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1.
Ann Emerg Med ; 81(1): 14-19, 2023 01.
Article in English | MEDLINE | ID: mdl-36334954

ABSTRACT

STUDY OBJECTIVE: To describe characteristics and outcomes of coronavirus disease (COVID-19) patients with new supplemental oxygen requirements discharged from a large public urban emergency department (ED) with supplemental oxygen. METHODS: This observational case series describes the characteristics and outcomes of 360 consecutive COVID-19 patients with new supplemental oxygen requirements discharged from a large urban public ED between April 2020 and March 2021 with supplemental oxygen. Primary outcomes included 30-day survival and 30-day survival without unscheduled inpatient admission. Demographic and clinical data were collected through a structured chart review. RESULTS: Among 360 patients with COVID-19 discharged from the ED with supplemental oxygen, 30-day survival was 97.5% (95% confidence interval (CI) 95.3 to 98.9%; n=351), and 30-day survival without unscheduled admission was 81.1% (95% CI 76.7 to 85.0%; n=292). A sensitivity analysis incorporating worst-case-scenario for 12 patients without complete follow-up 30 days after index visit yields 30-day survival of 95.5% (95% CI 92.5 to 97.2%; n=343), and 30-day survival without unscheduled admission of 78.9% (95% CI 74.3 to 83.0%; n=284). Among study patients, 32.2% (n=116) had a nadir ED oxygen saturation of <90%, among these 30-day survival was 97.4% (95% CI 92.6 to 99.4%; n=113), and 30-day survival without unscheduled admission was 76.7% (95% CI 68.8 to 84.1%; n=89). CONCLUSION: COVID-19 patients with new supplemental oxygen requirements discharged from the ED had survival comparable to COVID-19 ED patients with mild exertional hypoxia treated with supplemental oxygen in other settings, and this held true when the analysis was restricted to patients with nadir ED index visit oxygen saturations <90%. Discharge of select COVID-19 patients with supplemental oxygen from the ED may provide a viable alternative to hospitalization, particularly when inpatient capacity is limited.


Subject(s)
COVID-19 , Patient Discharge , Humans , COVID-19/therapy , Hospitalization , Emergency Service, Hospital , Oxygen , Retrospective Studies
2.
AEM Educ Train ; 6(3): e10742, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35656534

ABSTRACT

Background: Emergency medicine (EM) physicians sometimes respond to critical events outside the emergency department. To prepare for these complex cases-typically called "rapid responses" (RRs)-EM residents receive simulation-based training involving four practice tasks and three exam tasks during a 1-day session. Cognitive load (CL) theory describes how humans function with limited working memories to perform complex tasks. RRs are expected to generate high levels of CL, but the profile of CL across providers and RR cases is not well understood. In this study, we analyzed resident's CL during RR training. We hypothesized variations in CL across individual and case and that exam cases would cause higher CLs than practice cases. Methods: Residents anonymously self-reported CL levels after each case using the Paas scale, a single-item, 9-point scale from "very, very low CL" to "very, very high CL." To examine case-based differences in CL, data were rescaled by individual residents. "High CL" was defined as a score of 9/9. Results: Among 18 residents participating, CLs ranged from 4 to 9, with median of 7 and interquartile range of 7-8. While many cases showed bell curve-like distributions of CLs, one case-a bleeding tracheostomy-showed a rightward skew reflecting higher levels of CL. No significant difference was found in CL between practice and exam cases. There were 20 reports (16.5%) of "high" CL with variation across residents (0/7 [0%] to 5/6 [83.3%] cases) and across cases (1/18 [5.6%) to 8/18 [44.4%]). Conclusions: The CL that EM residents experienced did show considerable interpersonal and intercase variation, but there was no significant difference between practice and exam cases. These results highlight several questions about how to optimally design future training, including how best to balance low and high CL training cases and which cases may require further training.

