BCR-ABL tyrosine kinase inhibitors (TKIs) are effective in controlling Philadelphia-positive (Ph+) chronic myeloid leukemia (CML) are unlikely to cure the disease because TKIs are unable to eradicate leukemia stem cells (LSCs) responsible for the disease relapse even after tyrosine kinase inhibition. In addition, the TKI resistance of LSCs is not associated with the BCR-ABL kinase domain mutations. These observations indicate that TKI-insensitive LSCs and TKI-sensitive leukemic progenitor cells are biologically different, which leads us to believe that LSCs and more differentiated leukemic cells have different genetic mechanisms. Further study of LSCs to identify the novel gene signatures and mechanisms that control the function and molecular phenotype of LSCs is critical. In this mini-review, we will discuss our current understanding of the biology of LSCs and novel genes that could serve as a molecular signature of LSCs in CML. These novel genes could also serve as potential targets for eradicating LSCs in CML.
Social support and smoking abstinence among incarcerated adults in the United States: a longitudinal study
BACKGROUND: In the United States, tobacco use among prisoners is nearly three times that of the general population. While many American prisons and jails are now tobacco-free, nearly all inmates return to smoking as soon as they are released back into the community.
METHODS: To better understand the role that personal relationships may play in enabling return to smoking, we enrolled former-smokers who were inmates in a tobacco-free prison. Baseline assessments were conducted six weeks prior to inmates' scheduled release and included measures of smoking prior to incarceration, motivation, confidence and plans for remaining quit after release. We also assessed global social support (ISEL) and a measure of social support specific to quitting smoking (SSQ). Smoking status was assessed three weeks after prison release and included 7-day point-prevalence abstinence validated by urine cotinine, days to first cigarette and smoking rate.
RESULTS: A diverse sample comprised of 35% women, 20% Hispanic, and 29% racial minorities (average age 35.5 years) provided baseline data (n = 247). Over 90% of participants provided follow up data at 3-weeks post-release. Prior to incarceration participants had smoked an average of 21.5 (SD = 11.7) cigarettes per day. Only 29.2% had definite plans to remain smoking-abstinent after release. Approximately half of all participants reported that "most" or "all" of their family (42.2%) and friends (68%) smoked, and 58.8% reported their spouse or romantic partner smoked.SSQ scores were not significantly predictive of smoking outcomes at three weeks, however, social support from family and friends were each significantly and positively correlated with motivation, confidence, and plans for remaining abstinent (all p values <0.05). These smoking-related attitudinal variables were significantly predictive of smoking outcomes (all p values <0.01). General social support (ISEL) was not associated with smoking-related attitudinal variables or smoking outcomes.
CONCLUSIONS: Inmates of smoke-free prisons have a head-start on being smoke-free for life. They have been abstinent well past the duration of nicotine withdrawal and have great financial incentive not to begin smoking again. However, this advantage may be offset by a lack of non-smoking role models among their family and friends, and perceived lack of support for remaining smoke-free.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01684995.
BACKGROUND: Amyotrophic lateral sclerosis (ALS)-linked fused in sarcoma/translocated in liposarcoma (FUS/TLS or FUS) is concentrated within cytoplasmic stress granules under conditions of induced stress. Since only the mutants, but not the endogenous wild-type FUS, are associated with stress granules under most of the stress conditions reported to date, the relationship between FUS and stress granules represents a mutant-specific phenotype and thus may be of significance in mutant-induced pathogenesis. While the association of mutant-FUS with stress granules is well established, the effect of the mutant protein on stress granules has not been examined. Here we investigated the effect of mutant-FUS on stress granule formation and dynamics under conditions of oxidative stress.
RESULTS: We found that expression of mutant-FUS delays the assembly of stress granules. However, once stress granules containing mutant-FUS are formed, they are more dynamic, larger and more abundant compared to stress granules lacking FUS. Once stress is removed, stress granules disassemble more rapidly in cells expressing mutant-FUS. These effects directly correlate with the degree of mutant-FUS cytoplasmic localization, which is induced by mutations in the nuclear localization signal of the protein. We also determine that the RGG domains within FUS play a key role in its association to stress granules. While there has been speculation that arginine methylation within these RGG domains modulates the incorporation of FUS into stress granules, our results demonstrate that this post-translational modification is not involved.
