UMCCTS Supported Publications

Resistance is futile: the bacteriocin model for addressing the antibiotic resistance challenge

Margaret A. Riley et al. — Mon, 13 May 2013 08:11:29 PDT

Pathogenic bacteria resistant to many or all antibiotics already exist. With the decline in microbiological research at pharmaceutical companies, the high rate at which resistance has evolved and spread has demanded a novel approach to addressing this critical human health issue. In the present paper, we propose a new paradigm in antibiotic discovery and development, one that applies ecological and evolutionary theory to design antimicrobial drugs that are more difficult and/or more costly to resist. In essence, we propose to simply adopt the strategies invented and applied by bacteria for hundreds of millions of years. Our research focuses on bacteriocins, powerful biological weapons, and their use as alternative therapeutics in human health.

Six-month mortality and cardiac catheterization in non-ST-segment elevation myocardial infarction patients with anemia

Wen-Chih Wu et al. — Mon, 14 May 2012 08:42:17 PDT

BACKGROUND: It is unknown how anemia influences the invasive management of patients with non-ST-segment elevation myocardial infarction (NSTEMI) and associated mortality. We investigated whether receipt of cardiac catheterization relates to 6-month death rates among patients with different severity of anemia.

METHODS: We used data from the population-based Worcester Heart Attack Study, which included 2634 patients hospitalized with confirmed NSTEMI, from three percutaneous coronary intervention-capable medical centers in the Worcester (Massachusetts, U.S.A.) metropolitan area, during five biennial periods between 1997 and 2005. Severity of anemia was categorized using admission hematocrit levels: less than or equal to 30.0% (moderate-to-severe anemia), 30.1-39.0% (mild anemia), and more than 39.0% (no anemia). Propensity matching and conditional logistic regression adjusting for hospital use of aspirin, heparin, and plavix compared 6-month postadmission all-cause mortality rates in relation to cardiac catheterization during NSTEMI hospitalization.

RESULTS: Compared with patients without anemia, patients with anemia were less likely to undergo cardiac catheterization {adjusted odds ratio (AOR) 0.79 [95% confidence interval (CI): 0.67-0.95] for mild anemia and 0.45 (95% CI: 0.42-0.49) for moderate-to-severe anemia}. After propensity matching, cardiac catheterization was associated with lower 6-month death rates only in patients without anemia [AOR 0.26 (95% CI: 0.09-0.79)] but not in patients with mild anemia [AOR 0.55 (95% CI: 0.25-1.23)]. The small number of patients rendered data inconclusive for patients with moderate-to-severe anemia.

CONCLUSION: Anemia at the time of hospitalization for NSTEMI was associated with lower utilization of cardiac catheterization. However, cardiac catheterization use was associated with a decreased risk of dying at 6 months after hospital admission only in patients without anemia.

Weight and mortality following heart failure hospitalization among diabetic patients

Molly E. Waring et al. — Mon, 14 May 2012 08:42:15 PDT

BACKGROUND: Type 2 diabetes is an important risk factor for heart failure and is common among patients with heart failure. The impact of weight on prognosis after hospitalization for acute heart failure among patients with diabetes is unknown. The objective of this study was to examine all-cause mortality in relation to weight status among patients with type 2 diabetes hospitalized for decompensated heart failure.

METHODS: The Worcester Heart Failure Study included adults admitted with acute heart failure to all metropolitan Worcester medical centers in 1995 and 2000. The weight status of 1644 patients with diabetes (history of type 2 diabetes in medical record or admission serum glucose >/=200 mg/dL) was categorized using body mass index calculated from height and weight at admission. Survival status was ascertained at 1 and 5 years after hospital admission. RESULTS: Sixty-five percent of patients were overweight or obese and 3% were underweight. Underweight patients had 50% higher odds of all-cause mortality within 5 years of hospitalization for acute heart failure than normal weight patients. Class I and II obesity were associated with 20% and 40% lower odds of dying. Overweight and Class III obesity were not associated with mortality. Results were similar for mortality within 1 year of hospitalization for acute heart failure.

