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Prevention of sudden death in survivors of myocardial infarction: a decision analysis approach.

During the first year after myocardial infarction, 5% to 15% of patients die, and the majority of deaths occur suddenly. Highly efficacious therapy, such as the implantable cardioverter-defibrillator, may reduce the chance of sudden death, but broad application is limited by associated risks. Hence, attempts to identify patients at high risk so they can receive therapy are desirable. Subgroups with high or low sudden death risks can be identified based on left ventricular function. Further risk stratification using programmed electrical stimulation and the signal-averaged ECG has been advocated, but the best strategy is unknown. Using a decision analysis model, we compared the 1-year survival rates in survivors of myocardial infarction treated with the implantable cardioverter-defibrillator either empirically or based on screening with the signal-averaged ECG and programmed electrical stimulation. The best strategy for selecting patients for therapy depended on the pre-therapy sudden death risk. For patients at low risk, such as those with well-preserved ventricular function, antiarrhythmic therapy selected with screening tests or given empirically increased both the mortality rate resulting from the adverse effects of therapy and the excellent survival rate without therapy. In the moderate-risk population, both empiric and stratified approaches reduced mortality, but stratification substantially limited the number of patients receiving unnecessary therapy. In the high-risk population, empiric treatment achieved the best survival rate, and screening resulted in only a small reduction in the number of patients treated unnecessarily.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Pacing, Artificial↗

The maturation rate of girls living in rich and poor rural regions of Poland before and after the transformation of 1989.

The aim of this study was to find out whether the political and economic system transformation in Poland in 1989 had an influence on the rate of maturation of girls from various categories of the rural population in two regions, differing in wealth. The stratification of the villagers was based on the source of the family income (farmers, farmer-workers and non-farmers), on parents' education, and on the number of children per family. The age at menarche (AM) was used as biological indicator of living conditions. Rural girls aged 9.5-18.5 years were studied in 1987 in Leszno (L), a rich region (n = 2049), and in 1989 in Suwałki (S), a poor region (n = 2077). The study was repeated in 2001 in the same villages, the numbers of subjects amounting to 2440 and 2122, respectively. In the 1980s, AM in regions L and S amounted to 13.18 and 13.88 years, respectively, and was strongly related to social stratification. The earliest AM was found in daughters of non-farmers and the latest in the girls from farmers' families. In 2001, the acceleration in AM amounted to 0.14 years in the rich region and to 0.46 years in the poor region. The percentage of families owning a car, freezer, colour TV and automatic washing machine markedly increased and the education of parents improved. Such results are indicative of an improvement in the living standard of the groups investigated, but the villagers regard themselves as the losers as a result of the system transformation in Poland. Since the Polish population is considered as ethnically homogenous, the great differences in AM within the rural population, as well as the differences between the inhabitants of villages and large cities should be regarded as biological effects of social inequalities. Such differences indicate that Polish rural girls are far below the genetic potential for menarcheal age.

Adolescent↗

Income, social stratification, class, and private health insurance: a study of the Baltimore metropolitan area.

Most studies of inequalities and access to health care have used income as the sole indicator of social stratification. Despite the significance of social theory in health insurance research, there are no empirical studies comparing the ability of different models of social stratification to predict health insurance coverage. The aim of this study is to provide a comparative analysis using a variety of theory-driven indicators of social stratification and assess the relative strength of the association between these indicators and private health insurance. Data were collected in a 1993 telephone interview of a random digit dialing sample of the white population in the Baltimore Metropolitan Statistical Area. Indicators of social stratification included employment status, full-time work, education, occupation, industry, household income, firm size, and three types of assets: ownership, organizational, and skill/credential. The association between social stratification and private health insurance was strongest for those having higher household incomes, having attained at least a bachelor's degree, and working in a firm with more than 50 employees, followed by being an owner or manager, and by being employed. The addition of education and firm size improved the prediction of the household income model. The authors conclude that studies of inequalities in health insurance coverage can benefit from the inclusion of theory-driven indicators of social stratification such as human capital, labor market segmentation, and control over productive assets.

Adult↗

Risk stratification theme for congenital heart surgery.

