prognostic factor for local recurrence, distant metastasis, disease-free and overall survival in rectal cancer.

Several studies have suggested that the intratumoral level of thymidylate synthase (TS) in colorectal tumors correlates with survival. We have studied the correlation between TS expression in primary rectal cancer and locoregional recurrence, distant metastases, and survival. TS enzyme levels were evaluated immunohistochemically using the specific monoclonal antibody TS 106 in paraffin-embedded tumors from 243 patients who had undergone primary surgery for rectal cancer during the years 1980-1993. All patients were included in prospective randomized trials aimed at determining the clinical value of a short preoperative course of local radiation therapy (five doses of 5 Gy each). With a median follow-up of 94 months (range, 43-202 months), it was observed by multivariate analysis that Dukes' stage and TS expression were independent prognostic markers of locoregional recurrence (P < 0.001 and P = 0.038, respectively) distant metastasis (P < 0.001 and P = 0.011, respectively) disease-free survival (P < 0.001 and 0.014, respectively), and overall survival (P < 0.001 and 0.020, respectively). By multivariate analysis, preoperative irradiation therapy showed a borderline improvement in locoregional recurrence (P = 0.051). No other factors, such as age, sex, differentiation of the tumor, or p53 expression, were noted to be independent prognostic factors for clinical outcome in these patients. We concluded that the intratumoral expression of TS in primary rectal cancer is an independent prognostic factor for locoregional recurrence, distant metastases, disease-free survival, and overall survival. Patients with low intratumoral TS expression had a significantly better outcome than those with high TS expression.

Adenocarcinoma↗

Down-regulation of p27 is a significant predictor of poor overall survival and may facilitate metastasis in colorectal carcinomas.

The p27 gene product has been shown to have prognostic significance in a range of tumors. Down-regulation of p27 has also been implicated in loss of cell adhesion in tumor cells. Our study aimed to investigate whether p27 expression was significantly correlated with overall survival of colorectal carcinoma patients in the Singapore population, which is predominantly Chinese. Staining was performed on 136 paraffin-embedded specimens collected between 1991 and 1992 using an anti-p27 monoclonal antibody. Follow-up of patients was until time of death or for 5 years. There was a significant association between overall survival and p27 expression for all specimens. However, there was no significant correlation between p27 expression and other clinical features such as gender, age, tumor stage, differentiation, and site. When stratified by tumor stage, patients whose tumors exhibited higher metastatic potential (stage III/IV) but had strong p27 expression had a median survival that was 23 months longer than stage III/IV patients whose tumors had no or weak p27 expression. Our results thus suggest that one potential mechanism of action of p27 is to suppress metastasis possibly through its involvement in cell adhesion.

Age Factors↗

Catalysis of a step of the overall reaction by the alpha subunit of Escherichia coli succinyl coenzyme A synthetase.

The isolated alpha subunit or succinyl-CoA synthetase from Escherichia coli is capable of catalyzing one step of the overall reaction, namely its own phosphorylation by the substrate ATP. The data presented herein also suggest that the binding sites for other substrates (succinate, succinyl-CoA) are located either on the beta subunit or comprise part of both subunit types. From these observations and from our earlier finding that the two subunits species are necessary for the overall reaction, we propose that the active site is assembled at or close to the point of contact of the two subunits in the native alpha2beta2 enzymic structure.

Adenosine Triphosphate↗

[Overall genomic DNA methylation in relation to estrogen].

Overall genomic DNA methylation was analyzed using enzymatic digestion into nucleotides, 32P postlabeling, two-dimensional thin-layer chromatography on cellulose plates and phosphobioimaging quantitation, in relation to immunohistochemically measured estrogen (ER) and progesterone receptor (PR) status of 15 uterine cancers. Mean 5-methyldeoxycytosine (m5dC) content did not differ between ER-positive and ER-negative neoplasms. Highest values of m5dC were noted both in ER-negative and ER-positive tumors. Additionally, there was no low DNA methylation in ER negative uterine cancer tissues. Decrease of the overall genomic DNA methylation could be related to the increase of ER/PR ratio, however it was not significant in our investigation. The potential role of steroid receptors status in uterine cancer tissue is discussed.