CONCLUSIONS: The mechanisms underlying the association between weight status and mortality are not fully understood. Additional research is needed to explore the effects of body composition, recent weight changes, and prognosis after hospitalization for heart failure among patients with diabetes.

Professional values and reported behaviours of doctors in the USA and UK: quantitative survey

Martin Roland et al. — Mon, 14 May 2012 08:42:13 PDT

BACKGROUND: The authors aimed to determine US and UK doctors' professional values and reported behaviours, and the extent to which these vary with the context of care.

METHOD: 1891 US and 1078 UK doctors completed the survey (64.4% and 40.3% response rate respectively). Multivariate logistic regression was used to compare responses to identical questions in the two surveys.

RESULTS: UK doctors were more likely to have developed practice guidelines (82.8% UK vs 49.6% US, p<0.001) and to have taken part in a formal medical error-reduction programme (70.9% UK vs 55.7% US, p<0.001). US doctors were more likely to agree about the need for periodic recertification (completely agree 23.4% UK vs 53.9% US, p<0.001). Nearly a fifth of doctors had direct experience of an impaired or incompetent colleague in the previous 3 years. Where the doctor had not reported the colleague to relevant authorities, reasons included thinking that someone else was taking care of the problem, believing that nothing would happen as a result, or fear of retribution. UK doctors were more likely than US doctors to agree that significant medical errors should always be disclosed to patients. More US doctors reported that they had not disclosed an error to a patient because they were afraid of being sued.

DISCUSSION: The context of care may influence both how professional values are expressed and the extent to which behaviours are in line with stated values. Doctors have an important responsibility to develop their healthcare systems in ways which will support good professional behaviour.

Extensive genome-wide variability of human cytomegalovirus in congenitally infected infants

Nicholas Renzette et al. — Mon, 14 May 2012 08:42:11 PDT

Research has shown that RNA virus populations are highly variable, most likely due to low fidelity replication of RNA genomes. It is generally assumed that populations of DNA viruses will be less complex and show reduced variability when compared to RNA viruses. Here, we describe the use of high throughput sequencing for a genome wide study of viral populations from urine samples of neonates with congenital human cytomegalovirus (HCMV) infections. We show that HCMV intrahost genomic variability, both at the nucleotide and amino acid level, is comparable to many RNA viruses, including HIV. Within intrahost populations, we find evidence of selective sweeps that may have resulted from immune-mediated mechanisms. Similarly, genome wide, population genetic analyses suggest that positive selection has contributed to the divergence of the HCMV species from its most recent ancestor. These data provide evidence that HCMV, a virus with a large dsDNA genome, exists as a complex mixture of genome types in humans and offer insights into the evolution of the virus.

Electronic health records in small physician practices: availability, use, and perceived benefits

Sowmya R. Rao et al. — Mon, 14 May 2012 08:42:08 PDT

OBJECTIVE: To examine variation in the adoption of electronic health record (EHR) functionalities and their use patterns, barriers to adoption, and perceived benefits by physician practice size.

DESIGN: Mailed survey of a nationally representative random sample of practicing physicians identified from the Physician Masterfile of the American Medical Association. Measurements We measured, stratified by practice size: (1) availability of EHR functionalities, (2) functionality use, (3) barriers to the adoption and use of EHR, and (4) impact of the EHR on the practice and quality of patient care.

RESULTS: With a response rate of 62%, we found that < 2% of physicians in solo or two-physician (small) practices reported a fully functional EHR and 5% reported a basic EHR compared with 13% of physicians from 11+ group (largest group) practices with a fully functional system and 26% with a basic system. Between groups, a 21-46% difference in specific functionalities available was reported. Among adopters there were moderate to large differences in the use of the EHR systems. Financial barriers were more likely to be reported by smaller practices, along with concerns about future obsolescence. These differences were sizable (13-16%) and statistically significant (p < 0.001). All adopters reported similar benefits. Limitations Although we have adjusted for response bias, influences may still exist.

CONCLUSION: Our study found that physicians in small practices have lower levels of EHR adoption and that these providers were less likely to use these systems. Ensuring that unique barriers are addressed will be critical to the widespread meaningful use of EHR systems among small practices.