Surgical practice is changing and auto-evaluation of quality of care, organized by scientific societies, is very likely to become an obligation during this new decade. This evaluation requires a common nomenclature, a registry, and risk stratification. The primary purpose of risk stratification is to offer the possibility of objective analysis of surgical outcomes according to the complexity of the pathology treated. Registries, databases containing select essential data on a complete population, are not able to produce a statistically reliable risk stratification model. Academic databases, like that of the Congenital Heart Surgeons Society, contain comprehensive data on select patients, and are able to produce risk stratification, but only very slowly. The absence of risk discrimination in current registries penalizes centers treating complex pathologies. They may be reluctant to release their results without the security of risk stratification. Given the diversity of congenital heart surgery, a new method has been developed to stratify risks: the complexity score. This approach is based on the perceived opinions of a group of 50 internationally recognized surgeons and centers. It allows a hierarchical classification of surgical procedures according to mortality, morbidity, and surgical difficulty. Surgical procedures are scored globally on simple pathologies and in detail according to seven categories of risks. The complexity score in congenital heart surgery, also known as the Aristotle Score, is currently being developed as a collaborative effort of the members of the European Association for Cardio-thoracic Surgery, the Society of Thoracic Surgeons, the Congenital Heart Surgeons Society, and the European Congenital Heart Surgeons Foundation, and should be available next year.

Databases, Factual↗

Genomic control, a new approach to genetic-based association studies.

During the past decade, mutations affecting liability to human disease have been discovered at a phenomenal rate, and that rate is increasing. For the most part, however, those diseases have a relatively simple genetic basis. For diseases with a complex genetic and environmental basis, new approaches are needed to pave the way for more rapid discovery of genes affecting liability. One such approach exploits large, population-based samples and large-scale genotyping to evaluate disease/gene associations. A substantial drawback to such samples is the fact that population heterogeneity can induce spurious associations between genes and disease. We describe a method called genomic control (GC), which obviates many of the concerns about population substructure by using the features of the genomes present in the sample to correct for stratification. Two such approaches are now available. The GC approach exploits the fact that population substructure generate "overdispersion" of statistics used to assess association. By testing multiple polymorphisms throughout the genome, only some of which are pertinent to the disease of interest, the degree of overdispersion generated by population substructure can be estimated and taken into account. The other approach, called Structured Association (SA), assumes that the sampled population, while heterogeneous, is composed of subpopulations that are themselves homogeneous. By using multiple polymorphisms throughout the genome, SA probabilistically assigns sampled individuals to these latent subpopulations. We review in detail the overdispersion GC. In addition to outlining the published ideas on this method, we describe several extensions: quantitative trait studies and case-control studies with haplotypes and multiallelic markers. For each study design our goal is to achieve control similar to that obtained for a family-based study, but with the convenience found in a population-based design.

Alleles↗

Electron-beam computed tomography: a Bayesian approach to risk assessment.

The epidemic of coronary artery disease continues to affect a large number of individuals who often experience sudden and unexpected events. This underscores the need to develop more effective programs to detect silent atherosclerosis, with the ultimate goal of preventing coronary events. The use of conventional risk factors is helpful in assessing the median risk of a population, but it is often unsatisfactory in estimating the actual risk of an individual patient. As a consequence, newer imaging modalities are being developed to detect atherosclerosis in its early developmental phases. Technologies such as electron-beam computed tomography (EBCT) may render risk stratification more accurate if used in the appropriate patient populations and with the right diagnostic approach. Several studies have already demonstrated the power of coronary calcification as a strong predictor of future cardiovascular events. Nonetheless, the medical literature is currently pervaded by an animated debate, as some investigators still have concerns about the effectiveness of a preventive approach driven by technology. The use of Bayesian models to interpret data acquired with EBCT screening may provide practitioners with valuable evidence to aid in their decision making.

Bayes Theorem↗

Profile of immune cells in axillary lymph nodes predicts disease-free survival in breast cancer.

