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Nicholas A Christakis

Publications and source records attributed to Nicholas A Christakis.

At least 19 recordsLinked to original sources
PubMed2026

Metagenomic polymorphic toxin effector and immunity profiling predicts microbiome development and disease-related dysbiosis.

Bacteria use antagonistic interbacterial weapons, such as polymorphic toxin secretion systems (TSS), to compete for niches in the human gut microbiome. We hypothesized that TSS influence gut microbiome development and disease-related dysbiosis. We developed a bioinformatic marker gene approach (PolyProf) to quantify TSS including ~200 effector and immunity genes and applied it to ~15,000 publicly available human metagenomes. PolyProf alpha and beta diversity readily distinguished 12 different human disease states and enabled the construction of highly accurate linear regression classifier machine learning models. Elastic net machine learning models integrating bacterial taxonomy with PolyProf had strong predictive value for 12 disease states, outperforming models utilizing taxonomy alone. During microbiome development in the first year of life, PolyProf alpha diversity increases, and beta diversity becomes increasingly like the maternal microbiome, influenced by vertical transfer, delivery mode, and breastfeeding. PolyProf is related to strain sharing among adults through social interactions. In summary, TSS genes strongly correlate with microbiome development and interpersonal strain sharing, suggesting roles for interbacterial antagonism. Since PolyProf distinguishes diverse adult disease statuses, these dynamics may contribute to non-genetic inheritance.IMPORTANCEPrevious research has demonstrated that bacteria compete within the gut microbiome using toxin secretion systems (TSS). How TSS contribute to human microbiome development and the microbiome alterations observed in human diseases is not known. This study develops a new bioinformatic tool for profiling TSS-related genes in metagenomic data. Application of this approach to large-scale human fecal metagenomic data demonstrates the dynamic association of TSS during microbiome development, including the exchange of strains among social contacts. TSS gene abundance patterns are highly predictive of 12 disease states. This study advances the field by enabling TSS profiling in metagenomes and by identifying disease and microbiome development biomarkers that provide hypotheses for future mechanistic studies and may be useful for disease diagnosis.

Dysbiosis↗
PubMed2006

Measuring disease-free survival and cancer relapse using Medicare claims from CALGB breast cancer trial participants (companion to 9344).

To determine the accuracy with which Medicare claims data measure disease-free survival in elderly Medicare beneficiaries with cancer, we performed a criterion validation study. We merged gold-standard clinical trial data of 45 elderly patients with node-positive breast cancer who were treated on the Cancer and Leukemia Group B (CALGB) adjuvant breast trial 9344 with Centers for Medicare and Medicaid Services (CMS) data files and compared the results of a CMS-based algorithm with the CALGB disease-free survival information to determine sensitivity and specificity. For 5-year disease-free survival, the sensitivity of the CMS-based algorithm was 100% (95% confidence interval [CI] = 81% to 100%), the specificity was 97% (95% CI = 83% to 100%), and the area under the receiver operator curve was 98[corrected]% (95% CI = 95[corrected]% to 100%). For 2-year disease-free survival, the test characteristics were less favorable: sensitivity was 83% (95% CI = 36% to 100%), specificity was 95% (95% CI = 83% to 100%), and area under the receiver operator curve was 89[corrected]% (95% CI = 72[corrected]% to 100%).

Aged↗
PubMed2006

Mortality after the hospitalization of a spouse.