3.
J Am Coll Health ; 70(1): 18-21, 2022 01.
Article in English | MEDLINE | ID: mdl-32150523

ABSTRACT

Objective Opioid use and the risk of opioid overdose are growing public health concerns for college-aged adults. Naloxone can temporarily reverse opioid overdoses, but only if easily accessible. On most college campuses, "blue light" phones (BLPs)-call boxes topped with a blue light-offer visible access to emergency services. We hypothesized that BLPs would provide potential naloxone access points. Participants: A major university campus in Los Angeles, CA. Methods: BLP locations were obtained using Google Maps, and the area of campus within a set distance to each BLP calculated. To model effects of loss or diversion, we simulated the random loss of various BLPs. Results: Placing naloxone kits at the 59 BLP locations could provide access within 100 m to 91.5% of the campus. With loss of half of the BLPs, campus access remained above 70%. Conclusions: Naloxone at BLP locations could be accessed from almost all campus areas.


Subject(s)
Drug Overdose , Opiate Overdose , Adult , Drug Overdose/drug therapy , Humans , Naloxone/therapeutic use , Narcotic Antagonists/therapeutic use , Students , Universities , Young Adult
4.
West J Emerg Med ; 22(2): 234-243, 2021 Feb 08.
Article in English | MEDLINE | ID: mdl-33856306

ABSTRACT

INTRODUCTION: To describe the impact of COVID-19 on a large, urban emergency department (ED) in Los Angeles, California, we sought to estimate the effect of the novel coronavirus 2019 (COVID-19) and "safer-at-home" declaration on ED visits, patient demographics, and diagnosis-mix compared to prior years. METHODS: We used descriptive statistics to compare ED volume and rates of admission for patients presenting to the ED between January and early May of 2018, 2019, and 2020. RESULTS: Immediately after California's "safer-at-home" declaration, ED utilization dropped by 11,000 visits (37%) compared to the same nine weeks in prior years. The drop affected patients regardless of acuity, demographics, or diagnosis. Reductions were observed in the number of patients reporting symptoms often associated with COVID-19 and all other complaints. After the declaration, higher acuity, older, male, Black, uninsured or non-Medicaid, publicly insured, accounted for a disproportionate share of utilization. CONCLUSION: We show an abrupt, discontinuous impact of COVID-19 on ED utilization with a slow return as safer-at-home orders have lifted. It is imperative to determine how this reduction will impact patient outcomes, disease control, and the health of the community in the medium and long terms.


Subject(s)
COVID-19/epidemiology , Emergency Service, Hospital/statistics & numerical data , Adult , Age Distribution , Communicable Disease Control , Female , Humans , Los Angeles/epidemiology , Male , Medicaid/statistics & numerical data , Medicare/statistics & numerical data , Middle Aged , Pandemics , Patient Acuity , Patient Admission/statistics & numerical data , Racial Groups/statistics & numerical data , Retrospective Studies , Sex Distribution , United States/epidemiology , Urban Population
5.
West J Emerg Med ; 21(2): 291-294, 2020 Jan 27.
Article in English | MEDLINE | ID: mdl-31999248

ABSTRACT

INTRODUCTION: Detroit, Michigan, is among the leading United States cities for per-capita homicide and violent crime. Hospital- and community-based intervention programs could decrease the rate of violent-crime related injury but require a detailed understanding of the locations of violence in the community to be most effective. METHODS: We performed a retrospective geospatial analysis of all violent crimes reported within the city of Detroit from 2009-2015 comparing locations of crimes to locations of major hospitals. We calculated distances between violent crimes and trauma centers, and applied summary spatial statistics. RESULTS: Approximately 1.1 million crimes occurred in Detroit during the study period, including approximately 200,000 violent crimes. The distance between the majority of violent crimes and hospitals was less than five kilometers (3.1 miles). Among violent crimes, the closest hospital was an outlying Level II trauma center 60% of the time. CONCLUSION: Violent crimes in Detroit occur throughout the city, often closest to a Level II trauma center. Understanding geospatial components of violence relative to trauma center resources is important for effective implementation of hospital- and community-based interventions and targeted allocation of resources.