BACKGROUND: While lymph node metastasis is among the strongest predictors of disease-free and overall survival for patients with breast cancer, the immunological nature of tumor-draining lymph nodes is often ignored, and may provide additional prognostic information on clinical outcome. METHODS AND FINDINGS: We performed immunohistochemical analysis of 47 sentinel and 104 axillary (nonsentinel) nodes from 77 breast cancer patients with 5 y of follow-up to determine if alterations in CD4, CD8, and CD1a cell populations predict nodal metastasis or disease-free survival. Sentinel and axillary node CD4 and CD8 T cells were decreased in breast cancer patients compared to control nodes. CD1a dendritic cells were also diminished in sentinel and tumor-involved axillary nodes, but increased in tumor-free axillary nodes. Axillary node, but not sentinel node, CD4 T cell and dendritic cell populations were highly correlated with disease-free survival, independent of axillary metastasis. Immune profiling of ALN from a test set of 48 patients, applying CD4 T cell and CD1a dendritic cell population thresholds of CD4 > or = 7.0% and CD1a > or = 0.6%, determined from analysis of a learning set of 29 patients, provided significant risk stratification into favorable and unfavorable prognostic groups superior to clinicopathologic characteristics including tumor size, extent or size of nodal metastasis (CD4, p < 0.001 and CD1a, p < 0.001). Moreover, axillary node CD4 T cell and CD1a dendritic cell populations allowed more significant stratification of disease-free survival of patients with T1 (primary tumor size 2 cm or less) and T2 (5 cm or larger) tumors than all other patient characteristics. Finally, sentinel node immune profiles correlated primarily with the presence of infiltrating tumor cells, while axillary node immune profiles appeared largely independent of nodal metastases, raising the possibility that, within axillary lymph nodes, immune profile changes and nodal metastases represent independent processes. CONCLUSION: These findings demonstrate that the immune profile of tumor-draining lymph nodes is of novel biologic and clinical importance for patients with early stage breast cancer.

Adult↗

Nasal carriage of methicillin-resistant Staphylococcus aureus in an American Indian population.

BACKGROUND AND OBJECTIVE: Although reports of methicillin-resistant Staphylococcus aureus (MRSA) infections without healthcare exposure are increasing, population-based data regarding nasal colonization are lacking. We assessed the prevalence of and risk factors for community-associated MRSA nasal carriage in patients of a rural outpatient clinic. DESIGN: A cross-sectional population survey was conducted through random sample and stratification by community of residence. Recent healthcare exposure (ie, hospitalization, dialysis, or healthcare occupation) and other risk factors for MRSA carriage were assessed. Cultures of the nares were performed. Community-associated MRSA was defined as MRSA carriage without healthcare exposure. SETTING: A predominantly American Indian community in Washington. PATIENTS: Those receiving healthcare from an Indian Health Service clinic. RESULTS: Of 1,311 individuals identified for study, 475 (36%) participated. Unsatisfactory culture specimens resulted in exclusion of 6 participants. In all, 128 (27.3%) of 469 participants had S. aureus. Nine (1.9%) of 469 had MRSA carriage; of these, 5 had community-associated MRSA (5 of 469; overall community-associated MRSA carriage rate, 1.1%). MRSA carriage was associated with antimicrobial use in the previous year (risk ratio [RR], 7.2; P = .04) and residence in a household of more than 7 individuals (RR, 4.5; P = .03). Pulsed-field gel electrophoresis indicated that 5 (55%) of 9 MRSA carriage isolates were closely related, including 3 (60%) of 5 that were community associated. CONCLUSIONS: Prevalence of community-associated MRSA colonization was approximately 1% in this rural, American Indian population. Community-associated MRSA colonization was associated with recent antimicrobial use and larger household.

Arizona↗

Differences in body mass index and waist: hip ratios in North Indian rural and urban populations.

