Building a Community Partnership for the Development of Health Ministries Within the African American Community: The Triad Pastors Network.

African Americans continue to have worse health outcomes despite attempts to reduce health disparities. This is due, in part, to inadequate access to healthcare, but also to the health care and medical mistrust experienced by communities of color. Churches and worship centers have historically served as cultural centers of trusted resources for educational, financial, and health information within African American communities and a growing number of collaborations have developed between academic institutions and community/faith entities. Herein, we describe the infrastructure of a true and sustainable partnership developed with > 100 prominent faith leaders within the Piedmont Triad region of North Carolina for the purpose of developing or expanding existing health ministries within houses of worship, to improve health literacy and overall health long-term. The Triad Pastors Network is an asset-based partnership between the Maya Angelou Center for Health Equity at Wake Forest University School of Medicine and faith leaders in the Piedmont Triad region of North Carolina that was created under the guiding principles of community engagement to improve health equity and decrease health disparities experienced by African American communities. A partnership in which co-equality and shared governance are the core of the framework provides an effective means of achieving health-related goals in a productive and efficient manner. Faith-based partnerships are reliable approaches for improving the health literacy needed to address health disparities and inequities in communities of color.

"Ariadne's Thread": Psycho-educational Empowerment Intervention for Patients with Metastatic Breast Cancer.

"Ariadne's thread" is a psycho-educational intervention designed by the Breast Unit and the Clinical Psychology Unit of an Italian Comprehensive Cancer Center and aims to promote empowerment in patients with metastatic breast cancer. It consists of 8 online meetings led by a psycho-oncologist in which informative sessions by patients' referring physicians alternate with moments of stress management techniques. This study aims to investigate (1) the feasibility of the "Ariadne's thread" pilot intervention and (2) the satisfaction and perceived benefits of the pilot intervention. We used a mixed method approach in which (1) it was detected: the number of acceptance to the single session of the intervention by both patients and professionals, the number of help requests by patients, and the number of change of date requests by professionals; (2) semi-structured interviews were conducted with the professionals who participated in the intervention; (3) 2 focus groups were conducted with patients, and (4) a questionnaire was submitted to each of them. The intervention is sustainable from the perspective of the organization, professionals, and patients. In particular, the patients declared perceiving benefits in many aspects: improved relationships with doctors, acceptance of their illness, learning of a relaxation technique, possibility to look at the world with trust and hope, etc. The questionnaires show an improvement in empowerment and satisfaction as a result of the intervention. "Ariadne's thread" is a psycho-educational intervention that effectively addresses the needs of patients with MBC. It can be applied to other contexts (1) if it has been confirmed that similar needs exist or (2) if it can be modified to accommodate other needs.

Effect of Intensive Blood-Pressure Treatment on Patient-Reported Outcomes.

BACKGROUND: The previously published results of the Systolic Blood Pressure Intervention Trial showed that among participants with hypertension and an increased cardiovascular risk, but without diabetes, the rates of cardiovascular events were lower among those who were assigned to a target systolic blood pressure of less than 120 mm Hg (intensive treatment) than among those who were assigned to a target of less than 140 mm Hg (standard treatment). Whether such intensive treatment affected patient-reported outcomes was uncertain; those results from the trial are reported here. METHODS: We randomly assigned 9361 participants with hypertension to a systolic blood-pressure target of less than 120 mm Hg or a target of less than 140 mm Hg. Patient-reported outcome measures included the scores on the Physical Component Summary (PCS) and Mental Component Summary (MCS) of the Veterans RAND 12-Item Health Survey, the Patient Health Questionnaire 9-item depression scale (PHQ-9), patient-reported satisfaction with their blood-pressure care and blood-pressure medications, and adherence to blood-pressure medications. We compared the scores in the intensive-treatment group with those in the standard-treatment group among all participants and among participants stratified according to physical and cognitive function. RESULTS: Participants who received intensive treatment received an average of one additional antihypertensive medication, and the systolic blood pressure was 14.8 mm Hg (95% confidence interval, 14.3 to 15.4) lower in the group that received intensive treatment than in the group that received standard treatment. Mean PCS, MCS, and PHQ-9 scores were relatively stable over a median of 3 years of follow-up, with no significant differences between the two treatment groups. No significant differences between the treatment groups were noted when participants were stratified according to baseline measures of physical or cognitive function. Satisfaction with blood-pressure care was high in both treatment groups, and we found no significant difference in adherence to blood-pressure medications. CONCLUSIONS: Patient-reported outcomes among participants who received intensive treatment, which targeted a systolic blood pressure of less than 120 mm Hg, were similar to those among participants who received standard treatment, including among participants with decreased physical or cognitive function. (Funded by the National Institutes of Health; SPRINT ClinicalTrials.gov number, NCT01206062 .).