Subject(s)
Crime , Homicide , Trauma Centers , Violence/statistics & numerical data , Adult , Delivery of Health Care , Female , Health Services Accessibility , Humans , Male , Michigan , Retrospective Studies , Trauma Centers/statistics & numerical data , United States
7.
Am J Emerg Med ; 38(4): 794-798, 2020 04.
Article in English | MEDLINE | ID: mdl-31272755

ABSTRACT

OBJECTIVE: Identifying communities at high risk of stroke is an important step in improving systems of stroke care. Stroke is known to show spatial clustering at the state and county levels, but it is not known if clusters are present within city boundaries. METHODS: We performed a geospatial analysis of the prevalence of stroke within 500 major cities in the United States using the Centers for Disease Control and Prevention 500 Cities Project. For each city, we calculated the Moran's I statistic, which looks for evidence of spatial clustering, and used Monte Carlo simulation to assess for clustering significance. RESULTS: The mean overall crude prevalence of self-reported history of stroke at the city level was 2.8% (IQR 2.4-3.2%). Monte Carlo simulations of spatial patterns of stroke were successfully performed for 497 cities, of which 136 (27.3%) showed significant spatial clustering at the neighborhood level. All nine cities with more than one million inhabitants in 2010 showed significant spatial clustering. CONCLUSIONS: This is the first study to demonstrate that stroke shows clustering at the neighborhood level within many major cities in the United States and within all of the largest cities. Understanding where stroke clusters exist within cities can form the basis of optimizing emergency medical services deployment and improving systems of stroke care.


Subject(s)
Geographic Mapping , Residence Characteristics/statistics & numerical data , Stroke/epidemiology , Cities/epidemiology , Cities/statistics & numerical data , Cohort Studies , Cross-Sectional Studies , Humans , Monte Carlo Method , Prevalence , Retrospective Studies , Risk Factors , Socioeconomic Factors , United States/epidemiology
8.
Ann Emerg Med ; 75(3): 382-391, 2020 03.
Article in English | MEDLINE | ID: mdl-31515180

ABSTRACT

STUDY OBJECTIVE: The effect of urgent cares on local emergency department (ED) patient volumes is presently unknown. In this paper, we aimed to assess the change in low-acuity ED utilization at 2 academic medical centers in relation to patient proximity to an affiliated urgent care. METHODS: We created a geospatial database of ED visits occurring between April 2016 and March 2018 to 2 academic medical centers in an integrated health care system, geocoded by patient home address. We used logistic regression to characterize the relationship between the likelihood of patients visiting the ED for a low-acuity condition, based on ED discharge diagnosis, and urgent care center proximity, defined as living within 1 mile of an open urgent care center, for each of the academic medical centers in the system, adjusting for spatial, temporal, and patient factors. RESULTS: We identified a statistically significant reduction in the likelihood of ED visits for low-acuity conditions by patients living within 1 mile of an urgent care center at 1 of the 2 academic medical centers, with an adjusted odds ratio of 0.87 (95% confidence interval 0.78 to 0.98). There was, however, no statistically significant reduction at the other affiliated academic medical center. Further analysis showed a statistically significant temporal relationship between time since urgent care center opening and likelihood of a low-acuity ED visit, with approximately a 1% decrease in the odds of a low-acuity visit for every month that the proximal urgent care center was open (odds ratio 0.99; 95% confidence interval 0.985 to 0.997). CONCLUSION: Although further research is needed to assess the factors driving urgent care centers' variable influence on low-acuity ED use, these findings suggest that in similar settings urgent care center development may be an effective strategy for health systems hoping to decrease ED utilization for low-acuity conditions at academic medical centers.