Venous thromboembolism in patients with reduced estimated GFR: a population-based perspective

Amisha M. Parikh et al. — Mon, 14 May 2012 08:42:06 PDT

BACKGROUND: An increased frequency of venous thromboembolism (VTE) has been shown in patients with decreased kidney function measured by decreased estimated glomerular filtration rate (eGFR). However, present practices with respect to VTE prevention and management in patients with decreased eGFR in general population settings are uncertain.

STUDY DESIGN: Observational study.

SETTING and PARTICIPANTS: Community investigation of 1,509 metropolitan Worcester, MA, residents with a validated VTE in 1999, 2001, and 2003 with further follow-up for up to 3 years.

PREDICTOR: Patients with VTE classified further according to eGFR on presentation: /=90 mL/min/1.73 m(2) (reference group).

OUTCOMES: Recurrent VTE, major bleeding episodes, and all-cause mortality.

MEASUREMENTS: Demographic and clinical characteristics, treatment practices, and study outcomes were extracted from patients' hospital and outpatient medical records; eGFR was estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.

RESULTS: Patients with VTE with eGFR /min/1.73 m(2) were at increased risk of recurrent VTE (HR, 1.83; 95% CI, 1.03-3.25), major bleeding episodes (HR, 2.30; 95% CI, 1.28-4.16), and all-cause mortality (HR, 1.70; 95% CI, 1.12-2.57) during a 3-year follow-up. Patients with decreased eGFR also presented with more comorbid conditions and were less likely to be discharged on any form of anticoagulant therapy (72.6%, 81.0%, 82.1%, and 87.3% for eGFR /=90 mL/min/1.73 m(2), respectively; P < 0.001).

LIMITATIONS: Decreased eGFR status is presumed based on creatinine values on clinical presentation. The impact of drug dosage, timing, type of anticoagulant therapy, and medication adherence on study outcomes could not be evaluated.

CONCLUSIONS: Severe decreases in eGFR are associated with increased risk of long-term recurrent VTE, bleeding, and total mortality in patients with VTE. A greater frequency of serious comorbid conditions, difficulties implementing available management strategies, and suboptimal VTE prophylaxis during hospital admissions likely contributed to our findings. All rights reserved.

Thirty-year (1975 to 2005) trends in the incidence rates, clinical features, treatment practices, and short-term outcomes of patients [less than] 55 years of age hospitalized with an initial acute myocardial infarction

David D. McManus et al. — Mon, 14 May 2012 08:42:04 PDT

Sparse data are available describing recent trends in the magnitude, clinical features, treatment practices, and outcomes of comparatively young adults hospitalized with acute myocardial infarction (AMI). The objectives of this population-based study were to describe 3 decade-long trends (1975 to 2005) in these end points in adults 1,703 residents of the Worcester (Massachusetts) metropolitan area 25 to 54 years of age who were hospitalized with initial AMIs at all central Massachusetts medical centers during 15 annual periods from 1975 through 2005. Overall hospital incidence rate (per 100,000 residents) of initial AMI in our study population was 66 (95% confidence interval 63 to 69) and incidence rates of AMI decreased inconsistently over time. Patients hospitalized during the most recent study years were more likely to have important cardiovascular risk factors and co-morbidities present but were less likely to have developed heart failure during their index hospitalization. In-hospital and 30-day death rates decreased by approximately 50% (p = 0.04) during the years under study concomitant with increasing use of effective cardiac therapies. In conclusion, the results of this community-wide investigation provide insights into the magnitude, changing characteristics, and short-term outcomes of comparatively young patients hospitalized with a first AMI. Decreasing odds of developing or dying from an initial AMI during the 30 years under study likely reflect increased primary and secondary prevention and treatment efforts.