Effect of Intensive vs Standard Blood Pressure Treatment Upon Erectile Function in Hypertensive Men: Findings From the Systolic Blood Pressure Intervention Trial.

INTRODUCTION: The effect of intensive blood pressure control upon erectile function in men with hypertension, but without diabetes, is largely unknown. AIM: To examine the effects of intensive systolic blood pressure (SBP) lowering on erectile function in a multiethnic clinical trial of men with hypertension. METHODS: We performed subgroup analyses from the Systolic Blood Pressure Intervention Trial ([SPRINT]; ClinicalTrials.gov: NCT120602, in a sample of 1255 men aged 50 years or older with hypertension and increased cardiovascular disease risk. Participants were randomly assigned to an intensive treatment group (SBP goal of <120 mmHg) or a standard treatment group (SBP goal of <140 mmHg). MAIN OUTCOME MEASURE: The main outcome measure was change in erectile function from baseline, using the 5-item International Index of Erectile Function (IIEF-5) total score, and erectile dysfunction ([ED]; defined as IIEF-5 score ≤21) after a median follow-up of 3 years. RESULTS: At baseline, roughly two-thirds (66.1%) of the sample had self-reported ED. At 48 months after randomization, we determined that the effects of more intensive blood pressure lowering were significantly moderated by race-ethnicity (p for interaction = 0.0016), prompting separate analyses stratified by race-ethnicity. In non-Hispanic whites, participants in the intensive treatment group reported slightly, but significantly better change in the IIEF-5 score than those in the standard treatment group (mean difference = 0.67; 95% CI = 0.03, 1.32; P = 0.041). In non-Hispanic blacks, participants in the intensive group reported slightly worse change in the IIEF-5 score than those in the standard group (mean difference = -1.17; 95% CI = -1.92, -0.41; P = 0.0025). However, in non-Hispanic whites and non-Hispanic blacks, further adjustment for the baseline IIEF-5 score resulted in nonsignificant differences (P > 0.05) according to the treatment group. In Hispanic/other participants, there were no significant differences in change in the IIEF-5 score between the two treatment groups (P = 0.40). In a subgroup of 280 participants who did not report ED at baseline, the incidence of ED did not differ in the two treatment groups (P = 0.53) and was without interaction by race-ethnicity. CLINICAL IMPLICATIONS: The effect of intensive treatment of blood pressure on erectile function was very small overall and likely not of great clinical magnitude. STRENGTH & LIMITATIONS: Although this study included a validated measure of erectile function, testosterone, other androgen, and estrogen levels were not assessed. CONCLUSION: In a sample of male patients at high risk for cardiovascular events but without diabetes, targeting a SBP of less than 120 mm Hg, as compared with less than 140 mm Hg, resulted in statistically significant effects on erectile function that differed in accordance with race-ethnicity, although the clinical importance of the differences may be of small magnitude. Foy CG, Newman JC, Russell GB, et al. Effect of Intensive vs Standard Blood Pressure Treatment Upon Erectile Function in Hypertensive Men: Findings From the Systolic Blood Pressure Intervention Trial. J Sex Med 2020;17:238-248.

Blood Pressure, Sexual Activity, and Erectile Function in Hypertensive Men: Baseline Findings from the Systolic Blood Pressure Intervention Trial (SPRINT).

