Phenomapping for the Identification of Hypertensive Patients with the Myocardial Substrate for Heart Failure with Preserved Ejection Fraction

We sought to evaluate whether unbiased machine learning of dense phenotypic data (“phenomapping”) could identify distinct hypertension subgroups that are associated with the myocardial substrate (i.e., abnormal cardiac mechanics) for heart failure with preserved ejection fraction (HFpEF). In the HyperGEN study, a population- and family-based study of hypertension, we studied 1273 hypertensive patients utilizing clinical, laboratory, and conventional echocardiographic phenotyping of the study participants. We used machine learning analysis of 47 continuous phenotypic variables to identify mutually exclusive groups constituting a novel classification of hypertension. The phenomapping analysis classified study participants into 2 distinct groups that differed markedly in clinical characteristics, cardiac structure/function, and indices of cardiac mechanics (e.g., phenogroup #2 had a decreased absolute longitudinal strain [12.8?±?4.1 vs. 14.6 ± 3.5%] even after adjustment for traditional comorbidities [p?<?0.001]). The 2 hypertension phenogroups may represent distinct subtypes that may benefit from targeted therapies for the prevention of HFpEF.     

Hospital management in the context of health sector reform: a planning model in Ethiopia

Through health sector reform in developing countries, Ministries of Health have sought to enhance health care through greater community governance and improved management effectiveness in their public hospitals. In this paper, we present a partnership-mentoring model for enhancing management capacity that has been piloted in Ethiopia and may be useful in other developing countries. The model included needs assessment and baseline evaluation using a hospital management indicator checklist, deployment of 24 Fellows (US and international hospital administrators) for 1 year to work as mentors with hospital management teams in 14 Ethiopian hospitals, continuing didactic and practical training in quality improvement methods for hospital management teams, and 24 management improvement projects to be completed during the year with plans for replication more broadly as appropriate. Surveys of Fellows and Ethiopian managers within the first quarter of onsite activity found high levels of trust in one another's abilities and intent to implement changes. The partnership-mentoring model promotes sustainability and may provide other countries with approaches for improving the quality of hospital care through improved hospital management. Copyright (c) 2007 John Wiley & Sons, Ltd.     

International Circumpolar Surveillance System for invasive pneumococcal disease, 1999-2005

The International Circumpolar Surveillance System is a population-based surveillance network for invasive bacterial disease in the Arctic. The 7-valent pneumococcal conjugate vaccine (PCV7) was introduced for routine infant vaccination in Alaska (2001), northern Canada (2002-2006), and Norway (2006). Data for invasive pneumococcal disease (IPD) were analyzed to identify clinical findings, disease rates, serotype distribution, and antimicrobial drug susceptibility; 11,244 IPD cases were reported. Pneumonia and bacteremia were common clinical findings. Rates of IPD among indigenous persons in Alaska and northern Canada were 43 and 38 cases per 100,000 population, respectively. Rates in children <2 years of age ranged from 21 to 153 cases per 100,000 population. In Alaska and northern Canada, IPD rates in children <2 years of age caused by PCV7 serotypes decreased by >80% after routine vaccination. IPD rates are high among indigenous persons and children in Arctic countries. After vaccine introduction, IPD caused by non-PCV7 serotypes increased in Alaska.     

Family interactions among African American prostate cancer survivors

Prostate cancer affects African Americans at a higher rate than any other ethnic group in the United States. Prostate cancer does not only affect the man with the disease but also affects those individuals who are closest to him, such as his family and friends. Open communication is valuable in coping with stressors that are affiliated with chronic illnesses. This article focuses on family and friend social support of men with prostate cancer. Data analysis revealed that support from family members and friends plays an important role in how men cope with their treatment and recovery from prostate cancer.     