Genetic variation in stearoyl-CoA desaturase 1 is associated with metabolic syndrome prevalence in Costa Rican adults

Jian Gong et al. — Mon, 14 May 2012 08:42:02 PDT

Stearoyl-CoA desaturase 1 (SCD1) activity, a key regulator of lipid metabolism, may be associated with the development of metabolic syndrome (MetS). We examined the association of genetic variation in the SCD1 gene with the occurrence of MetS and its five components in a population of Costa Rican adults (n = 2152; mean age, 58 y; range, 18-86 y). Associations of tag single nucleotide polymorphisms (tagSNP) of the SCD1 gene with prevalence of MetS and its five components were analyzed by use of log-Poisson models with robust variance estimates and linear regression models, respectively. The likelihood ratio was used to test potential gene-fatty acid interactive effects with adipose tissue alpha-linolenic acid. One tagSNP (rs1502593) was significantly associated with an increased prevalence of MetS in the total study sample. Compared with the common homozygous CC genotype, the CT and TT genotypes for rs1502593 were associated with higher prevalence ratios (PR) of MetS for CT vs. CC: [PR = 1.22 (95% CI = 1.03, 1.44)] and for TT vs. CC [PR = 1.24 (95% CI = 1.01, 1.52)]. Among women, we observed borderline positive associations between systolic blood pressure and fasting blood sugar levels and rs1502593 (P = 0.05 and 0.06). Compared to the common haplotype (frequency >/= 5%) with no minor alleles of SCD1 tagSNP, the other two observed common haplotypes carrying the rs1502593 minor allele were significantly associated with elevated prevalence of MetS. No gene-fatty acid interactive effects were observed. Our results suggest that genetic variation in the SCD1 gene may play a role in the development of MetS.

A prospective study of the rate of progression in compensated, histologically advanced chronic hepatitis C

Jules L. Dienstag et al. — Mon, 14 May 2012 08:42:00 PDT

The incidence of liver disease progression among subjects with histologically advanced but compensated chronic hepatitis C is incomplete. The Hepatitis C Antiviral Long-term Treatment against Cirrhosis Trial was a randomized study of 3.5 years of maintenance peginterferon treatment on liver disease progression among patients who had not cleared virus on peginterferon and ribavirin therapy. Patients were followed subsequently off therapy. Because maintenance peginterferon treatment did not alter liver disease progression, we analyzed treated and control patients together. Among 1,050 subjects (60% advanced fibrosis, 40% cirrhosis), we determined the rate of progression to cirrhosis over 4 years and of clinical outcomes over 8 years. Among patients with fibrosis, the incidence of cirrhosis was 9.9% per year. Six hundred seventy-nine clinical outcomes occurred among 329 subjects. Initial clinical outcomes occurred more frequently among subjects with cirrhosis (7.5% per year) than subjects with fibrosis (3.3% per year) (P/=7 was the most common first outcome, followed by hepatocellular carcinoma. Following occurrence of a CTP score>/=7, the rate of subsequent events increased to 12.9% per year, including a death rate of 10% per year. Age and sex did not influence outcome rates. Baseline platelet count was a strong predictor of all clinical outcomes. During the 8 years of follow-up, death or liver transplantation occurred among 12.2% of patients with advanced fibrosis and 31.5% of those with cirrhosis.

CONCLUSION: Among patients with advanced hepatitis C who failed peginterferon and ribavirin therapy, the rate of liver-related outcomes, including death and liver transplantation, is high, especially once the CTP score reaches at least 7.

Assessment of differential item functioning in the experiences of discrimination index: the Coronary Artery Risk Development in Young Adults (CARDIA) Study

Timothy J. Cunningham et al. — Mon, 14 May 2012 08:41:57 PDT

The psychometric properties of instruments used to measure self-reported experiences of discrimination in epidemiologic studies are rarely assessed, especially regarding construct validity. The authors used 2000-2001 data from the Coronary Artery Risk Development in Young Adults (CARDIA) Study to examine differential item functioning (DIF) in 2 versions of the Experiences of Discrimination (EOD) Index, an index measuring self-reported experiences of racial/ethnic and gender discrimination. DIF may confound interpretation of subgroup differences. Large DIF was observed for 2 of 7 racial/ethnic discrimination items: White participants reported more racial/ethnic discrimination for the "at school" item, and black participants reported more racial/ethnic discrimination for the "getting housing" item. The large DIF by race/ethnicity in the index for racial/ethnic discrimination probably reflects item impact and is the result of valid group differences between blacks and whites regarding their respective experiences of discrimination. The authors also observed large DIF by race/ethnicity for 3 of 7 gender discrimination items. This is more likely to have been due to item bias. Users of the EOD Index must consider the advantages and disadvantages of DIF adjustment (omitting items, constructing separate measures, and retaining items). The EOD Index has substantial usefulness as an instrument that can assess self-reported experiences of discrimination.