INTRODUCTION: Erectile function, an important aspect of quality of life, is gaining increased research and clinical attention in older men with hypertension. AIM: To assess the cross-sectional association between blood pressure measures (systolic blood pressure [SBP]; diastolic blood pressure [DBP]; and pulse pressure [PP]) and (i) sexual activity and (ii) erectile function in hypertensive men. METHODS: We performed analyses of 1,255 male participants in a larger randomized clinical trial of 9,361 men and women with hypertension aged ≥50 years. MAIN OUTCOME MEASURES: The main outcome measures were self-reported sexual activity (yes/no) and erectile function using the 5-item International Index of Erectile Function (IIEF-5). RESULTS: 857 participants (68.3%) reported being sexually active during the previous 4 weeks. The mean (SD) IIEF-5 score for sexually active participants was 18.0 (5.8), and 59.9% of the sample reported an IIEF-5 score <21, suggesting erectile dysfunction (ED). In adjusted logistic regression models, neither SBP (adjusted odds ratio = 0.998; P = .707) nor DBP (adjusted odds ratio = 1.001; P = .929) was significantly associated with sexual activity. In multivariable linear regression analyses in sexually active participants, lower SBP (ß = -0.04; P = .025) and higher DBP (ß = 0.05; P = .029) were associated with better erectile function. In additional multivariable analyses, lower PP pressure was associated with better erectile function (ß = -0.04; P = .02). CLINICAL IMPLICATIONS: Blood pressure is an important consideration in the assessment of erectile function in men with hypertension. STRENGTHS & LIMITATIONS: Assessments of blood pressure and clinical and psychosocial variables were performed using rigorous methods in this multi-ethnic and geographically diverse sample. However, these cross-sectional analyses did not include assessment of androgen or testosterone levels. CONCLUSIONS: Erectile dysfunction was highly prevalent in this sample of men with hypertension, and SBP, DBP, and PP were associated with erectile function in this sample. Foy CG, Newman JC, Berlowitz DR, et al. Blood Pressure, Sexual Activity, and Erectile Function in Hypertensive Men: Baseline Findings from the Systolic Blood Pressure Intervention Trial (SPRINT). J Sex Med 2019;16:235-247.

Blood Pressure, Sexual Activity, and Dysfunction in Women With Hypertension: Baseline Findings From the Systolic Blood Pressure Intervention Trial (SPRINT).

INTRODUCTION: Sexual function, an important component of quality of life, is gaining increased research and clinical attention in older women with hypertension. AIM: To assess the association between systolic blood pressure (SBP) and other variables, and sexual activity and sexual dysfunction in hypertensive women. METHODS: Baseline analysis of 635 women participants of a larger randomized clinical trial of 9361 men and women. MAIN OUTCOME MEASURES: Self-reported sexual activity (yes/no), and sexual function using the Female Sexual Function Inventory (FSFI). RESULTS: 452 participants (71.2%) reported having no sexual activity during the previous 4 weeks. The mean (SD) FSFI score for sexually active participants was 25.3 (6.0), and 52.6% of the sample reported a FSFI score ≤26.55 designating sexual dysfunction. In logistic regression models, SBP was not significantly associated with sexual activity (AOR = 1.002; P > .05). Older age (AOR = 0.95, P < .05), and lower education (AOR for < high school vs college degree = 0.29, P < .05) were associated with lower odds of being sexually active, as was living alone versus living with others (AOR = 0.56, P < .05). Higher weekly alcohol consumption was associated with increased odds of being sexually active (AOR = 1.39; P < .05). In logistic regression models among sexually active participants, SBP was not associated with sexual dysfunction (AOR = 1.01; P > .05). Higher depressive symptoms from the Patient Health Questionnaire-9 (PHQ-9) was associated with higher odds of sexual dysfunction (AOR = 1.24, P < .05), as was increased number of physical comorbidities (AOR = 1.25, P < .05). Diuretic use was associated with lower odds of being sexually active in participants with chronic kidney disease (AOR = 0.33, P < .05). CONCLUSION: Younger age, higher education, living with others, and higher weekly alcohol consumption were significantly associated with higher odds of being sexually active in a sample of middle-aged and older women with hypertension. Increased depressive symptoms and increased physical comorbidities were significantly associated with increased odds of sexual dysfunction. SBP was not significantly associated with sexual activity or sexual dysfunction.

The design and rationale of a multicenter clinical trial comparing two strategies for control of systolic blood pressure: the Systolic Blood Pressure Intervention Trial (SPRINT).