Subject(s)
Academic Medical Centers/statistics & numerical data , Ambulatory Care Facilities/statistics & numerical data , Delivery of Health Care, Integrated/statistics & numerical data , Emergency Service, Hospital/statistics & numerical data , Patient Acceptance of Health Care/statistics & numerical data , Academic Medical Centers/organization & administration , Adult , Aged , Boston , Delivery of Health Care, Integrated/organization & administration , Emergency Service, Hospital/organization & administration , Female , Health Services Accessibility/organization & administration , Health Services Accessibility/statistics & numerical data , Humans , Male , Middle Aged , Spatial Analysis
9.
Am J Emerg Med ; 37(11): 2028-2034, 2019 11.
Article in English | MEDLINE | ID: mdl-30824273

ABSTRACT

BACKGROUND: Trauma is a major cause of death and disability in the United States, and significant disparities exist in access to care, especially in non-urban settings. From 2007 to 2017 New Mexico expanded its trauma system by focusing on building capacity at the hospital level. METHODS: We conducted a geospatial analysis at the census block level of access to a trauma center in New Mexico within 1 h by ground or air transportation for the years 2007 and 2017. We then examined the characteristics of the population with access to care. A multiple logistic regression model assessed for remaining disparities in access to trauma centers in 2017. RESULTS: The proportion of the population in New Mexico with access to a trauma center within 1 h increased from 73.8% in 2007 to 94.8% in 2017. The largest increases in access to trauma care within 1 h were found among American Indian/Alaska Native populations (AI/AN) (35.2%) and people living in suburban areas (62.9%). In 2017, the most rural communities (aOR 58.0), communities on an AI/AN reservation (aOR 25.6), communities with a high proportion of Hispanic/Latino persons (aOR 8.4), and a high proportion of elderly persons (aOR 3.2) were more likely to lack access to a trauma center within 1 h. CONCLUSION: The New Mexico trauma system expansion significantly increased access to trauma care within 1 h for most of New Mexico, but some notable disparities remain. Barriers persist for very rural parts of the state and for its sizable American Indian community.


Subject(s)
Health Services Accessibility/organization & administration , Healthcare Disparities/statistics & numerical data , Trauma Centers/organization & administration , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Cross-Sectional Studies , Female , Health Services Accessibility/statistics & numerical data , Healthcare Disparities/ethnology , Hispanic or Latino , Humans , Indians, North American , Infant , Infant, Newborn , Logistic Models , Male , Middle Aged , New Mexico , Retrospective Studies , Rural Health Services/organization & administration , Rural Health Services/supply & distribution , Trauma Centers/statistics & numerical data , Young Adult
10.
Am J Public Health ; 109(2): 270-272, 2019 02.
Article in English | MEDLINE | ID: mdl-30571296

ABSTRACT

We developed a nontargeted diabetes screening program in a rural Indian Health Service emergency department in Shiprock, New Mexico to measure the proportion of previously undiagnosed diabetes and prediabetes, and to assess glycemic control among patients with known disease. Of 924 patients screened in the emergency department between May and July 2017, 28.8% screened positive for previously undiagnosed diabetes or prediabetes; among patients with known disease, the median hemoglobin A1c was 8.2%. Of the newly identified patients, 54.9% attended follow-up.


Subject(s)
Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/epidemiology , Emergency Service, Hospital , Mass Screening/methods , Adult , Aged , Body Mass Index , Female , Glycated Hemoglobin/analysis , Humans , Indians, North American/statistics & numerical data , Male , Middle Aged , Public Health
11.
West J Emerg Med ; 19(4): 641-648, 2018 Jul.
Article in English | MEDLINE | ID: mdl-30013698

ABSTRACT

INTRODUCTION: The epidemic of opioid use disorder and opioid overdose carries extensive morbidity and mortality and necessitates a multi-pronged, community-level response. Bystander administration of the opioid overdose antidote naloxone is effective, but it is not universally available and requires consistent effort on the part of citizens to proactively carry naloxone. An alternate approach would be to position naloxone kits where they are most needed in a community, in a manner analogous to automated external defibrillators. We hypothesized that opioid overdoses would show geospatial clustering within a community, leading to potential target sites for such publicly deployed naloxone (PDN). METHODS: We performed a retrospective chart review of 700 emergency medical service (EMS) runs that involved opioid overdose or naloxone administration in Cambridge, Massachusetts, between October 16, 2016 and May 10, 2017. We used geospatial analysis to examine for clustering in general, and to identify specific clusters amenable to PDN sites. RESULTS: Opioid-related emergency medical services (EMS) runs in Cambridge, Massachusetts (MA), exhibit significant geospatial clustering, and we identified three clusters of opioid-related EMS runs in Cambridge, MA, with distinct characteristics. Models of PDN sites at these clusters show that approximately 40% of all opioid-related EMS runs in Cambridge, MA, would be accessible within 200 meters of PDN sites placed at cluster centroids. CONCLUSION: Identifying clusters of opioid-related EMS runs within a community may help to improve community coverage of naloxone, and strongly suggests that PDN could be a useful adjunct to bystander-administered naloxone in stemming the tide of opioid-related death.