Fast food restaurants and food stores: longitudinal associations with diet in young to middle-aged adults: the CARDIA study

Janne Boone-Heinonen et al. — Mon, 14 May 2012 08:41:55 PDT

BACKGROUND: A growing body of cross-sectional, small-sample research has led to policy strategies to reduce food deserts--neighborhoods with little or no access to healthy foods--by limiting fast food restaurants and small food stores and increasing access to supermarkets in low-income neighborhoods.

METHODS: We used 15 years of longitudinal data from the Coronary Artery Risk Development in Young Adults (CARDIA) study, a cohort of US young adults (aged 18-30 years at baseline) (n = 5115), with linked time-varying geographic information system-derived food resource measures. Using repeated measures from 4 examination periods (n = 15,854 person-examination observations) and conditional regression (conditioned on the individual), we modeled fast food consumption, diet quality, and adherence to fruit and vegetable recommendations as a function of fast food chain, supermarket, or grocery store availability (counts per population) within less than 1.00 km, 1.00 to 2.99 km, 3.00 to 4.99 km, and 5.00 to 8.05 km of respondents' homes. Models were sex stratified, controlled for individual sociodemographic characteristics and neighborhood poverty, and tested for interaction by individual-level income.

RESULTS: Fast food consumption was related to fast food availability among low-income respondents, particularly within 1.00 to 2.99 km of home among men (coefficient, 0.34; 95% confidence interval, 0.16-0.51). Greater supermarket availability was generally unrelated to diet quality and fruit and vegetable intake, and relationships between grocery store availability and diet outcomes were mixed.

CONCLUSION: Our findings provide some evidence for zoning restrictions on fast food restaurants within 3 km of low-income residents but suggest that increased access to food stores may require complementary or alternative strategies to promote dietary behavior change.

Food insufficiency and health services utilization in a national sample of homeless adults

Travis P. Baggett et al. — Mon, 14 May 2012 08:41:53 PDT

BACKGROUND: Homeless people have high rates of hospitalization and emergency department (ED) use. Obtaining adequate food is a common concern among homeless people and may influence health care utilization.

OBJECTIVE: We tested the hypothesis that food insufficiency is related to higher rates of hospitalization and ED use in a national sample of homeless adults.

DESIGN: We analyzed data from the 2003 Health Care for the Homeless (HCH) User Survey.

PARTICIPANTS: Participants were 966 adults surveyed at 79 HCH clinic sites throughout the US. The study sample was representative of over 436,000 HCH clinic users nationally.

MEASURES: We determined the prevalence and characteristics of food insufficiency among respondents. Using multivariable logistic regression, we examined the association between food insufficiency and four past-year acute health services utilization outcomes: (1) hospitalization for any reason, (2) psychiatric hospitalization, (3) any ED use, and (4) high ED use (>/= 4 visits).

RESULTS: Overall, 25% of respondents reported food insufficiency. Among them, 68% went a whole day without eating in the past month. Chronically homeless (p = 0.01) and traumatically victimized (p = 0.001) respondents were more likely to be food insufficient. In multivariable analyses, food insufficiency was associated with significantly greater odds of hospitalization for any reason (AOR 1.59, 95% CI 1.07, 2.36), psychiatric hospitalization (AOR 3.12, 95% CI 1.73, 5.62), and high ED utilization (AOR 2.83, 95% CI 1.32, 6.08).

CONCLUSIONS: One-fourth of homeless adults in this national survey were food insufficient, and this was associated with increased odds of acute health services utilization. Addressing the adverse health services utilization patterns of homeless adults will require attention to the social circumstances that may contribute to this issue.