Aged↗

Supplementation of postmenopausal women with fish oil does not increase overall oxidation of LDL ex vivo compared to dietary oils rich in oleate and linoleate.

Although replacement of dietary saturated fat with monounsaturated and polyunsaturated fatty acids (MUFA and PUFA) has been advocated for the reduction of cardiovascular disease risk, diets high in PUFA could increase low density lipoprotein (LDL) susceptibility to oxidation, potentially contributing to the pathology of atherosclerosis. To investigate this possibility, 15 postmenopausal women in a blinded crossover trial consumed 15 g of sunflower oil (SU) providing 12.3 g/day of oleate, safflower oil (SA) providing 10.5 g/day of linoleate, and fish oil (FO) providing 2.0 g/day of eicosapentaenoate (EPA) and 1.4 g/day of docosahexaenoate (DHA). During CuSO(4)-mediated oxidation, LDL was depleted of alpha-tocopherol more rapidly after FO supplementation than after supplementation with SU (P = 0.0001) and SA (P = 0.05). In LDL phospholipid and cholesteryl ester fractions, loss of n-3 PUFA was greater and loss of n-6 PUFA less after FO supplementation than after SU and SA supplementation (P < 0.05 for all), but loss of total PUFA did not differ. The lag phase for phosphatidylcholine hydroperoxide (PCOOH) formation was shorter after FO supplementation than after supplementation with SU (P = 0.0001) and SA (P = 0.006), whereas the lag phase for cholesteryl linoleate hydroperoxide (CE18:2OOH) formation was shorter after FO supplementation than after SU (P = 0.03) but not SA. In contrast, maximal rates of PCOOH and CE18:2OOH formation were lower after FO supplementation than after SA (P = 0.02 and 0.0001, respectively) and maximal concentrations of PCOOH and CE18:2OOH were lower after FO supplementation than after SA (P = 0.03 and 0.0006, respectively). Taken together, our results suggest that FO supplementation does not increase the overall oxidation of LDL ex vivo, especially when compared with SA supplementation. Consequently, health benefits related to increased fish consumption may not be offset by increased LDL oxidative susceptibility.-- Higdon, J. V., S. H. Du, Y. S. Lee, T. Wu, and R. C. Wander. Supplementation of postmenopausal women with fish oil does not increase overall oxidation of LDL ex vivo compared to dietary oils rich in oleate and linoleate. J. Lipid Res. 2001. 42: 407--418.

Aged↗

The place of spiritual well-being in hospice patients' overall quality of life.

There is an increasing awareness of, and interest in the relationship between spirituality and health. This research examines spiritual well-being as one of six components of hospice patients' overall quality of life. Patients admitted over a four-month period were surveyed, using the Functional Assessment of Cancer Therapy scale (FACT-G), at admission, one month later, three months later, and six months later. Data showed spiritual well-being to be an important contributor to overall quality of life. The article concludes by advocating that providing spiritual care to hospice patients makes good business sense.

Commerce↗

Ten-year follow-up of adolescent-onset anorexia nervosa: psychiatric disorders and overall functioning scales.

The aim of this study was to assess prospectively the long-term outcome in a representative sample of teenage-onset anorexia nervosa (AN) in respect of psychiatric disorders and overall outcome. Fifty-one AN cases, recruited by community screening, with a mean age of onset of 14 years, was contrasted with 51 matched comparison cases at a mean age of 24 years (10 years after AN onset). All 102 cases had been examined at ages 16 and 21 years. At 24 years all probands were interviewed regarding psychiatric disorders (SCID-I) and overall outcome (Morgan-Russell assessment schedule, the GAF). There were no deaths at 10-year follow-up. One in four in the AN group had a persisting eating disorder (ED), including three who still had anorexia nervosa. Lifetime diagnoses of affective disorders and obsessive-compulsive disorder were over-represented in the AN group. Outcome according to Morgan-Russell was poor in 27%, intermediate in 29%, and good in 43%. According to the GAF, half the AN group had a poor psychosocial functioning. These were subjects with either a persisting ED or lifelong problems with social interaction or obsessive-compulsive behaviour. Ten-year outcome of teenage-onset AN is favourable in the majority of cases; most individuals have recovered from their ED and have no other axis I disorder. However, half the AN group reported poor psychosocial outcome, in most cases explained by a persisting ED or chronic obsessive-compulsive behaviour/social interaction problems.