CONCLUSIONS: Our results indicate that mutant-FUS alters the dynamic properties of stress granules, which is consistent with a gain-of-toxic mechanism for mutant-FUS in stress granule assembly and cellular stress response.
Congenital heart defects often result from improper differentiation of cardiac progenitor cells. Although transcription factors involved in cardiac progenitor cell differentiation have been described, the associated chromatin modifiers in this process remain largely unknown. Here we show that mouse embryos lacking the chromatin-modifying enzyme histone deacetylase 3 (Hdac3) in cardiac progenitor cells exhibit precocious cardiomyocyte differentiation, severe cardiac developmental defects, upregulation of Tbx5 target genes and embryonic lethality. Hdac3 physically interacts with Tbx5 and modulates its acetylation to repress Tbx5-dependent activation of cardiomyocyte lineage-specific genes. These findings reveal that Hdac3 plays a critical role in cardiac progenitor cells to regulate early cardiogenesis.
OBJECTIVES: To explore patients' and family members' views on communication during cancer care and to identify those aspects of clinician-patient communication which were most important to patients and family members.
METHODS: We conducted a secondary data analysis of qualitative data from 137 patients with cancer and family members of patients with cancer. We used a modified version of the constant comparative method and coding paradigm of grounded theory.
RESULTS: Patients want sensitive, caring clinicians who provide information that they need, when they need it, in a way that they can understand; who listen and respond to questions and concerns, and who attempt to understand the patient's experience. Effective information exchange and a positive interpersonal relationship with the clinician were of fundamental importance to patients and family members. These were interrelated; for instance, failure to provide information a patient needed could damage the relationship, whereas excellent listening could foster the relationship. Information exchange and relationship were also integral to decision-making, managing uncertainty, responding to emotions, and self-management. Clinicians who were responsive to patients' needs beyond the immediate medical encounter were valued.
CONCLUSIONS: The complexity of cancer care today suggests that efforts to improve communication must be multilevel, acknowledging and addressing patient, clinician, organizational and policy barriers, and facilitators. Measurement tools are needed to assess cancer patients' and family members' experiences with communication over the course of cancer care to provide meaningful, actionable feedback to those seeking to optimize their effectiveness in communicating with patients with cancer.
Long-term surveillance mammography and mortality in older women with a history of early stage invasive breast cancer
Annual surveillance mammograms in older long-term breast cancer survivors are recommended, but this recommendation is based on little evidence and with no guidelines on when to stop. Surveillance mammograms should decrease breast cancer mortality by detecting second breast cancer events at an earlier stage. We examined the association between surveillance mammography beyond 5 years after diagnosis on breast cancer-specific mortality in a cohort of women aged >/= 65 years diagnosed 1990-1994 with early stage breast cancer. Our cohort included women who survived disease free for >/= 5 years (N = 1,235) and were followed from year 6 through death, disenrollment, or 15 years after diagnosis. Asymptomatic surveillance mammograms were ascertained through medical record review. We used Cox proportional hazards regression stratified by follow-up year to calculate the association between time-varying surveillance mammography and breast cancer-specific and other-than-breast mortality adjusting for site, stage, primary surgery type, age and time-varying Charlson Comorbidity Index. The majority (85 %) of the 1,235 5-year breast cancer survivors received >/= 1 surveillance mammogram in years 5-9 (yearly proportions ranged from 48 to 58 %); 82 % of women received >/= 1 surveillance mammogram in years 10-14. A total of 120 women died of breast cancer and 393 women died from other causes (average follow-up 7.3 years). Multivariable models and lasagna plots suggested a modest reduction in breast cancer-specific mortality with surveillance mammogram receipt in the preceding year (IRR 0.82, 95 % CI 0.56-1.19, p = 0.29); the association with other-cause mortality was 0.95 (95 % CI 0.78-1.17, p = 0.64). Among older breast cancer survivors, surveillance mammography may reduce breast cancer-specific mortality even after 5 years of disease-free survival. Continuing surveillance mammography in older breast cancer survivors likely requires physician-patient discussions similar to those recommended for screening, taking into account comorbid conditions and life-expectancy.
Knowledge of and perceived need for evidence-based education about antipsychotic medications among nursing home leadership and staff
BACKGROUND/OBJECTIVES: Antipsychotic use is common in US nursing homes, despite evidence of increased risk of morbidity and mortality, and limited efficacy in older adults with dementia. Knowledge, attitudes, and beliefs regarding antipsychotic use among nursing home staff are unclear. The study aim was to describe nursing home leadership and direct care staff members' knowledge of antipsychotic risks, beliefs and attitudes about the effectiveness of antipsychotics and nonpharmacologic management of dementia-related behaviors, and perceived need for evidence-based training about antipsychotic medication safety.
DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: Survey of leadership and direct care staff of nursing homes in Connecticut was conducted in June 2011. Questionnaire domains included knowledge of antipsychotic risks, attitudes about caring for residents with dementia, satisfaction with current behavior management training, beliefs about antipsychotic effectiveness, and need for staff training about antipsychotics and behavior management.
RESULTS: A total of 138 nursing home leaders and 779 direct care staff provided useable questionnaires. Only 24% of nursing home leaders identified at least 1 severe adverse effect of antipsychotics; 13% of LPNs and 12% of RNs listed at least 1 severe adverse effect. Fifty-six percent of direct care staff believed that medications worked well to manage resident behavior. Leaders were satisfied with the training that staff received to manage residents with challenging behaviors (62%). Fifty-five percent of direct care staff felt that they had enough training on how to handle difficult residents; only 37% felt they could do so without using medications.
CONCLUSIONS: Findings suggest that a comprehensive multifaceted intervention designed for nursing homes should aim to improve knowledge of antipsychotic medication risks, change beliefs about appropriateness and effectiveness of antipsychotics for behavior management, and impart strategies and approaches for nonpharmacologic behavior management. Elsevier Inc. All rights reserved.
INTRODUCTION: There is no comprehensive, systematic analysis of the vitamin D status of prisoners in the scientific literature.
OBJECTIVE: To investigate the vitamin D status and its determinants in US prison inmates.
HYPOTHESIS: Given the uniformity of dietary intake amongst inmates, vitamin D status will be determined by non-dietary factors such as skin pigmentation, security level-, and the duration of incarceration.
SUBJECTS AND METHODS: A retrospective study of 526 inmates (males, n = 502, age 48.6±12.5 years; females, n = 24, age 44.1±12.2) in Massachusetts prisons. Vitamin D sufficiency, insufficiency, and deficiency were respectively defined as a 25(OH)D concentration 75 nmol/L; 50 to 75 nmol/L; and/L. The Massachusetts Department of Correction Statement of Nutritional Adequacy stated that each inmate received the recommended daily allowance of vitamin D daily. Security level of incarceration was designated as minimum, medium, and maximum. Racial groups were categorized as Black, white, Asian, and Others.
RESULTS: Serum 25(OH)D levels peaked in summer and autumn, and decreased in winter and spring. Vitamin D deficiency occurred in 50.5% of blacks, 29.3% of whites, and 14.3% of Asian inmates (p = 0.007). Black inmates had significantly lower serum 25(OH)D level than white inmates at the maximum security level (p = 0.015), medium security level (p = 0.001), but not at the minimum security level (p = 0.40). After adjusting for covariates black inmates at a maximum security level had a four-fold higher risk for vitamin D deficiency than white inmates at the same security level (OR 3.9 [95% CI 1.3-11.7].
CONCLUSIONS: The vitamin D status of prison inmates is determined by skin pigmentation, seasons, and the security level of incarceration.
Interspecies Systems Biology Uncovers Metabolites Affecting C. elegans Gene Expression and Life History Traits
Diet greatly influences gene expression and physiology. In mammals, elucidating the effects and mechanisms of individual nutrients is challenging due to the complexity of both the animal and its diet. Here, we used an interspecies systems biology approach with Caenorhabditis elegans and two of its bacterial diets, Escherichia coli and Comamonas aquatica, to identify metabolites that affect the animal's gene expression and physiology. We identify vitamin B12 as the major dilutable metabolite provided by Comamonas aq. that regulates gene expression, accelerates development, and reduces fertility but does not affect lifespan. We find that vitamin B12 has a dual role in the animal: it affects development and fertility via the methionine/S-Adenosylmethionine (SAM) cycle and breaks down the short-chain fatty acid propionic acid, preventing its toxic buildup. Our interspecies systems biology approach provides a paradigm for understanding complex interactions between diet and physiology.
Diet affects cellular metabolism and organismal life history traits. Pang and Curran (2014) use Caenorhabditis elegans and its bacterial diets to unveil genetic perturbations in proline catabolism that shorten lifespan, but, only on specific Escherichia coli diets, thereby unveiling a genome-encoded adaptive response to different nutritional states.