BACKGROUND: The illness of a spouse can affect the health of a caregiving partner. We examined the association between the hospitalization of a spouse and a partner's risk of death among elderly people. METHODS: We studied 518,240 couples who were enrolled in Medicare in 1993. We used Cox regression analysis and fixed-effects (case-time-control) methods to assess hospitalizations and deaths during nine years of follow-up. RESULTS: Overall, 383,480 husbands (74 percent) and 347,269 wives (67 percent) were hospitalized at least once, and 252,557 husbands (49 percent) and 156,004 wives (30 percent) died. Mortality after the hospitalization of a spouse varied according to the spouse's diagnosis. Among men, 6.4 percent died within a year after a spouse's hospitalization for colon cancer, 6.9 percent after a spouse's hospitalization for stroke, 7.5 percent after a spouse's hospitalization for psychiatric disease, and 8.6 percent after a spouse's hospitalization for dementia. Among women, 3.0 percent died within a year after a spouse's hospitalization for colon cancer, 3.7 percent after a spouse's hospitalization for stroke, 5.7 percent after a spouse's hospitalization for psychiatric disease, and 5.0 percent after a spouse's hospitalization for dementia. After adjustment for measured covariates, the risk of death for men was not significantly higher after a spouse's hospitalization for colon cancer (hazard ratio, 1.02; 95 percent confidence interval, 0.95 to 1.09) but was higher after hospitalization for stroke (hazard ratio, 1.06; 95 percent confidence interval, 1.03 to 1.09), congestive heart failure (hazard ratio, 1.12; 95 percent confidence interval, 1.07 to 1.16), hip fracture (hazard ratio, 1.15; 95 percent confidence interval, 1.11 to 1.18), psychiatric disease (hazard ratio, 1.19; 95 percent confidence interval, 1.12 to 1.26), or dementia (hazard ratio, 1.22; 95 percent confidence interval, 1.12 to 1.32). For women, the various risks of death after a spouse's hospitalization were similar. Overall, for men, the risk of death associated with a spouse's hospitalization was 22 percent of that associated with a spouse's death (95 percent confidence interval, 17 to 27 percent); for women, the risk was 16 percent of that associated with death (95 percent confidence interval, 8 to 24 percent). CONCLUSIONS: Among elderly people hospitalization of a spouse is associated with an increased risk of death, and the effect of the illness of a spouse varies among diagnoses. Such interpersonal health effects have clinical and policy implications for the care of patients and their families.

Aged↗
PubMed2006

"Are you at peace?": one item to probe spiritual concerns at the end of life.

BACKGROUND: Physicians may question their role in probing patients' spiritual distress and the practicality of addressing such issues in the time-limited clinical encounter. Yet, patients' spirituality often influences treatment choices during a course of serious illness. A practical, evidence-based approach to discussing spiritual concerns in a scope suitable to a physician-patient relationship may improve the quality of the clinical encounter. METHODS: Analysis of the construct of being "at peace" using a sample of patients with advanced cancer, congestive heart failure, or chronic obstructive pulmonary disease. Descriptive statistics were used to compare response distributions among patient subgroups. Construct validity of the concept of being "at peace" was evaluated by examining Spearman rank correlations between the item and existing spirituality and quality-of-life subscales. RESULTS: Variation in patient responses was not explained by demographic categories or diagnosis, indicating broad applicability across patients. Construct validity showed that feeling at peace was strongly correlated with emotional and spiritual well-being. It was equally correlated with faith and purpose subscales, indicating applicability to traditional and nontraditional definitions of spirituality. CONCLUSIONS: Asking patients about the extent to which they are at peace offers a brief gateway to assessing spiritual concerns. Although these issues may be heightened at the end of life, research suggests they influence medical decision making throughout a lifetime of care.

Adult↗
PubMed2006

Prospective effect of community distress and subcultural orientation on mortality following life-threatening diseases in later life.

We conducted a prospective and contextual study to examine the effects of community social-economic-physical distress and subcultural orientation on mortality following onset of 13 life-threatening diseases in later life. We also examined the inter-relationship between the effects of community social, economic and physical distress (i.e. poverty, physical disorder and low collective efficacy) and subcultural orientation (i.e. anomie and tolerance of risk behaviour) on the survival chances of seriously ill older patients. Three data sources were combined to construct the working sample: 1990 Census data, the 1994-95 PHDCN-CS, and the COSI data. Fifty-one ZIP code areas in Chicago and 12,672 elderly patients were studied. Community distress (HR = 1.04; 95% CI = (1.01, 1.07)) and anomie (HR = 1.26; 95% CI = (1.02, 1.54)) are found to be significantly and positively associated with a higher hazard of death. Moreover, community anomie contributes to the effect of community distress on post-hospitalisation mortality. The social, economic, physical and cultural environment in which people live appears to exert a significant impact on whether older people facing life-threatening illness live or die.