BACKGROUND: High blood pressure is an important public health concern because it is highly prevalent and a risk factor for adverse health outcomes, including coronary heart disease, stroke, decompensated heart failure, chronic kidney disease, and decline in cognitive function. Observational studies show a progressive increase in risk associated with blood pressure above 115/75 mm Hg. Prior research has shown that reducing elevated systolic blood pressure lowers the risk of subsequent clinical complications from cardiovascular disease. However, the optimal systolic blood pressure to reduce blood pressure-related adverse outcomes is unclear, and the benefit of treating to a level of systolic blood pressure well below 140 mm Hg has not been proven in a large, definitive clinical trial. PURPOSE: To describe the design considerations of the Systolic Blood Pressure Intervention Trial (SPRINT) and the baseline characteristics of trial participants. METHODS: The Systolic Blood Pressure Intervention Trial is a multicenter, randomized, controlled trial that compares two strategies for treating systolic blood pressure: one targets the standard target of <140 mm Hg, and the other targets a more intensive target of <120 mm Hg. Enrollment focused on volunteers of age ≥50 years (no upper limit) with an average baseline systolic blood pressure ≥130 mm Hg and evidence of cardiovascular disease, chronic kidney disease, 10-year Framingham cardiovascular disease risk score ≥15%, or age ≥75 years. The Systolic Blood Pressure Intervention Trial recruitment also targeted three pre-specified subgroups: participants with chronic kidney disease (estimated glomerular filtration rate <60 mL/min/1.73 m(2)), participants with a history of cardiovascular disease, and participants 75 years of age or older. The primary outcome is first the occurrence of a myocardial infarction (MI), acute coronary syndrome, stroke, heart failure, or cardiovascular disease death. Secondary outcomes include all-cause mortality, decline in kidney function or development of end-stage renal disease, incident dementia, decline in cognitive function, and small-vessel cerebral ischemic disease. RESULTS: Between 8 November 2010 and 15 March 2013, Systolic Blood Pressure Intervention Trial recruited and randomized 9361 people at 102 clinics, including 3331 women, 2648 with chronic kidney disease, 1877 with a history of cardiovascular disease, 3962 minorities, and 2636 ≥75 years of age. LIMITATIONS: Although the overall recruitment target was met, the numbers recruited in the high-risk subgroups were lower than planned. CONCLUSIONS: The Systolic Blood Pressure Intervention Trial will provide important information on the risks and benefits of intensive blood pressure treatment targets in a diverse sample of high-risk participants, including those with prior cardiovascular disease, chronic kidney disease, and those aged ≥75 years.

Translating the Dietary Approaches to Stop Hypertension (DASH) diet for use in underresourced, urban African American communities, 2010.

INTRODUCTION: Randomized trials have demonstrated the effectiveness of the Dietary Approaches to Stop Hypertension (DASH) program for lowering blood pressure; however, program participation has been limited in some populations. The objective of this pilot study was to test the feasibility of using a culturally modified version of DASH among African Americans in an underresourced community. METHODS: This randomized controlled pilot study recruited African Americans in 2 North Carolina neighborhoods who had high blood pressure and used fewer than 3 antihypertension medications. We offered 2 individual and 9 group DASH sessions to intervention participants and 1 individual session and printed DASH educational materials to control participants. We collected data at baseline (March 2010) and 12 weeks (June 2010). RESULTS: Of 152 potential participants, 25 were randomly assigned to either the intervention (n = 14) or the control (n = 11) group; 22 were women, and 21 were educated beyond high school. At baseline, mean blood pressure was 130/78 mm Hg; 19 participants used antihypertension medications, and mean body mass index was 35.9 kg/m(2). Intervention participants attended 7 of 9 group sessions on average. After 12 weeks, we observed significant increases in fruit and vegetable consumption and increases in participants' confidence in their ability to reduce salt and fat consumption and eat healthier snacks in intervention compared with control participants. We found no significant decreases in blood pressure. CONCLUSION: Implementation of a culturally modified, community-based DASH intervention was feasible in our small sample of African Americans, which included people being treated for high blood pressure. Future studies should evaluate the long-term effect of this program in a larger sample.

Use of coaching and technology to improve blood pressure control in Black women with hypertension: Pilot randomized controlled trial study.

Hypertension is the main cause of cardiovascular disease, especially in women. Black women (58%) are affected by higher rates of hypertension than other racial/ethnic groups contributing to increased cardio-metabolic disorders. To decrease blood pressure (BP) in this population, a pilot randomized controlled trial was conducted to examine the effects of Interactive Technology Enhanced Coaching (ITEC) versus Interactive Technology (IT) alone in achieving BP control, adherence to antihypertensive medication, and adherence to lifestyle modifications among Black women diagnosed with and receiving medication for their hypertension. Participants completed a 6-week Chronic Disease Self-Management Program (CDSMP), and 83 participants were randomly assigned to ITEC versus IT. Participants were trained to use three wireless tools and five apps that were synchronized to smartphones to monitor BP, weight, physical activity (steps), diet (caloric and sodium intake), and medication adherence. Fitbit Plus, a cloud-based collaborative care platform was used to collect, track, and store data. Using a mixed-effects repeated measures model, the main effect of group means indicated no significant difference between the treatment and referent groups on study variables. The main effect of time indicated significant differences between repeated measures for systolic BP (p < .0001), weight (p < .0001), and steps (p = .018). An interaction effect revealed differences over time and was significant for study measures except diastolic BP. An important goal of this preliminary analysis is to help Black women prioritize self-care management in their everyday environment. Future research is warranted in a geographically broader population of hypertensive Black women.