Tissue-dependent T Cell Apoptosis and Transcriptional Regulation of Memory CD8+T Cell Differentiation During Viral Infections: A Dissertation
Activation and proliferation of antigen-specific T cells is the hallmark of an anti-viral immune response. Effector T cells generated during an immune response are heterogeneous in regards to their ability to populate the memory pool once the immune response has resolved. Initial T cell activation takes place in the lymphoid organs, after which T cells migrate into the non-lymphoid tissues. The presence of memory T cells at non-lymphoid tissue sites has been shown to be critical for protection against secondary virus challenge. Our lab has previously demonstrated that during and after the resolution of the immune response to Lymphocytic choriomeningitis virus (LCMV) CD8+T cells in the nonlymphoid tissues are more resistant to apoptosis than those in the lymphoid organs. This stability of T cells in the non-lymphoid tissues may be critical in ensuring protection against a secondary virus challenge.
Mechanisms regulating tissue-dependent differences in CD8+T cell apoptosis were studied in an acute LCMV infection model. Virus-specific CD8+T cells from lymphoid (spleen, mesenteric lymph nodes (MLN), inguinal lymph nodes (ILN)) and non-lymphoid tissues (peritoneal exudate cells (PEC), fat-pads) were compared for expression of surface antigenic markers known to correlate with a memory phenotype. Non-lymphoid tissues were enriched in IL-7Rhi, KLRG-1lo, CD27hi and CXCR3hi virus-specific CD8+ T cells, and the presence of these antigenic markers correlated with increased memory potential and survival. Transcription factors in addition to cell surface antigens were assessed as correlates of resistance to apoptosis. Virus-specific CD8+T cells in the nonlymphoid tissues were enriched in cells expressing T cell factor-1 (TCF-1), which correlated with increased memory potential and survival. CD8+T cells in the peritoneum of TCF-1-deficient mice had decreased survival during resolution of the immune response to LCMV, suggesting a role for TCF-1 in promoting survival in the non-lymphoid tissues.
As an additional mechanism, I investigated whether apoptosis-resistant CD8+T cells migrate to non-lymphoid tissues and contribute to tissue-dependent apoptotic differences. CXCR3+ CD8+T cells resisted apoptosis and accumulated in the lymph nodes of mice treated with FTY720, which blocks the export of lymph node cells into the peripheral tissues. The PECs expressed increased amounts of CXCR3 ligands, CXCL9 and CXCL10, which may have recruited the non-apoptotic cells from the lymph nodes. By adoptively transferring splenic T cells into the spleen or PEC environment I showed that the peritoneal environment through a yet undefined factor promoted survival of CD8+T cells. In this study I have elucidated the mechanisms by which CD8+T cells preferentially survive in the non-lymphoid tissues. I found that non-lymphoid tissues were enriched in memory-phenotype CD8+T cells which were intrinsically resistant to apoptosis irrespective of the tissue environment. Furthermore, apoptosisresistant CD8+T cells may preferentially migrate into the non-lymphoid tissues where the availability of tissue-specific factors may enhance memory cell survival.
Few transcription factors have been identified that regulate CD8+T cell effector-memory differentiation during an immune response. In this thesis, I have also studied the mechanism by which the transcription factor Blimp-1 regulates the generation of effector and memory CD8+T cells. Blimp-1 is known to repress a large number of target genes, and ChIP (chromatin immunoprecipitation) sequencing analysis done by Dr. HyunMu Shin in the lab of Dr. Leslie J. Berg identified CD25 (IL-2Rα) and CD27 as potential targets of Blimp-1. I found that Blimp-1-deficient CD8+T cells had sustained expression of CD25 (IL-2Rα) and CD27 during peak and resolution of the immune response to LCMV. By performing adoptive transfers of CD25hi and CD27hi CD8+T cells I showed that CD25 and CD27 expression on CD8+T cells during resolution of the immune response correlates with enhanced survival. Silencing Il2rα and Cd27 expression reduced the Blimp-1-deficient CD8+T cell response, suggesting that sustained expression of CD25 and CD27 was in part responsible for the enhanced CD8+T cell response seen in the Blimp-1-deficient mice. Furthermore, our collaborator Dr. HyunMu Shin showed that CD25 and CD27 are direct targets of Blimp-1, and that Blimp-1 recruits histone modifying enzymes to Il2rα and Cd27 loci to suppress their expression during the peak of the anti-viral immune response. This study identifies one of the mechanisms by which Blimp-1 regulates the balance between generation of effector and memory CD8+T cells.
