Mariano J. Rey

Protective Effect of the Bispiperazinedione ICRF-187 against Doxorubicin-Induced Cardiac Toxicity in Women with Advanced Breast Cancer

Studies in animals suggest that the bispiperazinedione ICRF-187 can prevent the development of dose-related doxorubicin-induced cardiac toxicity. In a randomized trial in 92 women with advanced breast cancer, we compared treatment with fluorouracil, doxorubicin, and cyclophosphamide (FDC), given every 21 days, with the same regimen preceded by administration of ICRF-187 (FDC + ICRF-187). Patients were withdrawn from the study when cardiac toxicity developed or the cancer progressed. The mean cumulative dose of doxorubicin tolerated by patients withdrawn from study was 397.2 mg per square meter of body-surface area in the FDC group and 466.3 mg in the FDC + ICRF-187 group (no significant difference). Eleven patients on the FDC + ICRF-187 arm received cumulative doxorubicin doses above 600 mg per square meter, whereas one receiving FDC was able to remain in the study beyond this dose. Antitumor response rates were similar (FDC vs. FDC + ICRF-187, 3 vs. 4 complete responses; 17 vs. 17 partial responses; and 9.3 vs. 10.3 months to disease progression). Although myelosuppression was slightly greater in the FDC + ICRF-187 group, the incidence of fever, infections, alopecia, nausea and vomiting, or death due to toxicity did not differ between the groups. Cardiac toxicity was evaluated by clinical examination, determination of the left ventricular ejection fraction by multigated nuclear scans, and endomyocardial biopsy. In comparisons of the FDC group with the FDC + ICRF-187 group, clinical congestive heart failure was observed in 11 as compared with 2 patients; the mean decrease in the left ventricular ejection fraction was 7 vs. 1 percent when the cumulative dose of doxorubicin was 250 to 399 mg per square meter (P = 0.02), 16 vs. 1 percent at 400 to 499 mg (P = 0.001), and 16 vs. 3 percent at 500 to 599 mg (P = 0.003); and the Billingham biopsy score was 2 or more in 5 of 13 patients undergoing biopsy vs. none of 13 (P = 0.03). We conclude that ICRF-187 offers significant protection against cardiac toxicity caused by doxorubicin, without affecting the antitumor effect of doxorubicin or the incidence of noncardiac toxic reactions.

ICRF-187 Permits Longer Treatment With Doxorubicin in Women With Breast Cancer

PURPOSE To test potential protection by ICRF-187 against cumulative doxorubicin-dose-related cardiac toxicity, we conducted a randomized clinical trial in 150 women with advanced breast cancer. PATIENTS AND METHODS Patients received fluorouracil (5FU) 500 mg/m2, doxorubicin 50 mg/m2, and cyclophosphamide 500 mg/m2 every 21 days intravenously (IV) (control regimen, 74 patients), or the same regimen preceded by ICRF-187 1,000 mg/m2 IV (experimental regimen, 76 patients). RESULTS We previously reported that ICRF-187 in this dose and schedule provides cardiac protection and does not substantially alter the noncardiac toxicity or antitumor efficacy of the control regimen. In this updated analysis of the entire patient cohort, we provide additional support for these findings and demonstrate that patients in the ICRF-187 group received more cycles (median, 11) and higher cumulative doses (median, 500 mg/m2) of doxorubicin than patients in the control group (median, nine cycles, P less than .01; and 441 mg/m2, P less than .05). Twenty-six patients in the ICRF-187 group received doxorubicin doses of at least 700 mg/m2, and among them, 11 patients received 1,000 mg/m2 or more. Only three patients in the control group received doxorubicin doses of 700 mg/m2; the maximum dose administered to one patient in this group was 950 mg/m2. ICRF-187 cardiac protection was demonstrated by difference in incidence of clinical congestive heart failure (CHF; two patients in the ICRF-187 group v 20 in the control group; P less than .0001) and by differences in resting left ventricular ejection fraction (LVEF) determined by multigated radionuclide (MUGA) scan from baselines and that required patient removal from study (five patients in the ICRF-187 group had a decrease in LVEF to less than 0.45 or a decrease from the baseline LVEF of 0.20 or more v 32 in the control group; P less than .000001). Among the 30 patients who had an assessable endomyocardial biopsy at cumulative doxorubicin 450 mg/m2, none of 16 in the ICRF-187 group and six of 14 in the control group had a score of 2 (P less than .05). ICRF-187 cardiac protection was observed in patients with and without prior chest-wall radiation or other risk factors for developing doxorubicin cardiac toxicity. CONCLUSION By protecting against cumulative doxorubicin-induced cardiac toxicity, ICRF-187 permits significantly greater doses of doxorubicin to be administered to patients with greater safety.