Subject(s)
Analgesics, Opioid/toxicity , Drug Overdose/drug therapy , Emergency Medical Services , Geographic Information Systems/statistics & numerical data , Naloxone/therapeutic use , Narcotic Antagonists/therapeutic use , Opioid-Related Disorders/drug therapy , Drug Overdose/mortality , Humans , Massachusetts , Retrospective Studies
12.
Prehosp Emerg Care ; 22(6): 788-794, 2018.
Article in English | MEDLINE | ID: mdl-29723076

ABSTRACT

OBJECTIVE: Pre-stationing naloxone, a competitive antagonist that can reverse the effects of opioid overdose, in public spaces may expedite antidote delivery. Our study aimed to determine the feasibility of bystander-assisted overdose treatment using pre-stationed naloxone. METHODS: Convenience sample of bystanders in Cambridge, Massachusetts in April 2017. Subjects assisted a simulated patient described as unconscious. Subjects interacted with simulated EMS dispatch to locate a nearby box, unlock it, and administer naloxone. RESULTS: Fifty participants completed the simulation. Median time from simulated ambulance dispatch to naloxone administration was 189 seconds, and from arrival at patient side to administration 61 seconds. All but one participant (98.0%) correctly administered naloxone. Subjects' comfort with administration and willingness to provide medical care increased from before to after the trial. Comfort in administering naloxone varied significantly with level of previous training prior to, but not following, study participation. CONCLUSIONS: Bystanders are willing and able to access pre-stationed naloxone and administer it to a simulated patient in a public space. Public access naloxone stations may be a useful tool to reduce time to naloxone administration, particularly in areas where opioid overdoses are clustered.


Subject(s)
Analgesics, Opioid/administration & dosage , Drug Overdose/drug therapy , Health Services Accessibility , Naloxone/administration & dosage , Naloxone/therapeutic use , Narcotic Antagonists/administration & dosage , Narcotic Antagonists/therapeutic use , Public Facilities , Substance-Related Disorders/drug therapy , Adult , Aged , Emergency Medical Services , Feasibility Studies , Female , Helping Behavior , Humans , Male , Middle Aged , Young Adult
13.
PLoS One ; 12(3): e0175115, 2017.
Article in English | MEDLINE | ID: mdl-28362828

ABSTRACT

The opioid epidemic in the United States carries significant morbidity and mortality and requires a coordinated response among emergency providers, outpatient providers, public health departments, and communities. Anecdotally, providers across the spectrum of care at Massachusetts General Hospital (MGH) in Boston, MA have noticed that Charlestown, a community in northeast Boston, has been particularly impacted by the opioid epidemic and needs both emergency and longer-term resources. We hypothesized that geospatial analysis of the home addresses of patients presenting to the MGH emergency department (ED) with opioid-related emergencies might identify "hot spots" of opioid-related healthcare needs within Charlestown that could then be targeted for further investigation and resource deployment. Here, we present a geospatial analysis at the United States census tract level of the home addresses of all patients who presented to the MGH ED for opioid-related emergency visits between 7/1/2012 and 6/30/2015, including 191 visits from 100 addresses in Charlestown, MA. Among the six census tracts that comprise Charlestown, we find a 9.5-fold difference in opioid-related ED visits, with 45% of all opioid-related visits from Charlestown originating in tract 040401. The signal from this census tract remains strong after adjusting for population differences between census tracts, and while this tract is one of the higher utilizing census tracts in Charlestown of the MGH ED for all cause visits, it also has a 2.9-fold higher rate of opioid-related visits than the remainder of Charlestown. Identifying this hot spot of opioid-related emergency needs within Charlestown may help re-distribute existing resources efficiently, empower community and ED-based physicians to advocate for their patients, and serve as a catalyst for partnerships between MGH and local community groups. More broadly, this analysis demonstrates that EDs can use geospatial analysis to address the emergency and longer-term health needs of the communities they are designed to serve.