In this thesis work I also studied the function of the transcription factor ROG (Repressor of GATA-3) in regulating in vivo T cell responses during both acute and chronic LCMV infection. ROG-deficient mice had increased CD8+T cell responses during an acute LCMV infection. ROG deficiency also led to the generation of memory T cells with an enhanced recall response compared to WT controls. By using LCMV-specific P14+ TCR transgenic ROG-deficient CD8+T cells these defects were shown to be T cell intrinsic. ROG-deficient mice had enhanced CD8+T cell responses and viral clearance during a persistent high dose LCMV Clone 13 infection. During chronic LCMV infection ROG-deficient mice also had increased lung pathology and mortality. The results indicate that ROG negatively regulates T cell responses and memory generation during both acute and chronic LCMV infection.
The studies highlighted in this thesis elucidate the mechanisms promoting CD8+T cell survival in non-lymphoid tissues as well as transcription factormediated regulation of memory CD8+T cell differentiation. Knowledge of this will help us better understand T cell immunity after infections and may eventually help develop better vaccines.
Understanding the experiences of women who have experienced perinatal depression may help inform needed changes in how health care professionals and organizations screen, diagnose, and treat perinatal depression.
The age-dependent decline in the self-renewal capacity of stem cells plays a critical role in aging, but the precise mechanisms underlying this decline are not well understood. By limiting proliferative capacity, senescence is thought to play an important role in age-dependent decline of stem cell self-renewal, although direct evidence supporting this hypothesis is largely lacking. We have previously identified the E3 ubiquitin ligase Smurf2 as a critical regulator of senescence. In this study, we found that mice deficient in Smurf2 had an expanded hematopoietic stem cell (HSC) compartment in bone marrow under normal homeostatic conditions, and this expansion was associated with enhanced proliferation and reduced quiescence of HSCs. Surprisingly, increased cycling and reduced quiescence of HSCs in Smurf2-deficient mice did not lead to premature exhaustion of stem cells. Instead, HSCs in aged Smurf2-deficient mice had a significantly better repopulating capacity than aged wild-type HSCs, suggesting that decline in HSC function with age is Smurf2 dependent. Furthermore, Smurf2-deficient HSCs exhibited elevated long-term self-renewal capacity and diminished exhaustion in serial transplantation. As we found that the expression of Smurf2 was increased with age and in response to regenerative stress during serial transplantation, our findings suggest that Smurf2 plays an important role in regulating HSC self-renewal and aging.
Summary of Project
Background: Over the last several decades, mindfulness and programs in mind-body stress reduction (MBSR) have emerged as potential therapeutic options for patients with medical conditions such as depression, anxiety, chronic pain, fibromyalgia, insomnia, post-myocardial infarction treatment, and others. Evidence has also emerged that mindfulness may be an effective tool for medical students and healthcare practitioners in reducing stress and anxiety associated with training and practice. It has also shown promise for improving empathy and job satisfaction, while possibly preventing burn-out.
Objectives: This project aimed to study the role that mindfulness may play as an adjunct therapy for patients with chronic diseases, as well as its benefits for medical students and healthcare practitioners.
Methods: Online lectures and published articles were reviewed for studies that evaluated mindfulness as a treatment for chronic medical conditions and as a part of training for medical students and healthcare workers.
Results: (1) Mindfulness as a therapeutic option for patients with chronic medical conditions: Mindfulness and MBSR have been investigated as potential adjunct therapies for a wide range of chronic medical conditions. Investigation into its role in alleviating suffering has grown significantly, with a growing number of studies published in recent years. While individual trials have shown promising results, meta-analyses describe the challenge of aggregating data due to poor quality or inconsistent methodologies across studies. For example, authors of one meta-analysis found 64 relevant studies but could only include 20 of these in their analysis. (2) Mindfulness and healthcare professionals: The articles identified highlight the negative impact that stress can have on medical students and healthcare professionals. The documented negative effects of stress on healthcare workers include anxiety, depression, decreased job satisfaction, diminished personal relationships, and psychological distress. Professional effectiveness may decrease and patients may not get optimal care when practitioners are under severe stress. Mindfulness has been shown to positively benefit students and healthcare practitioners by reducing stress and anxiety, while increasing empathy and job satisfaction. Limitations to these findings are discussed below.