Gender, Age and COVID-19 Vaccination Status in African American Adult Faith-Based Congregants in the Southeastern United States.

OBJECTIVES: The COVID-19 pandemic has revealed significant differences in COVID-19 vaccination rates, with African Americans reporting lower rates compared to other racial and ethnic groups. The purpose of these analyses was to assess whether COVID-19 vaccination status differed according to age in a sample of 1,240 African American adult congregants of faith-based organizations ages 18 years or older, and to examine whether this association was moderated by gender. DESIGN: We developed and administered a 75-item cross-sectional survey, the Triad Pastor's Network COVID-19 and COVID-19 Vaccination survey, to assess experiences and perceptions regarding the COVID-19 virus and vaccines. We assessed the association between age and having received > 1 dose of a COVID-19 vaccine using unadjusted and multivariable binary logistic regression models, and the interaction of age and gender with COVID-19 vaccination status in a multivariable model. RESULTS: Approximately 86% of participants reported having received ≥ 1 dose of a COVID-19 vaccine. The mean age (standard deviation) of the sample was 51.33 (16.62) years, and 70.9% of the sample was comprised of women. The age by gender interaction term in the multivariable model was significant (p = 0.005), prompting additional analyses stratified by gender. In women, increased age was significantly associated with higher odds of COVID-19 vaccination (odds ratio = 1.09; 95% Confidence Interval 1.06, 1.11; p < 0.001). In men, the association was not significant (p = 0.44). CONCLUSIONS: Older age was positively associated with COVID-19 vaccination in African American women, but not African American men, which may inform strategies to increase vaccination rates.

Assessing the Role of Trust in Public Health Agencies and COVID-19 Vaccination Status Among a Community Sample of African Americans in North Carolina.

BACKGROUND: Mistrust of the government and medical establishments are prominent reasons for vaccine hesitancy among African Americans (AAs). As COVID-19 research evolves in real time with some uncertainties remaining, AA communities may be less trusting of public health agencies. The purpose of these analyses was to assess the association between trust in public health agencies that recommend the COVID-19 vaccination and COVID-19 vaccination status among AAs in North Carolina. METHODS: A 75-item cross-sectional survey, the Triad Pastors Network COVID-19 and COVID-19 Vaccination survey, was developed and administered to African Americans in North Carolina. Multivariable logistic regression was used to examine the association between levels of trust in public health agencies who recommend the COVID-19 vaccine and COVID-19 vaccination status among AAs. RESULTS: Of the 1157 AAs included in these analyses, approximately 14% of AAs had not received the COVID-19 vaccine. These findings indicated that lower levels of trust in public health agencies significantly decreased the odds of getting the COVID-19 vaccination compared to those with higher levels of trust among AAs. The most trusted source for information on COVID-19 included federal agencies among all respondents. Among the vaccinated, primary care physicians were another trusted source of information. Pastors were another trusted source for those willing to be vaccinated. CONCLUSIONS: Despite the majority of the respondents in this sample receiving the COVID-19 vaccine, subgroups of AAs remain unvaccinated. Federal agencies have a high level of trust among AA adults; however, innovative approaches are needed to reach AAs who remain unvaccinated.

Associations of work hours with carotid intima-media thickness and ankle-brachial index: the Multi-Ethnic Study of Atherosclerosis (MESA).

OBJECTIVES: Long working hours may be associated with cardiovascular disease (CVD). The objective was to investigate cross-sectional associations of work hours with carotid intima-media thickness (CIMT) and ankle-brachial index (ABI). METHODS: Participants were 1694 women and 1868 men from the Multi-Ethnic Study of Atherosclerosis. CIMT and ABI were measured using standard protocols. Information on work hours was obtained from questionnaires. Mean values of CIMT and ABI were examined across five categories of hours worked per week (≤20, 21-39, 40, 41-50 and >50) using analysis of variance/analysis of covariance. p Values for trend were obtained from linear regression models. RESULTS: Mean age of participants was 56.9±8.4 years; 52.4% were men. Distinct patterns of association between work hours and the subclinical CVD biomarkers were found for women and men, although this heterogeneity by gender was not statistically significant. Among women only, work hours were positively associated with common (but not internal) CIMT (p=0.073) after full risk factor adjustment. Compared with women working 40 h, those working >50 h were more likely to have an ABI <1 (vs 1-1.4) (OR=1.85, 95% CI 1.01 to 3.38). In men, work hours and ABI were inversely associated (p=0.046). There was some evidence that the association between work hours and ABI was modified by occupational category (interaction p=0.061). Among persons classified as management/professionals, longer work hours was associated with lower ABI (p=0.015). No significant associations were observed among other occupational groups. CONCLUSIONS: Working longer hours may be associated with subclinical CVD. These associations should be investigated using longitudinal studies.