Acute Disease↗
PubMed2006

Identifying, recruiting, and retaining seriously-ill patients and their caregivers in longitudinal research.

BACKGROUND: In order to improve the state of science in palliative care, we must increase our ability to document the real-time experience of patients and families as they traverse the end of life. Yet, frequently, prospective measurement is impeded by difficulty with patient identification, recruitment, enrollment, and retention. The palliative care literature is replete with descriptions of studies unable to meet enrollment goals, and that as a result, do not have adequate power to test hypotheses or draw conclusions. OBJECTIVES: To review the literature describing difficulties associated with ascertainment, enrollment, and attrition. To outline the successful recruitment methods of a new longitudinal study of patients and their caregivers. DESIGN: A two-year longitudinal study of 240 patients with Stage IV cancer (breast, prostate, colorectal, lung), advanced congestive heart failure (CHF) LVEFB < 40 or advanced chronic obstructive pulmonary disease (COPD) pCO(2) > 46, and their caregivers, interviewed monthly for up to two years. Patients were identified using clinical and administrative databases from one geographic region. RESULTS: Representative and successful ascertainment was associated with use of clinical criteria and medical record review versus physician or other provider prognostication, use of recruitment letters from personal physician, recruitment letter content, brochure content, small monetary incentives, refined phone scripts, use of matched ethnicity interviewers, in-home and phone interview strategies, measure selection, patient and caregiver rapport, and on-going staff support (including grief and bereavement). CONCLUSIONS: Recruitment to prospective longitudinal studies at the end of life is difficult, but possible. The lessons learned from this study are applicable to future investigators conducting prospective research.

Caregivers↗
PubMed2005

Criterion validity of Medicare chemotherapy claims in Cancer and Leukemia Group B breast and lung cancer trial participants.

To determine the accuracy with which Medicare claims data measure chemotherapy use in elderly Medicare beneficiaries with cancer, we performed a criterion validation study. We compared gold-standard clinical trial data for 175 elderly cancer patients treated in two Cancer and Leukemia Group B (CALGB) breast and lung cancer trials (i.e., 45 from trial 9344 and 130 from trial 9730) with contemporaneous ambulatory and in-patient Medicare health insurance claims data from Centers for Medicare and Medicaid Services (CMS). The breast trial participants studied were those elderly enrolled between 1995 and 1997 and treated with doxorubicin and cyclophosphamide or this combination with paclitaxel. The lung trial participants studied were those elderly enrolled between 1998 and 2000 and treated with paclitaxel and carboplatin or paclitaxel alone. Comparing CALGB data with Medicare claims, we found the crude sensitivity for chemotherapy administration was 93% (95% confidence interval [CI] = 88% to 96%). Individual chemotherapy agents had similarly high sensitivities, ranging from 81% (95% CI = 70% to 89%) for carboplatin to 91% (95% CI = 79% to 98%) for cyclophosphamide. Agent-specific specificities were 100%. CMS data reliably captured repeat administration of chemotherapy to within one cycle. Administrative Medicare claims data appear to be a valid source of information for chemotherapy administered to elderly Medicare beneficiaries with cancer.

Aged↗
PubMed2005

Effect of specific aspects of community social environment on the mortality of individuals diagnosed with serious illness.