Conclusions: Mindfulness and MBSR may be beneficial, cost-effective interventions for many chronic conditions, including both mental and physical ailments. The data in support of mindfulness and MBSR as an adjunct therapy was strongest for alleviating pain, anxiety, and a wide range of symptoms associated with chronic medical conditions. Physical and mental conditions have been shown to improve with mindfulness and MBSR treatment. The studies reviewed showed potential benefits of mindfulness and MBSR on medical students and healthcare workers. However, future studies are needed that include more robust sample sizes, limit biases such as self-selecting subjects, include adequate control groups, maintain consistent methodology (such as standardized training of mindfulness and MBSR instructors) and statistical analysis across studies, measure long-term effects, and have more objectively defined study end-points.
Should patients with acute coronary disease be stratified for management according to their risk? Derivation, external validation and outcomes using the updated GRACE risk score
OBJECTIVES: Risk scores are recommended in guidelines to facilitate the management of patients who present with acute coronary syndromes (ACS). Internationally, such scores are not systematically used because they are not easy to apply and some risk indicators are not available at first presentation. We aimed to derive and externally validate a more accurate version of the Global Registry of Acute Coronary Events (GRACE) risk score for predicting the risk of death or death/myocardial infarction (MI) both acutely and over the longer term. The risk score was designed to be suitable for acute and emergency clinical settings and usable in electronic devices.
DESIGN AND SETTING: The GRACE risk score (2.0) was derived in 32 037 patients from the GRACE registry (14 countries, 94 hospitals) and validated externally in the French registry of Acute ST-elevation and non-ST-elevation MI (FAST-MI) 2005.
PARTICIPANTS: Patients presenting with ST-elevation and non-ST elevation ACS and with long-term outcomes.
OUTCOME MEASURES: The GRACE Score (2.0) predicts the risk of short-term and long-term mortality, and death/MI, overall and in hospital survivors.
RESULTS: For key independent risk predictors of death (1 year), non-linear associations (vs linear) were found for age (p
CONCLUSIONS: The updated GRACE risk score has better discrimination and is easier to use than the previous score based on linear associations. GRACE Risk (2.0) performed equally well acutely and over the longer term and can be used in a variety of clinical settings to aid management decisions.
Diet quality has not been well studied in relation to positive psychological traits. Our purpose was to investigate the relationship between optimism and diet quality in postmenopausal women enrolled in the Women's Health Initiative observational study (OS) and clinical trials (CTs), and to determine whether optimism was associated with diet change after a 1-year dietary intervention. Diet quality was scored with the Alternate Healthy Eating Index (AHEI) and optimism assessed with the Life Orientation Test-Revised. Baseline characteristics were compared across AHEI quintiles or optimism tertiles using regression models with each variable of interest as a function of quintiles or tertiles (OS, n=87,630; CT, n=65,360). Association between optimism and baseline AHEI and change in AHEI over 1 year were tested using multivariate linear regression (CT, n=13,645). Potential interaction between optimism and trial arm and demographic/lifestyle factors on AHEI change was tested using likelihood ratio test (CT intervention, n=13,645; CT control, n=20,242). Women reporting high AHEI were non-Hispanic white, educated, physically active, past or never smokers, hormone therapy users, had lower body mass index and waist circumference, and were less likely to have chronic conditions. In the CT intervention, higher optimism was associated with higher AHEI at baseline and with greater change over 1 year (P=0.001). Effect modification by intervention status was observed (P=0.014), whereas control participants with highest optimism achieved threefold greater AHEI increase compared with those with the lowest optimism. These data support a relationship between optimism and dietary quality score in postmenopausal women at baseline and over 1 year.
An AHA Science Advisory recommending that physicians intervene more assertively to get patients to adopt healthier lifestyles, directly targeting smoking, obesity, poor diet, and physical inactivity.
OBJECTIVE: To determine the feasibility, acceptability, and outcomes of a telephone counseling intervention promoting colorectal cancer (CRC) screening when patients are referred for counseling by primary care providers (PCPs). Study Design: Interventional cohort study with no formal control group.