Adaptation, Psychological↗

Post-load glucose measurements in oral glucose tolerance tests correlate well with 1,5-anhydroglucitol, an indicator of overall glycaemic state, in subjects with impaired glucose tolerance.

Using both cross-sectional and longitudinal methods, we investigated the relationship between post-load serum glucose concentration in a 75 g oral glucose tolerance test (OGTT) and overall glycaemic state in subjects with impaired glucose tolerance (IGT). Glycaemic state was assessed by measuring glycated haemoglobin (HbA1c) and the serum concentration of 1,5-anhydroglucitol (1,5-AG). In the cross-sectional study, the concentration of 1,5-AG, while remaining within a normal range, was reduced to a degree proportional to the post-load glycaemic level. Although the correlation between HbA1c and post-load plasma glucose was relatively weak (r=0.281, P<0.001), a significant inverse correlation (r=-0.824, P<0.0001) was found between 1,5-AG and mean post-load plasma glucose concentration in 211 subjects with IGT. Fasting plasma glucose (r=-0.539, P<0.0001) and 2 h plasma glucose (r=-0.621, P<0.0001) were correlated with 1,5-AG less strongly than was post-load glycaemia. Both 1,5-AG and HbA1c were correlated weakly but significantly with the fasting insulin concentration. In the longitudinal study we measured 1,5-AG and mean post-load plasma glucose with an OGTT once yearly for 10 years in 15 subjects with IGT. Strong inverse correlations were seen between 1,5-AG and mean post-load plasma glucose in each subject (range of r values among subjects of -0.584 to -0.978). These findings suggest a close relationship between post-load plasma glucose concentration measured by OGTT and overall glycaemic state in subjects with IGT.

Adult↗

Preprandial combination of lispro and NPH insulin improves overall blood glucose control in type 1 diabetic patients: a multicenter randomized crossover trial.

BACKGROUND AND AIM: While lispro insulin has been reported to lower postprandial blood glucose concentrations, less consistent effects have been shown for glycosylated hemoglobin (HbA1c) levels. Aim of this study was to determine whether pre-meal association of NPH, an intermediate-acting insulin, with lispro improves overall glycemic control in type 1 diabetic patients. METHODS AND RESULTS: Eighty-five type 1 diabetic patients were studied in a multicenter randomized comparative (human regular vs lispro insulin) crossover (3-month) study in which NPH insulin was given as a dinner or bedtime injection and at breakfast and lunch if necessary. The number of injections was kept constant: 42% and 58% of patients injected insulin 3 and 4 times per day, respectively. Fasting and preprandial blood glucose levels were similar, while postprandial levels improved after lispro compared to human regular insulin (breakfast: 8.28 +/- 2.39 vs 9.28 +/- 2.72 mmol/l; lunch: 8.33 +/- 2.67 vs 9.06 +/- 2.67 mmol/l, dinner: 8.06 +/- 2.72 vs 9.28 +/- 2.44 mmol/l, ANOVA: p = 0.003). HbA1c also improved after lispro: 8.1 +/- 0.9 vs 8.3 +/- 0.8%, p < 0.05. The rate of hypoglycemia was similar. Patients showed better acceptance of lispro treatment (p < 0.001). CONCLUSIONS: Lispro improves overall blood glucose control in type 1 diabetic patients without increasing the incidence of hypoglycemia. This can be achieved by an optimal combination of lispro insulin with NPH whenever the time intervals between meals are too long.

Adolescent↗

Does long-term application of granulocyte colony-stimulating factor adversely influence overall survival in patients with ovarian cancer? A clinical study.