The purpose of this study was to examine the prospective and contextual effects of urban community environment on mortality among Medicare beneficiaries who were 67 years old or older in 1993, lived in the city of Chicago, and were hospitalized for one of 13 serious diseases. As expected, we found that advantageous socioeconomic context helps lower mortality risk among elderly patients over and above individual demographic and health background. We also found that collective efficacy was a health-enhancing social resource whereas criminal and violent activities in the community appeared to be deleterious. Inconsistent with our hypotheses, community social network density (measured by the size of social network and frequency of social interaction) was not protective but detrimental. Moreover, social support and the civic involvement of residents in the community do not seem to affect mortality. The complex relationship between community social environment and health found in this study may suggest that community-level social interventions based on social capital/social cohesion models are not likely to achieve fruitful results without concomitant effort in the economic and health care realm, at least in terms of influences on the health of older people once they are already ill.

Acute Disease↗
PubMed2005

Income inequality and weight status in US metropolitan areas.

Prior empirical studies have demonstrated an association between income inequality and general health endpoints such as mortality and self-rated health, and findings have been taken as support for the hypothesis that inequality is detrimental to individual health. Unhealthy weight statuses may function as an intermediary link between inequality and more general heath endpoints. Using individual-level data from the 1996-98 Behavioral Risk Factor Surveillance System, we examine the relationship between individual weight status and income inequality in US metropolitan areas. Income inequality is calculated with data from the 1990 US Census 5% Public Use Microsample. In analyses stratified by race-sex groups, we do not find a positive association between income inequality and weight outcomes such as body mass index, the odds of being overweight, and the odds of being obese. Among white women, however, we do find a statistically significant inverse association between inequality and each of these weight outcomes, despite adjustments for individual-level covariates, metropolitan-level covariates, and census region. We also find that greater inequality is associated with higher odds for trying to lose weight among white women, even adjusting for current weight status. Although our findings are suggestive of a contextual effect of metropolitan area income inequality, we do not find an increased risk for unhealthy weight outcomes, adding to recent debates surrounding this topic.

Adult↗
PubMed2005

Neighborhood effects on posthospitalization mortality: a population-based cohort study of the elderly in Chicago.

CONTEXT: Place of residence is associated with health outcomes. OBJECTIVE: To examine neighborhood effects on mortality after the onset of serious disease and to assess whether these effects vary for different sociodemographic or diagnostic subgroups. DESIGN, SETTING, PATIENTS: Our sample consists of a complete cohort of 10,557 elderly Medicare beneficiaries throughout the city of Chicago newly diagnosed and hospitalized for the first time with one of five common serious diseases in 1993 (stroke, myocardial infarction, congestive heart failure, hip fracture, and lung cancer) followed until 1999. Attributes of 51 zip code neighborhoods were obtained both from census data (1990) and from a comprehensive social survey of neighborhood residents (1994-1995). Cox proportional hazards models with robust standard errors were specified. MAIN OUTCOME MEASURE: Survival after hospitalization. RESULTS: People who lived in neighborhoods with higher socioeconomic status (SES) or with a better social environment had significantly longer survival after disease onset. We evaluated the differential impact of neighborhood attributes on survival depending on gender, race, and poverty using interaction terms. Only the interaction terms between neighborhood social-structural factors and individual poverty were significant, suggesting that neighborhood SES and social environment were especially helpful for people with higher income. Neighborhood attributes did not differ in their impact depending on the race or sex of the subjects. Analyses of cause-specific mortality showed that myocardial infarction was the primary force driving the associations between neighborhood attributes and mortality. CONCLUSIONS: Where people live matters with respect to posthospitalization mortality, but how neighborhoods affect this outcome depends on individual demographic and diagnostic characteristics. Myocardial infarction in particular may be a "neighborhood sensitive" condition. Individuals' health may depend not just on individuals' characteristics but also on their neighborhoods'.

Aged↗
PubMed2004

Measuring quality of life at the end of life: validation of the QUAL-E.