Do STD clinic patients who consent to sexual health research differ from those who decline? Findings from a randomized controlled trial with implications for the generalization of research results

OBJECTIVES: This study determined whether patients from an STD clinic who agreed to participate in behavioral research are representative of the overall patient population. STUDY DESIGN: Patients attending an STD clinic (N = 2694) were invited to participate in sexual risk-reduction research. Those who accepted (consenters) were compared to those who declined (nonconsenters) on data obtained from the medical chart. RESULTS: Overall, 58% of eligible patients consented to participation. Logistic regression analyses indicated that consenting to participate was associated with female sex [odds ratio (OR) = 1.86], nonwhite race (OR = 2.16), having completed at least some college (OR = 1.70), being a returning patient (OR = 1.21), and having a greater number of sexual partners in the past 3 months (OR = 6.95) (all P's <0.05). CONCLUSIONS: Patients who agreed to participate had more education, were more familiar with the setting, and were more vulnerable to HIV/STD (as suggested by epidemiologic research). Efforts to enhance participation by an even greater percentage of patients might target these predictors of participation by enhancing risk awareness and providing preemptive reassurances regarding the research process and setting.     

Intravenous delivery of the plasma fraction of stored packed erythrocytes promotes pancreatic cancer growth in immunocompetent mice

BACKGROUND:

Perioperative blood transfusion in pancreatic cancer patients has been linked to decreased survival; however, a causal mechanism has not been determined. During the processing and storage of packed erythrocytes, biologically active molecules accumulated in the acellular plasma fraction; therefore, the authors hypothesized that the plasma fraction of stored packed erythrocytes promoted tumor progression.

METHODS:

Proliferation and migration of murine pancreatic cancer and control cells were determined in vitro in response to the plasma fraction from leukocyte and nonleukocyte‐reduced fresh versus stored packed erythrocytes. Last, an immunocompetent murine model was used to assess the effect of the plasma fraction of stored and processed packed erythrocytes on pancreatic cancer progression.

RESULTS:

Incubation of pancreatic cancer cells with the plasma fraction of packed erythrocytes increased proliferation and migration. Intravenous delivery of the acellular plasma fraction to mice with pancreatic cancer significantly increased the tumor weight in both leukocyte‐reduced and nonleukocyte‐reduced packed‐erythrocyte groups (P < .01), although tumor growth and morbidity were greatest in the nonleukocyte‐reduced group.

CONCLUSIONS:

The plasma fraction of stored packed erythrocytes promoted murine pancreatic cancer proliferation and migration in vitro and when administered intravenously, significantly augmented pancreatic cancer growth in immunocompetent mice. Cancer 2010. © 2010 American Cancer Society.     

Both t-Darpp and DARPP-32 can cause resistance to trastuzumab in breast cancer cells and are frequently expressed in primary breast cancers

The clinical use of trastuzumab (Herceptin™), a humanized antibody against the HER2 growth factor receptor, has improved survival in patients with breast tumors with ERBB2 amplification and/or over-expression. However, most patients with advanced ERBB2 amplified breast cancers whose tumors initially respond to trastuzumab develop resistance to the drug, leading to tumor progression. To identify factors responsible for acquired resistance to trastuzumab, gene expression profiling was performed on subclones of an ERBB2 amplified breast cancer cell line, BT474, which had acquired resistance to trastuzumab. The most overexpressed gene in these subclones was PPP1R1B, encoding the DARPP-32 phosphatase inhibitor. Western analysis revealed that only the truncated isoform of the DARPP-32 protein, t-Darpp, was overexpressed in the trastuzumab resistant cells. Using gene silencing experiments, we confirmed that t-Darpp over-expression was required for trastuzumab resistance in these cells. Furthermore, transfecting t-Darpp in parental BT-474 cells conferred resistance to trastuzumab, suggesting that t-Darpp expression was sufficient for trastuzumab resistance. We also found that t-Darpp over-expression was associated with Akt activation and that the T75 residue in t-Darpp was required for both Akt activation and trastuzumab resistance. Finally, we found that full-length DARPP-32 and t-Darpp are expressed in a majority of primary breast tumors. Over-expression of full-length DARPP-32 can also confer resistance to trastuzumab and, moreover, is associated with a poor prognostic value in breast cancers. Thus, t-Darpp and DARPP-32 expression are novel prognostic and predictive biomarkers in breast cancer.     

Preferences for active and aggressive intervention among patients with advanced cancer

Background  

Intrinsic to "Patient-Centered Care" is being respectful and responsive to individual patient preferences, expressed needs, and personal values. Establishing a patient's preferences for active and aggressive intervention is imperative and foundational to the development of advance care planning. With the increasing awareness and acceptance of palliative philosophies of care, patients with advanced cancer are increasingly transitioning from active and aggressive medical management (AAMM) to conservative palliative management (CPM).     