Subject(s)
Emergency Service, Hospital/statistics & numerical data , Epidemics/statistics & numerical data , Opioid-Related Disorders/epidemiology , Age Distribution , Female , Hospitals, General/statistics & numerical data , Humans , Male , Sex Distribution
15.
PLoS One ; 11(1): e0146859, 2016.
Article in English | MEDLINE | ID: mdl-26766306

ABSTRACT

INTRODUCTION: Although dehydration from diarrhea is a leading cause of morbidity and mortality in children under five, existing methods of assessing dehydration status in children have limited accuracy. OBJECTIVE: To assess the accuracy of point-of-care ultrasound measurement of the aorta-to-IVC ratio as a predictor of dehydration in children. METHODS: A prospective cohort study of children under five years with acute diarrhea was conducted in the rehydration unit of the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b). Ultrasound measurements of aorta-to-IVC ratio and dehydrated weight were obtained on patient arrival. Percent weight change was monitored during rehydration to classify children as having "some dehydration" with weight change 3-9% or "severe dehydration" with weight change > 9%. Logistic regression analysis and Receiver-Operator Characteristic (ROC) curves were used to evaluate the accuracy of aorta-to-IVC ratio as a predictor of dehydration severity. RESULTS: 850 children were enrolled, of which 771 were included in the final analysis. Aorta to IVC ratio was a significant predictor of the percent dehydration in children with acute diarrhea, with each 1-point increase in the aorta to IVC ratio predicting a 1.1% increase in the percent dehydration of the child. However, the area under the ROC curve (0.60), sensitivity (67%), and specificity (49%), for predicting severe dehydration were all poor. CONCLUSIONS: Point-of-care ultrasound of the aorta-to-IVC ratio was statistically associated with volume status, but was not accurate enough to be used as an independent screening tool for dehydration in children under five years presenting with acute diarrhea in a resource-limited setting.


Subject(s)
Dehydration/diagnostic imaging , Dehydration/etiology , Diarrhea/complications , Vena Cava, Inferior/diagnostic imaging , Acute Disease , Aorta/diagnostic imaging , Child, Preschool , Diarrhea/diagnosis , Female , Humans , Infant , Male , Point-of-Care Systems , Prognosis , Prospective Studies , ROC Curve , Reproducibility of Results , Risk Factors , Ultrasonography
18.
PLoS One ; 7(4): e34741, 2012.
Article in English | MEDLINE | ID: mdl-22558097

ABSTRACT

Serum bilirubin levels have been associated with polymorphisms in the UGT1A1 promoter in normal populations and in patients with hemolytic anemias, including sickle cell anemia. When hemolysis occurs circulating heme increases, leading to elevated bilirubin levels and an increased incidence of cholelithiasis. We performed the first genome-wide association study (GWAS) of bilirubin levels and cholelithiasis risk in a discovery cohort of 1,117 sickle cell anemia patients. We found 15 single nucleotide polymorphisms (SNPs) associated with total bilirubin levels at the genome-wide significance level (p value <5 × 10(-8)). SNPs in UGT1A1, UGT1A3, UGT1A6, UGT1A8 and UGT1A10, different isoforms within the UGT1A locus, were identified (most significant rs887829, p = 9.08 × 10(-25)). All of these associations were validated in 4 independent sets of sickle cell anemia patients. We tested the association of the 15 SNPs with cholelithiasis in the discovery cohort and found a significant association (most significant p value 1.15 × 10(-4)). These results confirm that the UGT1A region is the major regulator of bilirubin metabolism in African Americans with sickle cell anemia, similar to what is observed in other ethnicities.