Overweight could be a major factor in determining the increasing rates of coronary heart disease in the Indian population, by its influence on blood pressure, diabetes and insulin resistance. We studied the prevalence of overweight in north Indian urban and rural population samples. The urban sample population (n = 3050) was selected using a multistage sampling with stratification for geographical zone and the type of residential colony and cluster sampling of urban blocks in each stratum. The rural sample (n = 2487) was selected by random sampling of villages stratified for population size followed by coverage of all eligible persons in the village. All participating individuals were 35-64 years of age. Women constituted 52.2% (n = 1594) and 57% (n= 1417) of urban and rural samples, respectively. The study reveals that overweight is widely prevalent in the adult urban Delhi population, whereas underweight is a significant problem in the rural population. This was noted across all the age groups in both men and women. We estimated 'comprehensive coronary risk estimates' based on the New Zealand Heart foundation guidelines and noted that the proportion of high and very high risk subjects increased in a continuous manner even within the 'normal' ranges of BMI. This difference in prevalence in the urban population could represent the demographic transition in the Indian population.

Adult↗

Factors associated with prognosis in human breast cancer. III. Estradiol receptors and short term relapse.

Prognosis in breast cancer is one of the most important subjects currently studied because of the heterogeneity of the disease even inside the same clinical stage. Estrogen receptor determination in human breast cancer has been recognized as a prognostic factor since it is related to the long-term survival and disease-free interval. In a series of papers concerning prognosis in breast cancer this the third one which includes estrogen receptor determination in the multivariate analysis, because of the limitations of the clinical factor to conform stratification groups. We have analyzed the short term probability of relapse in a group of 136 patients treated for breast cancer. Multivariate stratification analysis was performed with the aid of Bintree computer program, which produces binary splits of the population according to the criterion of maximal reduction of variance and generates a binary stratification tree. Lymph node involvement is the most important prognostic factor in the probability of relapse. Patients without nodal involvement lacking estradiol receptor had 25% of relapse. It is therefore evident that estradiol receptor is a factor of prognostic value even inside node negative patients.

Breast Neoplasms↗

Geographical stratification by socio-economic status: methodology from a household survey with elderly people in S. Paulo, Brazil.

Considering that in most developing countries there are still no comprehensive lists of addresses for a given geographical area, there has always been a problem in drawing samples from the community, ensuring randomisation in the selection of the subjects. This article discusses the geographical stratification by socio-economic status used to draw a multistage random sample from a community-based elderly population living in a city like S. Paulo-Brazil. Particular attention is given to the fact that the proportion of elderly people in the total population of a certain area appeared to be a good discriminatory variable for such stratification. The validity of the stratification method is analysed in the light of the socio-economic results obtained in the survey.

Aged↗

Sexual and demographic risk factors for herpes simplex virus type 2 according to schooling level among Mexican youths.

BACKGROUND: Herpes simplex virus type 2 (HSV-2), the agent causing one of the most common sexually transmitted infections in sexually active individuals, is currently considered a public health problem. In Mexico, there have been no population-based studies of the prevalence and factors associated with HSV-2 infection among young students. GOAL: The goal was to measure HSV-2 seroprevalence and identify possible associated factors among students in the state of Morelos, Mexico. STUDY DESIGN: Through a cross-sectional population-based study involving students at 92 schools in the state of Morelos, Mexico, 898 students aged 11 to 24 years old were identified. All of them reported they had already initiated sexual activity and provided a blood sample to detect the presence of anti-HSV-2 antibodies through the Western blot technique. The association between risk factors and HSV-2 was evaluated through multiple logistic regression analysis with stratification by sex and schooling level. RESULTS: In the population under study, the prevalence of HSV-2 seropositivity was 5.7% (51/898), and the ratio of females to males was 2:1. The prevalence of consistent condom use overall was 22.6% among the 898 students. For students in Morelos State, Mexico, the HSV-2 seroprevalence was higher among the youngest female students (9.5% among junior high school versus 3.3% among university students; P<0.001). The main factors associated with HSV-2 infection were sex (for females the risk was 2.2 times higher than for males; 95% CI, 1.2-3.9); junior high school status (2.5 times higher risk than university students (95% CI, 1.1-6.0); and having had same-sex sexual intercourse (3.5 times higher risk; 95% CI, 1.4-8.9). CONCLUSION: In contrast with other reports, the HSV-2 seroprevalence was higher among younger people. This finding can be explained by a cohort effect of more exposition to behavioral risks, particularly an earlier age at first intercourse and very low use of condoms among youngest students. Longitudinal surveys about serological responses to HSV-2 infection in different age groups are warranted.