The purpose of this study was to investigate the effect of long-term administration of G-CSF with regard to its impact on overall survival of patients with ovarian cancer. We report the results of a non-randomized trial on 64 patients with advanced ovarian cancer treated with 6 cycles of conventional chemotherapy. Chemotherapy comprised carboplatin 400 mg/m2 and epirubicin 70 mg/m2 on day 1 of each cycle and prednimustine 100 mg/m2 on days 3 to 7, every 28 days. Thirty-three patients received CEP chemotherapy with G-CSF support whereas 31 women received CEP chemotherapy alone. The schedule of G-CSF was 5 mg/kg/day subcutanously on days 8 to 21 of each cycle. The severity of reduction in white cells and neutrophil count was significantly different in the two treatment groups (p<0.05), with more toxicity in the non- G-CSF group. G-CSF users had a non significant 0.88-fold lower risk of dying from ovarian cancer (95% CI, 0.48-1.60, p=0.678). In a survival analysis using a Cox proportional hazards model, residual tumor remained as an independent prognostic factor. The increasing amount of residual tumor resulted in a 1.767-fold higher risk (95% CI, 1.23-2.53, p=0.002) of death secondary to the underlying disease. In conclusion, this trial has failed to demonstrate any negative impact on patients' overall survival for the additional use of G-CSF with platinum-based chemotherapy; our results were consistent with the beneficial effects of G-CSF treatment on cytotoxic chemotherapy-induced myelosuppression.

Adult↗

[The role of an overall coronary bed affection in heart remodeling in patients with stenocardia and arterial hypertension].

AIM: To study a possible role of coronary circulation condition in remodeling heart in ischemic heart disease (IHD) patients with hypertension or without it. MATERIAL AND METHODS: The examination (veloergometry, echo-CG and Doppler echocardiography, selective coronaroangiography and left ventriculography) covered 45 hypertensive men with angina of effort functional class III and 69 normotensive patients. Mean age of the patients was 51.8 +/- 1.2 years, duration of the angina 3 to 10 years. RESULTS: Correlation analysis of the data on hypertensive examinees discovered a direct correlation between proportional overall lesion of the coronary arteries, myocardial mass index and left ventricular (LV) index of systolic sphericity, between the sphericity index and myocardial mass index. An inverse correlation--with LV ejection fraction. CONCLUSION: In anginal patients, coronary circulation is an independent factor influencing LV remodeling. With progression of coronary failure remodeling intensifies. In patients with angina arterial hypertension contributes to the same degree to an increase in the personage of overall affection of the coronary bed, LV systolic sphericity index and index of its myocardial mass, forms an integral, global risk of heart remodelling and, later, heart failure.

Angina Pectoris↗

Development of a questionnaire to measure hearing-related health state preferences framed in an overall health perspective.

OBJECTIVES: The objective was to develop the Audiological Disabilities Preference Index (ADPI), a measure to determine health state preferences associated with audiological disabilities. The ADPI consists of a hearing-related health state description, hearing-related health state valuation, and transformation of the latter to the overall health scale. Research questions were: a) to determine the feasibility of ADPI in an older hearing-impaired population; b) to assess gain in health state preference after hearing aid fitting; c) to evaluate the reliability of ADPI using hypothetical health states; and d) to compare the results of ADPI with the EuroQol. METHODS: The ADPI, the marker states, and the EuroQol were administered to 78 first-time hearing aid users before and 12 and 25 weeks after hearing aid fitting. RESULTS: The ADPI was feasible in an older hearing-impaired population (mean age, 69.1 years). After hearing aid fitting, all dimensions of audiological disability improved (p < .001). Change in hearing-specific health state and the latter framed in overall health were 0.27 and 0.12, respectively (p < .001). The mean values of the marker states were stable, but the intraclass correlation coefficients were low. Correlations between ADPI and hearing loss and the EuroQol, respectively, were low, while moderate with hearing aid satisfaction. There was a slight change on the EuroQol visual analog scale, with only an improvement in the feeling dimension (p < .05). CONCLUSIONS: The ADPI provides a practical and useful method to assess hearing-related health state preferences needed for clinical decision making and cost-effectiveness analysis.

Aged↗

Overall results of the BEST study following treatment of patients with mild to moderate acne.