Effects of intracoronary streptokinase and intracoronary nitroglycerin infusion on coronary angiographic patterns and mortality in patients with acute myocardial infarction

We randomly assigned patients with a clinical diagnosis of acute myocardial infarction to one of four treatment groups: intracoronary streptokinase, intracoronary nitroglycerin, intracoronary streptokinase and intracoronary nitroglycerin, or conventional therapy without initial angiography. Of 124 patients 122 sustained acute myocardial infarction. Initial angiography revealed total occlusion of the coronary artery responsible for infarction in 67 per cent (61 of 91). Acute recanalization occurred in 74 per cent (32 of 43) of patients receiving streptokinase but in only 6 per cent (1 of 18) of patients treated with nitroglycerin alone (P less than 0.01). At angiography of all four groups on Day 10 to 14 the vessel responsible for acute myocardial infarction was patent in 77 per cent (71 of 92) of patients; there was no difference among groups, indicating gradual, endogenous thrombolysis in patients not treated with streptokinase. Patients with subtotal obstruction initially had significant improvement in left ventricular function, significantly lower peak creatine kinase levels, and a trend toward lower mortality than patients with total occlusion initially. Mortality at six months in patients receiving streptokinase (21 per cent, 13 of 62) did not differ significantly from that in patients not treated with streptokinase (10 per cent, 6 of 61). Additional studies will be necessary to assess treatment effects in the angiographic subsets identified by this trial.

Late thrombolytic therapy preserves left ventricular function in patients with collateralized total coronary occlusion: primary end point findings of the second Mount Sinai-New York University reperfusion trial

The change in left ventricular ejection fraction from preintervention to predischarge was prospectively assessed in 393 patients with acute myocardial infarction. Within 12 h of symptom onset (mean 6.3 +/- 2.7 h), patients were randomly assigned to a double-blind intracoronary infusion of streptokinase, nitroglycerin, both streptokinase and nitroglycerin or conventional therapy without acute cardiac catheterization. Treatment effects were also assessed in prospectively defined angiographic subsets. There was a significant interaction between streptokinase and nitroglycerin (p less than 0.01), resulting in an increase in ejection fraction of 3.9 percentage units in the combined treatment arm (p less than 0.001). Patients with collateral flow to a totally obstructed infarct-related artery showed a significant improvement over those without collateral flow in the streptokinase (5.4 +/- 2.5%) and streptokinase-nitroglycerin (10.6 +/- 2.7%) arms, but not in the nitroglycerin arm. Time to treatment did not influence the change in ejection fraction. In patients with initial subtotal occlusion, thrombolytic therapy was of no short-term benefit because ejection fraction increased by 6% in all three intervention arms. These findings indicate that relatively late thrombolytic therapy results in significant myocardial salvage in those patients with collateralized total coronary occlusion. This benefit is potentiated by concomitant nitroglycerin therapy.

Effects of horticultural therapy on mood and heart rate in patients participating in an inpatient cardiopulmonary rehabilitation program.

PURPOSE To assess the effects of horticultural therapy (HT) on mood state and heart rate (HR) in patients participating in an inpatient cardiac rehabilitation program. METHODS Cardiac rehabilitation inpatients (n = 107) participated in the study. The HT group consisted of 59 subjects (34 males, 25 females). The control group, which participated in patient education classes (PECs), consisted of 48 subjects (31 males, 17 females). Both HT sessions and PEC are components of the inpatient rehabilitation program. Each group was evaluated before and after a class in their respective modality. Evaluation consisted of the completion of a Profile of Mood States (POMS) inventory, and an HR obtained by pulse oximetry. RESULTS Changes in the POMS total mood disturbance (TMD) score and HR between preintervention and postintervention were compared between groups. There was no presession difference in either TMD score (16 +/- 3.6 and 19.0 +/- 3.2, PEC and HT, respectively) or HR (73.5 +/- 2.5 and 79 +/- 1.8, PEC and HT, respectively). Immediately following the intervention, the HT TMD was significantly reduced (post-TMD = 1.6 +/- 3.2, P < .001), while PEC TMD was not significantly changed (TMD = 17.0 +/- 28.5). After intervention, HR fell in HT by 4 +/- 9.6 bpm (P < .001) but was unchanged in PEC. CONCLUSION These findings indicate that HT improves mood state, suggesting that it may be a useful tool in reducing stress. Therefore, to the extent that stress contributes to coronary heart disease, these findings support the role of HT as an effective component of cardiac rehabilitation.

Smoking Among Asian Americans: Acculturation and Gender in the Context of Tobacco Control Policies in New York City

New York City (NYC) has experienced significant decline in smoking prevalence since its antismoking campaign; however, the rates among NYC’s Asian communities have persisted since 2002. Using combined data from the REACH US Risk Factor Survey (2009-2011), this article examined ethnic- and gender-specific smoking behaviors and the effects of acculturation and location of residence on cigarette smoking behavior among Chinese, Korean, Asian Indians, and other Asian Americans. Results indicated that current smoking prevalence was higher for men than women among all four groups. Korean men and women had the highest current smoking rates whereas Indians had the lowest among the four subgroups. Asian American women reporting speaking only English at home had higher current smoking prevalence, but this was not observed for men. Living in Sunset Park, an emerging Asian ethnic enclave, was associated with higher odds of smoking than living in other locations in NYC. In conclusion, smoking prevalence varied across gender and ethnic subgroups among Asian Americans in NYC. A “one-size-fits-all” type of intervention strategy for “pan-Asians” could not be effective. Community-based culturally appropriate and gender-specific interventions for smoking cessation might be an option for Asian Americans residing in linguistically isolated ethnic enclaves.