Adolescent↗

Survival and response to chemotherapy for advanced colorectal adenocarcinoma: an Eastern Cooperative Oncology Group report.

A series of 1,314 cases of advanced measurable colon or rectal cancer were evaluated for objective tumor response and survival. All patients received chemotherapy according to protocols conducted by the Eastern Cooperative Oncology Group during the period between 1974 and 1977. For those patients who had not received chemotherapy prior to study entry, no therapy program under evaluations was significantly more active than the oral or intravenous 5-fluorouracil treatment programs with respect to survival or objective tumor response. The survival and response rates therapy programs under study, including methyl-CCNU, appeared to be comparable. Initial performance status (P < 0.01), weight loss in the six months prior to study entry (P < 0.001), and prior chemotherapy status were shown to be most prognostic for survival, and thus merit inclusion as stratification factors in any comparative trial involving this population. These factors were shown to have a cumulatively greater influence upon survival than the treatment program. Treatment differences were most accentuated within the favorable subgroups of the leading prognostic factors. The location of the primary tumor had a significant effect upon the eventual sites of metastatic disease involvement at the time of study entry (P < 0.001). The consequences of this analysis suggest that investigators need to address characteristics of the population under study. It is also noted that patients with chemotherapy prior to study entry are best suited for survival studies, while patients with no chemotherapy prior to study entry are well suited for both objective tumor response and survival studies.

Antineoplastic Agents↗

Breast microcalcifications: multivariate analysis of radiologic and clinical factors for carcinoma.

Screening mammography contributes to the improvement of breast carcinoma survival through early detection and treatment of non-palpable lesions. Microcalcifications are of fundamental importance in this process. The percentage of malignant lesions found in biopsies for microcalcifications varies from 10% to 40%. The purpose of this study was to evaluate the relationship between clinical and radiologic records and the presence of malignant breast diseases. To establish the basis for the study, 211 mammographic files showing clustered microcalcifications from 204 women were prospectively reviewed and clinical records were retrospectively drawn. Definitive pathologic analysis was available for all. The value for cancer of each criterion was investigated by univariate and multivariate analyses. A first analysis was performed on the entire population and a second one was performed with stratification on morphologic subgroups. There were 99 malignant lesions (47%). In the entire group, no clinical criterion was significant. In the univariate analysis, five radiologic variables were significant: morphologic type(p < 0.0001), number of calcifications per cluster(p < 0.0001), linear or triangular distribution(p < 0.0002), diameter of the area (p < 0.01),and number of clusters (p = 0.011). In the multivariate analysis, two criteria remained significant: morphologic type 4 (irregularly punctiform) or 5 (vermicular) microcalcifications(Le Gal's classification) (p < 0.0001) and diameter of the cluster larger than 25 mm (p = 0.032). In subgroups,in the multivariate analysis, the "age > 60 years" criterion was statistically significant in the group of regular punctiform microcalcifications (type 2); for irregularly punctiform microcalcifications (type 4), "number of microcalcifications > 20" was significant. The morphologic features of microcalcifications must be the first criterion evaluated. They permit identification of characteristically benign (annular calcifications) or malignant calcifications (vermicular calcifications). For the remainder of the calcification types, other criteria must be taken into account, and their value vary with (according to) the morphologic aspect. These findings have implications for the management of women with microcalcifications and could help breast specialists make treatment decisions.

Adult↗

Expression of e-cadherin in high-risk breast cancer.

PURPOSE: E-cadherin expression is diverse, and differences in patient characteristics may produce variability in expression. Whereas some studies have indicated that downregulation of e-cadherin, associated with loss of cellular adhesiveness, was correlative with poor prognosis and metastasis, other studies have failed to confirm this. The present study uses a highly homogenous population of patients at high-risk for breast cancer, on the basis of ethnic and socio-economic status, to examine the relationship between e-cadherin and other prognostic markers in breast cancer. METHODS: Immunohistochemical staining was undertaken for estrogen (ER) and progesterone (PR) receptors, epidermal growth factor receptor 2 (Her-2), p53, vascular endothelial factor (VEGF), and hypoxia inducible factor 1alpha (HIF-1alpha) and the levels of these markers was compared to e-cadherin expression in a high-risk African-American patient population. RESULTS: E-cadherin expression persisted into the later stagers of the disease, and was strongly associated with Her-2 and HIF-1alpha expression, but not p53, ER/PR or VEGF. CONCLUSIONS: In contrast to other studies on heterogeneous populations, e-cadherin is preserved in aggressive tumors in this high-risk population. The ethnic and socio-economic risk stratification needs to be accounted for in studies correlating markers and prognosis.