An open-label expanded access study of lapatinib and capecitabine in patients with HER2-overexpressing locally advanced or metastatic breast cancer.

BACKGROUND: The Lapatinib Expanded Access Program (LEAP) was designed to provide access to lapatinib plus capecitabine for HER2-positive metastatic breast cancer patients who previously received an anthracycline, a taxane, and a trastuzumab and had no other treatment options. PATIENTS AND METHODS: LEAP opened globally and enrollment continued until lapatinib received regulatory approval in each participating country. Patients were assessed for progression-free survival (PFS) and overall survival (OS) and monitored for serious adverse events (SAEs). RESULTS: As of 30 September 2008, 4283 patients from 45 countries enrolled in LEAP. The median treatment duration was 24.7 weeks. The most common drug-related SAEs were diarrhea (9.7%), vomiting (4.3%), and nausea (2.4%) and were mainly grade 3 or higher. The incidences of special interest SAEs were decreased left ventricle ejection fraction (0.5%), interstitial lung disease/pneumonitis (0.2%), and serious hepatobiliary events (0.4%). This safety profile is consistent with the overall lapatinib program. The median PFS and OS were 21.1 [95% confidence interval (CI) = 20.1-22.3] and 39.6 (95% CI = 37.7-40.7) weeks, respectively (n = 4006). Subgroup analysis showed longer PFS and OS in patients who had not received prior capecitabine. CONCLUSIONS: These results demonstrate the safety and efficacy of lapatinib in a broader patient population compared with a clinical trial.

Clinical and pharmacological phase I evaluation of Exherin (ADH-1), a selective anti-N-cadherin peptide in patients with N-cadherin-expressing solid tumours.

BACKGROUND: Upregulation of N-cadherin promotes dysregulated cell growth, motility, invasiveness, plus maintenance of vascular stability and is associated with cancer progression in several human tumour types. N-cadherin is expressed also on tumour cells and the anti-N-cadherin cyclic pentapeptide ADH-1, tested in the present study, can exert a direct antitumour effect. PATIENTS AND METHODS: Adult patients with advanced solid malignancies expressing N-cadherin on tumour biopsies carried out in the previous 12 months received escalating i.v. doses of ADH-1 given weekly (initially for 3 of 4 weeks, then every week). Plasma pharmacokinetics (PK) was studied at cycle 1. Blood flow changes were assessed after first dosing in all patients treated in the initial regimen. RESULTS: In all, 129 patients were screened, 65 (50%) were N-cadherin positive, and 30 were enrolled. The doses ranged from 150 to 2400 mg/m(2); no maximum tolerated dose was reached. Treatment was well tolerated with asthenia as the most frequent adverse event. Two patients with ovarian cancer showed prolonged disease stabilisation while one patient with fallopian tube carcinoma achieved a mixed response. PK was linear in the range of doses tested. CONCLUSION: ADH-1 is the first anti-N-cadherin compound tested in humans. In N-cadherin-positive patients, ADH-1 showed an acceptable toxicity profile, linear PK and hints of antitumour activity in gynaecological cancers.

Association of Total Medication Burden With Intensive and Standard Blood Pressure Control and Clinical Outcomes: A Secondary Analysis of SPRINT.

Total medication burden (antihypertensive and nonantihypertensive medications) may be associated with poor systolic blood pressure (SBP) control. We investigated the association of baseline medication burden and clinical outcomes and whether the effect of the SBP intervention varied according to baseline medication burden in SPRINT (Systolic Blood Pressure Intervention Trial). Participants were randomized to intensive or standard SBP goal (below 120 or 140 mm Hg, respectively); n=3769 participants with high baseline medication burden (≥5 medications) and n=5592 with low burden (<5 medications). PRIMARY OUTCOME: differences in SBP. SECONDARY OUTCOMES: 8-item Morisky Medication Adherence Scale and modified Treatment Satisfaction Questionnaire for Medications measured at baseline and 12 months and incident cardiovascular disease events and serious adverse events throughout the trial. Participants in the intensive group with high versus low medication burden were less likely to achieve their SBP goal at 12 months (risk ratio, 0.91; 95% CI, 0.85-0.97) but not in the standard group (risk ratio, 0.98; 95% CI, 0.93-1.03; Pinteraction<0.001). High medication burden was associated with increased cardiovascular disease events (hazard ratio, 1.39; 95% CI, 1.14-1.70) and serious adverse events (hazard ratio, 1.34; 95% CI, 1.24-1.45), but the effect of intensive versus standard treatment did not vary between medication burden groups (Pinteraction>0.5). Medication burden had minimal association with adherence or satisfaction. High baseline medication burden was associated with worse intensive SBP control and higher rates of cardiovascular disease events and serious adverse events. The relative benefits and risks of intensive SBP goals were similar regardless of medication burden. CLINICAL TRIAL REGISTRATION- URL: http://www. CLINICALTRIALS: gov. Unique identifier: NCT01206062.