Evaluation of a Community Health Worker Pilot Intervention to Improve Diabetes Management in Bangladeshi Immigrants with Type 2 Diabetes in New York City

Purpose The purpose of this study is to explore the impact and feasibility of a pilot Community Health Worker (CHW) intervention to improve diabetes management among Bangladeshi-American individuals with type 2 diabetes living in New York City. Methods Participants were recruited at clinic- and community-based venues. The intervention consisted of 6 monthly, CHW-facilitated group sessions on topics related to management of diabetes. Surveys were collected at baseline and follow-up time points. Study outcomes included clinical, behavioral, and satisfaction measures for participants, as well as qualitative measures from CHWs. Results Improvements were seen in diabetes knowledge, exercise and diet to control diabetes, frequency of checking feet, medication compliance, and self-efficacy of health and physical activity from baseline to 12 months. Additionally, there were decreases in A1C, weight, and body mass index. Program evaluation revealed a high acceptability of the intervention, and qualitative findings indicated that CHWs helped overcome barriers and facilitated program outcomes through communal concordance, trust, and leadership. Conclusions The intervention demonstrated high acceptability and suggested efficacy in improving diabetes management outcomes among Bangladeshi immigrants in an urban setting. The US Bangladeshi population will continue to increase, and given the high rates of diabetes, as well as linguistic and economic barriers faced by this community, effective and culturally tailored health interventions are needed to overcome barriers and provide support for diabetes management.

The asian american hepatitis B program: building a coalition to address hepatitis B health disparities.

Background: Community coalitions are increasingly recognized as important strategies for addressing health disparities. By providing the opportunity to pool resources, they provide a means to develop and sustain innovative approaches to affect community health. Objectives: This article describes the challenges and lessons learned in building the Asian American Hepatitis B Program (AAHBP) coalition to conduct a community-based participatory research (CBPR) initiative to address hepatitis B (HBV) among New York City Asian-American communities. Methods: Using the stages of coalition development as a framework, a comprehensive assessment of the process of developing and implementing the AAHBP coalition is presented. Lessons Learned: Findings highlight the importance of developing a sound infrastructure and set of processes to foster a greater sense of ownership, shared vision, and investment in the program. Conclusion: Grassroots community organizing and campus–community partnerships can be successfully leveraged to address and prevent a significant health disparity in an underserved and diverse community.

Protocol for the DREAM Project (Diabetes Research, Education, and Action for Minorities): a randomized trial of a community health worker intervention to improve diabetic management and control among Bangladeshi adults in NYC.

BackgroundNew York City (NYC) is currently home to the largest Bangladeshi population in the United States (US) at approximately 62,000 individuals. The high prevalence of Type 2 diabetes mellitus (T2DM) among Bangladeshis has been well documented in Bangladesh, as well as in Canada and the United Kingdom (UK). However, little is known about the diabetes prevalence and management practices of US Bangladeshis. This paper describes the protocol for a Community Health Worker (CHW) intervention to improve diabetic management and control among Bangladeshis with diabetes in NYC.Methods/DesignFor a two-arm, randomized controlled trial (RCT), investigators will recruit a sample of 256 participants, all of whom are 1) of Bangladeshi descent, 2) residing in NYC, 3) diagnosed with T2DM and a recent Hemoglobin A1c (HbA1c) of ≥ 6.5, and 4) between the ages of 21–85. The treatment group receives a six-month CHW-led intervention consisting of five monthly group educational sessions, two one-on-one visits, and follow-up phone calls as needed from a CHW. The control group receives an introductory educational session only. Primary and secondary outcomes include clinical and behavioral measures, such as HbA1c and weight change, access to and utilization of care (i.e. appointment keeping and use of specialty care), and knowledge and practice of physical activity and healthful eating. Additionally, information regarding CHW characteristics, the processes and mechanisms for influencing healthful behavior change, and fidelity of the intervention are collected. Outcomes are measured at Baseline, 3-Months, 6-Months for both groups, and at 12-Months for the treatment group.DiscussionTo our knowledge, this study represents the first attempt to document the efficacy of T2DM management strategies in the NYC Bangladeshi population. Thus, future qualitative and quantitative findings of the submitted protocol will fill an important gap in the health disparities literature.Trial registrationNCT02041598

Understanding Barriers to and Facilitators of Diabetes Control and Prevention in the New York City Bangladeshi Community: A Mixed-Methods Approach

We have reported results from the formative stage of a community health worker intervention designed to improve diabetes management among Bangladeshi patients in New York City. Trained community health workers conducted focus groups (n = 47) and surveys (n = 169) with Bangladeshi individuals recruited from community locations. Results indicated that participants faced numerous barriers to care, had high rates of limited English proficiency, and had low levels of knowledge about diabetes. Most participants expressed interest in participating in a community health worker intervention.