Adult↗

Genome-wide studies of psoriasis susceptibility loci: a review.

Psoriasis is a chronic inflammatory dermatosis affecting approximately 0.3-5% world-wide. Since 1997, nine genome-wide scans have been published in the search for predisposing genes to psoriasis and psoriatic arthritis. These genome-wide scans have provided results that both confirm earlier work, but which also suggest novel regions of interest on the genome. This article reviews the results of these genome-wide scans, in particular two novel regions on chromosomes 3p and 15p, and compares the study types and designs. The results in these two regions were compared in the different studies providing no further suggestive evidence, and we suggest that these results may be false-positives, population-specific susceptibility loci or due to the stratification used in the study design. We suggest stratifying the data into epidemiological subgroups in order to make the genome-wide scans more sensitive to loci specific to these subgroups. This approach could provide a much more powerful technique to study the genetics of a complex disease such as psoriasis.

Genetic Predisposition to Disease↗

Disruption of transient photoreceptor targeting within the inner plexiform layer following early ablation of cholinergic amacrine cells in the ferret.

Photoreceptors in the ferret's retina have been shown to project transiently to the inner plexiform layer (IPL) prior to their differentiation of an outer segment. On postnatal day 15 (P-15), when this projection achieves maximal density, the photoreceptors projecting into the IPL extend primarily to one of two depths, coincident with the processes of cholinergic amacrine cells. The present study has used an excitotoxic approach employing subcutaneous injections of L-glutamate to ablate these cholinergic amacrine cells on P-7, in order to see whether their elimination alters this targeting of photoreceptor terminals within the IPL. The near-complete elimination of cholinergic amacrine cells at P-15 was confirmed, although the population of retinal ganglion cells was also affected, being depleted by roughly 50%. The rod opsin-immunopositive terminals in such treated ferrets no longer showed a stratified distribution, being found throughout the depth of the IPL, as well as extending into the ganglion cell layer. This effect should not be due to the partial loss of retinal ganglion cells, however, since optic nerve transection at P-2, which eliminates the ganglion cells entirely while leaving the cholinergic amacrine cell population intact, was shown not to affect the stratification pattern of the photoreceptors within the IPL. These results strongly suggest that the targeting of the photoreceptor terminals to discrete strata within the IPL is dependent upon the cholinergic amacrine cell processes.

Amacrine Cells↗

Prevalence and incidence of arrhythmias and sudden death in heart failure.

Patients with heart failure are prone to a variety of arrhythmias, symptomatic and asymptomatic, that are prognostically significant and have an important bearing on the management of these patients. However there are some inherent problems in assessing the frequency of these arrhythmias within a large patient population, due to a lack of uniformity in defining heart failure and the transient nature of these rhythms. Patients with heart failure commonly die suddenly. The causes of these deaths are difficult to ascertain accurately and are often presumed arrhythmic. With the advent of effective interventions to prevent sudden death, accurately defining the causal relationship between the arrhythmias and sudden death has assumed great importance to appropriately target therapy. Several attempts have been made to predict such deaths on the basis of non-invasive and invasive diagnostic investigations with variable success. In this article we review the incidence and prevalence of atrial and ventricular arrhythmias and sudden deaths in epidemiological studies, surveys and randomised control trials of patients with heart failure. We discuss the prognostic significance of these arrhythmias, the inherent problems in their diagnosis and whether their presence predicts the risk of sudden deaths and the mode of such deaths in the heart failure population. The role of various investigations in risk stratification of sudden death has also been discussed.

Adult↗