Visceral fat and prevalence of hypertension among African Americans and Hispanic Americans: findings from the IRAS family study.

BACKGROUND: We examined the relationship between visceral adipose tissue (VAT), independent of overall adiposity, and prevalent hypertension among adults enrolled in the Insulin Resistance Atherosclerosis (IRAS) Family Study. We also examined the role of insulin sensitivity (S(I)) upon hypertension. This was a cross-sectional epidemiological study in which African-American and Hispanic-American families were recruited from three clinical sites. The main outcome measure was prevalent hypertension, as defined by standardized protocol. METHODS: The relationship between VAT and prevalent hypertension was examined in adjusted marginal models among 1,582 participants. All continuous variables were standardized. RESULTS: A significant VAT by gender interaction prompted separate analyses for VAT according to gender. Further adjustment for S(I) was performed to determine its potential roles in the VAT-hypertension relationship. The mean age (s.d.) of the sample was 41.3 (13.8) years, with a mean body mass index (BMI) (s.d.) of 28.7 (6.0) kg/m2. Women comprised 58.5% of the sample (N = 925), and Hispanic Americans comprised 69.2% of the sample (N = 1,095). One in five participants (21.2%) had prevalent hypertension. In women, VAT was significantly associated with hypertension, independent of BMI (odds ratio (OR) = 1.49, P = 0.006). African-American women demonstrated increased odds of prevalent hypertension compared to Hispanic-American women (OR = 3.08, P < 0.001). Among men, VAT was not associated with hypertension independent of BMI, and BMI explained a significant amount of the variation in hypertension. CONCLUSIONS: A significant relationship may exist between VAT and hypertension among women, but not among men. The relationship between VAT and hypertension in women was not associated with insulin resistance.

Gender, blood pressure, and cardiovascular and renal outcomes in adults with hypertension from the Systolic Blood Pressure Intervention Trial.

BACKGROUND: To determine if the effects of intensive lowering of systolic blood pressure (goal of less than 120 mmHg) versus standard lowering (goal of less than 140 mmHg) upon cardiovascular, renal, and safety outcomes differed by gender. METHODS: Nine thousand three hundred and sixty-one men and women aged 50 years or older with systolic blood pressure of 130 mmHg or greater, taking 0-4 antihypertensive medications, and with increased risk of cardiovascular disease, but free of diabetes, were randomly assigned to either a systolic blood pressure target of less than 120 mmHg (intensive treatment) or a target of less than 140 mmHg (standard treatment). The primary composite outcome encompassed incident myocardial infarction, heart failure, other acute coronary syndromes, stroke, or cardiovascular-related death. All-cause mortality, renal outcomes, and serious adverse events were also assessed. RESULTS: Compared with the standard treatment group, the primary composite outcome in the intensive treatment group was reduced by 16% [hazard ratio 0.84 (0.61-1.13)] in women, and by 27% in men [hazard ratio 0.73 (0.59-0.89), P value for interaction between treatment and gender is 0.45]. Similarly, the effect of the intensive treatment on individual components of the primary composite outcome, renal outcomes, and overall serious adverse events was not significantly different according to gender. CONCLUSION: In adults with hypertension but not with diabetes, treatment to a systolic blood pressure goal of less than 120 mmHg, compared with a goal of less than 140 mmHg, resulted in no heterogeneity of effect between men and women on cardiovascular or renal outcomes, or on rates of serious adverse events.ClinicalTrials.gov number, NCT01206062.

Accountability: a missing construct in models of adherence behavior and in clinical practice.