The Association Between A1C and Subclinical Cardiovascular Disease: The Multi-Ethnic Study of Atherosclerosis

OBJECTIVE

To test the hypothesis that A1C is associated with subclinical cardiovascular disease (CVD) in a population without evident diabetes, after adjusting for traditional CVD risk factors and BMI.

RESEARCH DESIGN AND METHODS

This was a cross-sectional study of 5,121 participants without clinically evident CVD or diabetes (fasting glucose ≥7.0 mmol/l or use of diabetes medication), aged 47–86 years, enrolled in the Multi-Ethnic Study of Atherosclerosis (MESA). Measurements included carotid intimal-medial wall thickness (CIMT) and coronary artery calcification (CAC). Results were adjusted for age, sex, ethnicity, smoking, systolic blood pressure, LDL cholesterol, HDL cholesterol, antihypertensive medication use, lipid-lowering medication use, and BMI.

RESULTS

Compared with those in the lowest quartile for A1C ([mean ± SD] 5.0 ± 0.2%), participants in the highest quartile (6.0 ± 0.3%) had higher adjusted mean values for common CIMT (0.85 vs. 0.87 mm, P = 0.003) and internal CIMT (1.01 vs. 1.08 mm, P = 0.003). A1C quartile was not associated with prevalence of CAC in the entire cohort (P = 0.27); however, the association was statistically significant in women (adjusted prevalence of CAC in lowest and highest A1C quartiles 37.5 vs. 43.0%, P = 0.01). Among those with some CAC, higher A1C quartile tended to be associated with higher CAC score, but the results were not statistically significant (adjusted P = 0.11).

CONCLUSIONS

In this multiethnic cohort, there were small, positive associations between A1C, common CIMT, and internal CIMT in the absence of clinically evident diabetes. An association between higher A1C and CAC prevalence was evident only in women.Higher level of A1C, a measurement of recent glycemia status, has been associated with clinical cardiovascular disease (CVD) in both the diabetic and nondiabetic population (1–3), but little information is available on the association between A1C and subclinical CVD in nondiabetic populations. Studies of subclinical CVD, including coronary artery calcification (CAC) and carotid intimal-medial wall thickness (CIMT), can provide complementary information to studies of clinical CVD outcomes by providing a more focused understanding of the factors that contribute to atherosclerosis, whereas studies of clinical CVD events are also influenced by factors related to plaque rupture and thrombosis. CAC and CIMT are associated with future risk of CVD events (4,5) and offer an opportunity to better understand the factors that contribute to the development and natural progression of early stage CVD.To date, the few studies that have examined the association between A1C and subclinical CVD in individuals without diabetes have shown mixed results. Sander et al. (6) found that A1C was associated with progression of common CIMT over 2 years, particularly when C-reactive protein (CRP) was also elevated. Doruk et al. (7) found no significant association between A1C and CIMT (mean of 12 common and internal CIMT measurements) in 78 elderly nondiabetic participants. Aihara et al. (8) showed that A1C was significantly associated with maximum plaque thickness (or CIMT if plaque was absent) in the internal or common carotid arteries in 306 Japanese participants; however, the association was not independent of diabetes status and was not described among nondiabetic participants. Temelkova-Kurktschiev et al. (9) showed that fasting glucose, glucose measured 2 h after an oral glucose load (2-h glucose), and A1C were each associated with common CIMT in 582 German participants without clinically diagnosed diabetes after adjusting for age and sex, but 30% of these participants had undiagnosed diabetes.To our knowledge, there are no published studies examining the association between A1C and CAC in participants without clinically evident diabetes and no large studies of A1C and CIMT in minority ethnic populations. The purpose of this study was to test the hypothesis that A1C within the range observed in subjects without clinically evident diabetes is associated with subclinical CVD after accounting for traditional CVD risk factors and that this association persists after further adjustment for BMI. Secondary aims of this study were to determine whether the association between A1C and subclinical CVD varied by sex or race/ethnicity and whether results were explained by differences in other nontraditional CVD risk factors (triglycerides, CRP, intentional exercise, and albuminuria).