In patients with acne, assurance of satisfaction with therapy is a significant factor in helping patients cope with their condition. Therefore, the BenzaClin (benzoyl peroxide/clindamycin topical gel) Efficacy and Satisfaction Trial (BEST) was developed to evaluate patient satisfaction following 8 weeks of treatment with benzoyl peroxide/clindamycin topical gel in patients with mild to moderate acne who were dissatisfied with their current acne therapy. Additional evaluations included efficacy, evaluated with the Global Acne Grading System (GAGS), and the impact of therapy on the social aspects of living with acne, measured with the Acne Quality of Life (AQOL) scale. Results demonstrated significant improvements for all study variables. Patient satisfaction, which was rated from 0 (not satisfied) to 10 (very satisfied) increased almost 3-fold from baseline to week 8 (P < or = .0001). The mean overall AQOL score also improved significantly by a mean of 2.2 points (P < .0001). Acne severity was reduced to almost half of its baseline value (measured using the GAGS score), indicating a significant treatment effect of benzoyl peroxide/clindamycin topical gel (P < or = .0001). Furthermore, as indicated by the Physician Global Assessment (PGA) performed at week 8, acne improved in 94% of patients. Improved patient satisfaction was most likely related to the significant improvements in both efficacy and quality of life (QOL). Overall results of the study suggest that benzoyl peroxide/ clindamycin topical gel is effective for the treatment of acne in patients who are dissatisfied with their current therapy.

Acne Vulgaris↗

Non-specific effect of measles vaccination on overall child mortality in an area of rural India with high vaccination coverage: a population-based case-control study.

OBJECTIVE: To determine whether vaccination against measles in a population with sustained high vaccination coverage and relatively low child mortality reduces overall child mortality. METHODS: In April and May 2000, a population-based, case-control study was conducted at Ballabgarh (an area in rural northern India). Eligible cases were 330 children born between 1 January 1991 and 31 December 1998 who died aged 12-59 months. A programme was used to match 320 controls for age, sex, family size, and area of residence from a birth cohort of 15 578 born during the same time period. FINDINGS: The analysis used 318 matched pairs and suggested that children aged 12-59 months who did not receive measles vaccination in infancy were three times more likely to die than those vaccinated against measles. Children from lower caste households who were not vaccinated in infancy had the highest risk of mortality (odds ratio, 8.9). A 27% increase in child mortality was attributable to failure to vaccinate against measles in the study population. CONCLUSION: Measles vaccine seems to have a non-specific reducing effect on overall child mortality in this population. If true, children in lower castes may reap the greatest gains in survival. The findings should be interpreted with caution because the nutritional status of the children was not recorded and may be a residual confounder. "All-cause mortality" is a potentially useful epidemiological endpoint for future vaccine trials.

Case-Control Studies↗

Does leukodepletion during elective cardiac surgery really influence the overall clinical outcome?

AIM: We examined the impact of leukocyte filtration during the entire bypass time on postoperative leukocytosis, perioperative hemorrhage and overall clinical outcome in patients undergoing elective cardiac surgery. METHODS: Eighty patients who electively underwent cardiac surgery were randomly allocated to a leukocyte depletion group (n=40) or a control group (n=40). In patients of the leukocyte depletion group an arterial line filter with leukocyte depleting capacity (Pall LG6) was applied instead of a standard arterial line filter. White blood cells and platelet count were estimated preoperatively and at various times postoperatively. Postoperative clinical outcomes were also recorded. RESULTS: Repeated measure analysis of variance between groups showed that leukocyte counts were significantly lower in the depletion group postoperatively (p=0.005) whereas no difference was found in the platelet counts (p=0.37). The catecholamine dose required at the time of weaning from cardiopulmonary bypass and during the first 12 postoperative hours was found to be lower in the leukodepletion group (p=0.027 and p=0.021, respectively). Furthermore leukodepleted patients showed a transient improvement in the oxygenation index (p=0.029) and a shorter period of mechanical ventilation (p<0.001). The incidences of postoperative complications were similar between the groups. No difference was observed in regard to postoperative blood loss (p=0.821) and amount of packed red blood cells required for transfusion during the first 24 hours (p=0.846). The duration of intensive care unit stay and of hospitalization were similar between the groups. CONCLUSION: Leukocyte depletion contributes to early postoperative improvement in heart and lung function but does not influence significantly the overall clinical outcome of patients undergoing elective cardiac surgery.

Cardiac Surgical Procedures↗