Piano lessons, weekly laboratory meetings, and visits to health care providers have in common an accountability that encourages people to follow a specified course of action. The accountability inherent in the social interaction between a patient and a health care provider affects patients' motivation to adhere to treatment. Nevertheless, accountability is a concept not found in adherence models, and is rarely employed in typical medical practice, where patients may be prescribed a treatment and not seen again until a return appointment 8-12 weeks later. The purpose of this paper is to describe the concept of accountability and to incorporate accountability into an existing adherence model framework. Based on the Self-Determination Theory, accountability can be considered in a spectrum from a paternalistic use of duress to comply with instructions (controlled accountability) to patients' autonomous internal desire to please a respected health care provider (autonomous accountability), the latter expected to best enhance long-term adherence behavior. Existing adherence models were reviewed with a panel of experts, and an accountability construct was incorporated into a modified version of Bandura's Social Cognitive Theory. Defining accountability and incorporating it into an adherence model will facilitate the development of measures of accountability as well as the testing and refinement of adherence interventions that make use of this critical determinant of human behavior.

Sentinel node biopsy after primary chemotherapy in cT2 N0/1 breast cancer patients: Long-term results of a retrospective study.

BACKGROUND: It is controversial whether sentinel node biopsy (SNB) is adequate in breast cancer patients who become cN0 after primary chemotherapy. To address this we retrospectively compared outcomes in T2 cases given primary chemotherapy, comparing those given axillary dissection (AD) with those given SNB but no AD if sentinel nodes were clinically negative post-chemotherapy. METHODS: We examined overall survival (OS), disease-free survival (DFS), and axillary failure in 317 consecutive cT2 cN0/1 patients given primary chemotherapy followed by quadrantectomy/mastectomy, between January 2002 and December 2007. The approach to the axilla changed over time allowing division into three groups: 101 (31.9%) given upfront AD; 139 (43.8%) given SNB + AD; and 77 (24.3%) given SNB only because the SNs were negative. RESULTS: After median follow-ups of 92 (AD), 99 (SNB + AD) and 72 months (SNB-only), OS (p = 0.131) and DFS (p = 0.087) did not differ between the 3 groups, or between SNB-only and the ypN1 and ypN0 subgroups of SNB + AD, or between the cN0 and cN1 subgroups (before chemotherapy) of the SNB-only group. No SNB-only patient had axillary failure. OS (p = 0.004) and DFS (p = 0.002) were better in patients with complete response than those with partial response or stable/progressive disease. CONCLUSIONS: SNB is adequate in T2 patients who are cN0 after primary chemotherapy, irrespective of axillary status before. Better outcomes after complete pathological remission confirm the prognostic importance of response to primary chemotherapy, and suggest that all T2 patients should receive primary chemotherapy.

Clinical Outcomes by Race and Ethnicity in the Systolic Blood Pressure Intervention Trial (SPRINT): A Randomized Clinical Trial.

BACKGROUND: The Systolic Blood Pressure Intervention Trial (SPRINT) showed that targeting a systolic blood pressure (SBP) of ≤ 120 mm Hg (intensive treatment) reduced cardiovascular disease (CVD) events compared to SBP of ≤ 140 mm Hg (standard treatment); however, it is unclear if this effect is similar in all racial/ethnic groups. METHODS: We analyzed SPRINT data within non-Hispanic White (NHW), non-Hispanic Black (NHB), and Hispanic subgroups to address this question. High-risk nondiabetic hypertensive patients (N = 9,361; 30% NHB; 11% Hispanic) 50 years and older were randomly assigned to intensive or standard treatment. Primary outcome was a composite of the first occurrence of a myocardial infarction, acute coronary syndrome, stroke, decompensated heart failure, or CVD death. RESULTS: Average postbaseline SBP was similar among NHW, NHB, and Hispanics in both treatment arms. Hazard ratios (HRs) (95% confidence interval) (intensive vs. standard treatment groups) for primary outcome were 0.70 (0.57-0.86), 0.71 (0.51-0.98), 0.62 (0.33-1.15) (interaction P value = 0.85) in NHW, NHB, and Hispanics. CVD mortality HRs were 0.49 (0.29-0.81), 0.77 (0.37-1.57), and 0.17 (0.01-1.08). All-cause mortality HRs were 0.61 (0.47-0.80), 0.92 (0.63-1.35), and 1.58 (0.73-3.62), respectively. A test for differences among racial/ethnic groups in the effect of treatment assignment on all-cause mortality was not significant (Hommel-adjusted P value = 0.062) after adjustment for multiple comparisons. CONCLUSION: Targeting a SBP goal of ≤ 120 mm Hg compared to ≤ 140 mm Hg led to similar SBP control and was associated with similar benefits and risks among all racial ethnic groups, though NHBs required an average of ~0.3 more medications. CLINICAL TRIALS REGISTRATION: Trial Number NCT01206062, ClinicalTrials.gov Identifier at https://clinicaltrials.gov/ct2/show/NCT01206062.