OBJECTIVES: To validate the QUAL-E, a new measure of quality of life at the end of life. METHODS: We conducted a cross-sectional study to assess the instrument's psychometric properties, including the QUAL-E's associations with existing measures, evaluation of robustness across diverse sample groups, and stability over time. The study was conducted at the VA and Duke University Medical Centers, Durham, North Carolina, in 248 patients with stage IV cancer, congestive heart failure with ejection fraction < or = 20%, chronic obstructive pulmonary disease with FEV1 < or = 1.0 1, or dialysis-dependent end stage renal disease. The main outcome measures included QUAL-E and five comparison measures: FACIT quality of life measure, Missoula-VITAS Quality of Life Index, FACIT-SP spirituality measures, Participatory Decision Making Scale (MOS), and Duke EPESE social support scales. RESULTS: QUAL-E analyses confirmed a four-domain structure (25 items): life completion (alpha = 0.80), symptoms impact (alpha = 0.87), relationship with health care provider (alpha = 0.71), and preparation for end of life (alpha = 0.68). Convergent and discriminant validity were demonstrated with multiple comparison measures. Test-retest reliability assessment showed stable scores over a 1-week period. SIGNIFICANCE OF RESULTS: The QUAL-E, a brief measure of quality of life at the end of life, demonstrates acceptable validity and reliability, is easy to administer, performs consistently across diverse demographic and disease groups, and is acceptable to seriously ill patients. It is offered as a new instrument to assist in the evaluation of the quality and effectiveness of interventions targeting improved care at the end of life.

Adult↗
PubMed2003

Complexities in prognostication in advanced cancer: "to help them live their lives the way they want to".

Predicting survival and disclosing the prediction to patients with advanced disease, particularly cancer, is among the most difficult tasks that physicians face. With the de-emphasis of prognosis in favor of diagnosis and therapeutics in the medical literature, physicians may have difficulty finding the survival information they need to make appropriate estimates of survival for patients who develop cancer. Quite separate from the challenge of estimating survival accurately, physicians may also find the process of disclosing the prognosis to their patients difficult. Using the vignette of a real patient with advanced cancer who far outlived her physician's prognostic estimate, we discuss clinical issues related to the science of prognosis in advanced cancer and the art of its disclosure.

Adenocarcinoma↗
PubMed2003

Favorable cardiac risk among elderly breast carcinoma survivors.

BACKGROUND: There are two reasons why women who survive breast carcinoma may be at a lower risk of developing coronary heart disease (CHD) compared with women without a history of breast carcinoma. First, estrogens may be etiologic in the development of breast carcinoma and protective of CHD. Second, a common therapy for breast carcinoma (tamoxifen) may be associated with cardiac protection. METHODS: In this population-level cohort study, the authors analyzed data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER)-Medicare program to study the cardiac risk of elderly female Medicare beneficiaries with and without a history of breast carcinoma. Using the SEER file, the authors identified elderly women survivors of Stage 0, I, or II breast carcinoma (n = 5980) diagnosed between the ages of 55 and 64. Using the Medicare 5% noncancer file, the authors also identified elderly women without a history of cancer (n = 23,165). They followed women from age 67 for up to 5 years for hospitalization for acute myocardial infarction (AMI) through a review of Medicare claims. The authors controlled the analyses for race, socioeconomic status, geographic location, cohort entry year, and medical comorbidity. RESULTS: The hazard of hospitalization for AMI for breast carcinoma survivors relative to comparison patients was 0.66 (95% confidence interval, 0.49-0.88). This apparent cardioprotective effect of breast carcinoma survivorship was stronger in breast carcinoma survivors with documented cardiac risk factors. CONCLUSIONS: Survivors of early-stage postmenopausal breast carcinoma are at a significantly lower risk of hospitalization for AMI than women who do not have a history of breast carcinoma. That survivors' risk varies with previous cardiac risk factors may be consistent with effects of selective estrogen receptor modulators. This phenomenon should be evaluated further with individual-level data containing information on patient cardiac risk factors and tamoxifen use to help clarify the mechanism behind the risk reduction.

Aged↗
PubMed2003

The health impact of health care on families: a matched cohort study of hospice use by decedents and mortality outcomes in surviving, widowed spouses.