METHODS: PCPs in 3 practices were prompted to address CRC screening in patient encounters and, if appropriate, to recommend referral for telephone counseling. A telephone counselor called referred patients, made an appointment for a counseling call, and mailed an educational booklet to patients. Counseling included education about CRC and screening tests, motivational interviewing, barrier counseling, and facilitated referral for colonoscopy or mailing of a fecal occult blood testing kit. About 7 months following counseling, electronic records were searched for evidence of colonoscopy.
RESULTS: PCPs addressed CRC screening with 1945 patients, most of whom were up-to-date with CRC testing, recommended counseling referral to 362, and of these 180 (49.7%) accepted the referral. A total of 140 (77.8%) of referred patients were contacted and 67 (37.2%) received counseling. After counseling 93.9% were planning on CRC screening compared with 54.6% at the beginning of the call. Of those planning a colonoscopy, 53.2% received one within 7 months.
CONCLUSIONS: Referring patients for telephone counseling to promote CRC screening may be feasible and acceptable to PCPs and to some patients, and may increase CRC screening. Further evaluation of the intervention may be warranted to compare the rate of screening associated with the intervention to rates related to usual care and to other interventions.
BACKGROUND: Alcohol and caffeine intakes may play a role in the development of sudden cardiac death (SCD) because of their effects on cholesterol, blood pressure, heart rate variability, and inflammation.
OBJECTIVE: Our objective was to examine the association between long-term alcohol and caffeine intakes and risk of SCD in women.
DESIGN: We examined 93,676 postmenopausal women who participated in the Women's Health Initiative Observational Study. Women were enrolled between 1993 and 1998 and were followed until August 2009. Women completed a food-frequency questionnaire at baseline and again at year 3. We modeled exposure to alcohol 3 ways: by using baseline intake only, a cumulative average of baseline and year 3 intake, and the most recent reported intake (a simple time-varying analysis).
RESULTS: Intake of 5-15 g alcohol/d (about one drink) was associated with a nonsignificantly reduced risk of SCD compared with 0.1-5 g/d of baseline intake (HR: 0.64; 95% CI: 0.40, 1.02), of cumulative average intake (HR: 0.69; 95% CI: 0.43, 1.11), and of most recent intake (HR: 0.58; 95% CI: 0.35, 0.96), with adjustment for age, race, income, smoking, body mass index, physical activity, hormone use, and total energy. No association was found between SCD and total caffeine intake (mg/d) or cups of caffeinated coffee, decaffeinated coffee, and caffeinated tea.
CONCLUSIONS: Our results suggest that about one drink per day (or 5.1-15 g/d) may be associated with a reduced risk of SCD in this population; however, this association was only statistically significant for a model using the most recent alcohol intake. Total caffeine, regular coffee, decaffeinated coffee, and regular tea intake were not associated with the risk of SCD.
This trial was registered at clinicaltrials.gov as NCT00000611.
Severe obesity, heart disease, and death among white, african american, and hispanic postmenopausal women
OBJECTIVE: To compare mortality, nonfatal coronary heart disease (CHD), and congestive heart failure (CHF) risk across BMI categories in white, African American, and Hispanic women, with a focus on severe obesity (BMI >/= 40), and examine heterogeneity in weight-related CHD risk.
DESIGN AND METHODS: Among 156,775 Women's Health Initiative observational study and clinical trial participants (September 1993-12 September 2005), multivariable Cox models estimated relative risk for mortality, CHD, and CHF. CHD incidence was calculated by anthropometry, race, and cardiovascular risk factors (CVRF).
RESULTS: Mortality, nonfatal CHD, and CHF incidence generally rose with BMI category. For severe obesity versus normal BMI, hazard ratios (HRs, 95% confidence interval) for mortality were 1.97 (1.77-2.20) in white, 1.55 (1.20-2.00) in African American, and 2.59 (1.55-4.31) in Hispanic women; for CHD, HRs were 2.05 (1.80-2.35), 2.24 (1.57-3.19), and 2.95 (1.60-5.41) respectively; for CHF, HRs were 5.01 (4.33-5.80), 3.60 (2.30-5.62), and 6.05 (2.49-14.69). CVRF variation resulted in substantial variation in CHD rates across BMI categories, even in severe obesity. CHD incidence was similar by race/ethnicity when differences in BMI or CVRF were accounted for.
CONCLUSIONS: Severe obesity increases mortality, nonfatal CHD, and CHF risk in women of diverse race/ethnicity. CVRF heterogeneity contributes to variation in CHD incidence even in severe obesity.