Subject(s)
Anemia, Sickle Cell/complications , Anemia, Sickle Cell/genetics , Bilirubin/blood , Black or African American/genetics , Cholelithiasis/blood , Cholelithiasis/etiology , Glucuronosyltransferase/genetics , Anemia, Sickle Cell/blood , Bilirubin/genetics , Cohort Studies , Genome-Wide Association Study , Genotype , Humans , Inheritance Patterns/genetics , Isoenzymes/genetics , Polymorphism, Single Nucleotide/genetics , Principal Component Analysis , Risk Factors
19.
PLoS One ; 7(1): e29848, 2012.
Article in English | MEDLINE | ID: mdl-22279548

ABSTRACT

Like most complex phenotypes, exceptional longevity is thought to reflect a combined influence of environmental (e.g., lifestyle choices, where we live) and genetic factors. To explore the genetic contribution, we undertook a genome-wide association study of exceptional longevity in 801 centenarians (median age at death 104 years) and 914 genetically matched healthy controls. Using these data, we built a genetic model that includes 281 single nucleotide polymorphisms (SNPs) and discriminated between cases and controls of the discovery set with 89% sensitivity and specificity, and with 58% specificity and 60% sensitivity in an independent cohort of 341 controls and 253 genetically matched nonagenarians and centenarians (median age 100 years). Consistent with the hypothesis that the genetic contribution is largest with the oldest ages, the sensitivity of the model increased in the independent cohort with older and older ages (71% to classify subjects with an age at death>102 and 85% to classify subjects with an age at death>105). For further validation, we applied the model to an additional, unmatched 60 centenarians (median age 107 years) resulting in 78% sensitivity, and 2863 unmatched controls with 61% specificity. The 281 SNPs include the SNP rs2075650 in TOMM40/APOE that reached irrefutable genome wide significance (posterior probability of association = 1) and replicated in the independent cohort. Removal of this SNP from the model reduced the accuracy by only 1%. Further in-silico analysis suggests that 90% of centenarians can be grouped into clusters characterized by different "genetic signatures" of varying predictive values for exceptional longevity. The correlation between 3 signatures and 3 different life spans was replicated in the combined replication sets. The different signatures may help dissect this complex phenotype into sub-phenotypes of exceptional longevity.


Subject(s)
Aging/genetics , Genome, Human/genetics , Longevity/genetics , Polymorphism, Single Nucleotide , Aged , Aged, 80 and over , Alleles , Bayes Theorem , Cohort Studies , Female , Gene Frequency , Genetic Predisposition to Disease/genetics , Genotype , Humans , Male , Models, Genetic , Models, Statistical
20.
J Gerontol A Biol Sci Med Sci ; 67(4): 395-405, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22219514

ABSTRACT

We analyze the relationship between age of survival, morbidity, and disability among centenarians (age 100-104 years), semisupercentenarians (age 105-109 years), and supercentenarians (age 110-119 years). One hundred and four supercentenarians, 430 semisupercentenarians, 884 centenarians, 343 nonagenarians, and 436 controls were prospectively followed for an average of 3 years (range 0-13 years). The older the age group, generally, the later the onset of diseases, such as cancer, cardiovascular disease, dementia, and stroke, as well as of cognitive and functional decline. The hazard ratios for these individual diseases became progressively less with older and older age, and the relative period of time spent with disease was lower with increasing age group. We observed a progressive delay in the age of onset of physical and cognitive function impairment, age-related diseases, and overall morbidity with increasing age. As the limit of human life span was effectively approached with supercentenarians, compression of morbidity was generally observed.


Subject(s)
Age of Onset , Longevity , Morbidity , Aged, 80 and over , Cardiovascular Diseases/epidemiology , Cognition Disorders/epidemiology , Dementia/epidemiology , Female , Humans , Male , Neoplasms/epidemiology , Prevalence , Prospective Studies , Stroke/epidemiology
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