Alternative ways of caring for seriously ill patients might have implications not only for patients' own outcomes, but also, indirectly, for the health outcomes of their family members. Clinical observation suggests that patients who die "good deaths" may impose less stress on their spouses. Consequently, we sought to assess whether hospice use by a decedent is associated with decreased risk of death in surviving, bereaved spouses. We conducted a matched retrospective cohort study involving a population-based sample of 195,553 elderly couples in the USA. A total of 30,838 couples where the decedent used hospice care were matched using the propensity score method to 30,838 couples where the decedent did not use hospice care. Our principal outcome of interest was the duration of survival of bereaved widow/ers. After adjustment for other measured variables, 5.4% of bereaved wives died by 18 months after the death of their husband when their deceased husband did not use hospice and 4.9% died when their deceased husband did use hospice, yielding an odds ratio (OR) of 0.92 (95% CI: 0.84-0.99) in favor of hospice use. Similarly, whereas 13.7% of bereaved husbands died by 18 months when their deceased wife did not use hospice, 13.2% died when their deceased wife did use hospice, yielding an OR of 0.95 (95% CI: 0.84-1.06) in favor of hospice use. Our findings suggest a possible beneficial impact of hospice--as a particularly supportive type of end-of-life care--on the spouses of patients who succumb to their disease. Hospice care might attenuate the ordinarily increased mortality associated with becoming widowed. This effect is present in both men and women, but it is statistically significant and possibly larger in bereaved wives. The size of this effect is comparable to the reductions in the risk of death seen in a variety of other modifiable risk factors in women. Health care may have positive, group-level health "externalities": it may affect the health not only of patients but also of patients' family members.

Aged↗
PubMed2003

Marriage, widowhood, and health-care use.

Despite suggestive evidence, there has been no adequately powered systematic study of the ways in which marital status influences health care consumption. Using a novel data set of 609016 newly diagnosed, seriously ill elderly individuals in the USA, and employing hierarchical linear models, we look at differences in the experience of hospitalization as a function of marital status. We find that the married consistently use higher quality hospitals and have shorter lengths of stay. On the other hand, the married and the widowed appear to receive similar quality care once they are in the hospital. Marital status thus has a substantial impact on the health care obtained by the elderly. We suggest that these patterns are most consistent with spouses exerting their benefits by functioning as higher-order decision-makers than as home health assistants.

Aged↗
PubMed2003

Self-perception of weight appropriateness in the United States.

UNLABELLED: BACKGROUND; The self-perception of weight appropriateness is an important component of eating and weight-loss behaviors. Self-perceived weight status, however, is not fully explained by objective weight status. OBJECTIVE: To examine the influence of sociodemographic factors on Americans' perceptions of their weight appropriateness, controlling for objective weight status. DESIGN: In the Third National Health and Nutrition Examination Survey, respondents were asked, "Do you consider yourself now to be overweight, underweight, or about the right weight?" Responses to this question were compared with how respondents (n=15,593) would be classified by medical standards given their body mass index (BMI). A proportional odds logistic regression model was used to assess the predictive effects of various sociodemographic factors on weight self-perception. RESULTS: Overall, 27.5% of women and 29.8% of men misclassified their own weight status by medical standards. Of particular note, 38.3% of normal weight women thought they were "overweight," while 32.8% of overweight men thought they were "about the right weight" or "underweight." Multivariate regression analysis revealed that, controlling for BMI, numerous factors-including gender, age, marital status, race, income, and education-were independently associated with the self-evaluation of weight status. CONCLUSIONS: The self-perceived appropriateness of weight status varies in highly predictable ways among population-level subgroups, likely reflecting differences in the normative evaluation of bodily weight standards. Such evaluations may assist in the explanation of discrepancies between clinical recommendations based on weight status and actual weight control behaviors, discrepancies that are socially patterned along some of the same subgroupings.

Adult↗