Assessing Health Disparities in Rural Hawaii Using the Hoshin Facilitation Method

CONTEXT: Health disparities between rural and urban communities are well documented. There are many suggested causes and many proposed solutions but no one-size-fits-all answer. The most successful community interventions have been introduced by communities themselves. However, before communities invest in such interventions, each group must identify and prioritize their needs. PURPOSE: This article describes the Hoshin facilitation method as a practical option assisting communities in assessing their needs and gaining consensus for future steps. METHODS: Thirty-four meetings were held in 11 rural communities in Hawaii using the Hoshin process to identify factors that impact rural health. Themes were identified by constant comparative analysis and thematic frequency described. Commonality of responses between communities was examined. Informal feedback was collected from meeting participants. FINDINGS: There was a great deal of commonality between community responses, with economic factors, drug use, lack of community leadership, lack of health care services and access to services, lack of healthy activities for youth, and poor public education being the most common issues noted. Group involvement in the meetings was high, and the facilitation method received positive feedback from participants. CONCLUSIONS: The Hoshin facilitation method is a very useful tool to help communities rapidly identify and prioritize areas for programmatic attention.     

Application of Screening Methods,Shape Signatures and Engineered Biosensors in Early Drug Discovery Process

Purpose  

In this study, two unreported estrogen antagonists were identified using a combination of computational screening and a simple bacterial estrogen sensor.     

Volumetric shrinkage of composites using video-imaging

Objective. This study involves investigation of the use of video-imaging for measurement of volumetric shrinkage of composites.Methods. Six composites were tested for volumetric shrinkage using video-imaging. The volumetric shrinkage was measured using the single- and multi-view volumetric reconstruction modes. All composites were cured using a VIP(TM) curing light for 40s at 500mW/cm(2). Dynamic shrinkage was measured using the single-view mode with a red filter placed over the detector opening.Results. Analysis of the volumetric shrinkage values by a one way ANOVA for each composite showed no difference for the single- and multi-view measurement mode. The shrinkage values determined by video-imaging were compared to those measured for the same composites by mercury dilatometry by one way ANOVA followed by a paired comparison using the Bonferroni method.Conclusion. The video-imaging technique gives reproducible results for volumetric shrinkage of composites comparable to those measured by dilatometry.     

Uterine serous carcinoma: increased familial risk for lynch-associated malignancies

Serous uterine cancer is not a feature of any known hereditary cancer syndrome. This study evaluated familial risk of cancers for patients with serous uterine carcinoma, focusing on Lynch syndrome malignancies. Fifty serous or mixed serous endometrial carcinoma cases were prospectively enrolled. Pedigrees were developed for 29 probands and tumors were assessed for DNA mismatch repair (MMR) abnormalities. Standardized incidence ratios for cancers in relatives were estimated. A second-stage analysis was undertaken using data from Gynecologic Oncology Group (GOG)-210. Incidence data for cancers reported in relatives of 348 patients with serous and mixed epithelial and 624 patients with endometrioid carcinoma were compared. Nineteen of 29 (65.5%) patients in the single-institution series reported a Lynch-related cancer in relatives. Endometrial and ovarian cancers were significantly overrepresented and a high number of probands (6 of 29, 20.7%) reported pancreatic cancers. None of the probands' tumors had DNA MMR abnormalities. There was no difference in endometrial or ovarian cancer incidence in relatives of serous and endometrioid cancer probands in the case-control study. Pancreatic cancers were, however, significantly more common in relatives of patients with serous cancer [OR, 2.39; 95% confidence interval (CI), 1.06-5.38]. We identified an excess of endometrial, ovarian, and pancreatic cancers in relatives of patients with serous cancer in a single-institution study. Follow-up studies suggest that only pancreatic cancers are overrepresented in relatives. DNA MMR defects in familial clustering of pancreatic and other Lynch-associated malignancies are unlikely. The excess of pancreatic cancers in relatives may reflect an as yet unidentified hereditary syndrome that includes uterine serous cancers.     

The Diarylquinoline R207910 Is Bactericidal against Mycobacterium leprae in Mice at Low Dose and Administered Intermittently

The diarylquinoline R207910 is profoundly bactericidal in a murine model of tuberculosis. Previously, R207910 was also found to be bactericidal for Mycobacterium leprae-infected mice during lag phase. Herein we evaluate the bactericidal efficacy of R207910 (1 to 120 mg/kg of body weight) when administered five times weekly, once weekly, and once monthly during logarithmic multiplication of M. leprae organisms. All treatments were found to be bactericidal, suggesting that both low and intermittent dosing with R207910 holds promise for leprosy patients.The diarylquinoline R207910 (also known as TMC207) represents a new class of antimicrobials uniquely active against mycobacteria, killing mycobacteria in vitro by blocking energy production (1). In vitro, R207910 has been found to inhibit a wide range of Mycobacterium tuberculosis clinical isolates and other mycobacterial species (1). In murine tuberculosis, daily administration of R207910 alone exceeds the bactericidal activity of the standard WHO regimen (isoniazid, rifampin [rifampicin], and pyrazinamide) (1). Also a combination with rifapentine and pyrazinamide given once weekly proved to be more active than the daily regimen recommended by the WHO (22). R207910 has several virtues that heighten its promise for the therapy of tuberculosis, such as a low MIC and a low minimal bactericidal concentration (1), demonstrable activity against nonreplicating M. tuberculosis organisms (15), and a prolonged plasma half-life in human volunteers (1).Previously, Ji et al. (14) demonstrated that single doses of 25 mg/kg of body weight or 100 mg/kg given 1 day after infection of mice with Mycobacterium leprae (i.e., during lag phase) were equally bactericidal and that the bactericidal activity was equipotent to those of rifampin, rifapentine, and moxifloxacin while being superior to those of minocycline, PA-824, and linezolid. In order to further evaluate the activity of R207910 and assess different doses and frequencies of administration, we initiated a dose fractionation study wherein the activity of R207910 against M. leprae in infected mice was evaluated by a different technique, the standard kinetic method of Shepard (19). In this protocol, CBA/J mice were infected in both hind footpads with 5,000 M. leprae organisms and orally treated by gavage during logarithmic multiplication from day 60 to day 150 after infection with several dosage schedules of R207910, formulated in 20% hydroxypropyl-ß-cyclodextrin.Study mice were (i) untreated (controls); (ii) treated five times weekly with 1 mg/kg, 3 mg/kg, 6 mg/kg, 12.5 mg/kg, and 25 mg/kg for 3 months; (iii) treated once weekly with 25 mg/kg, 30 mg/kg, 50 mg/kg, and 100 mg/kg for 3 months; and (iv) treated once monthly with 25 mg/kg, 50 mg/kg, 100 mg/kg, and 120 mg/kg (three doses). Keeping in mind that for murine tuberculosis the total weekly dosage has been shown to be the driver of activity, irrespective of the frequency of administration (22), we specifically designed several dosage schedules to deliver the same monthly dose of R207910. M. leprae organisms were enumerated in hind footpad pools (two mice, four feet) at the completion of therapy (day 152) and 3 months later (day 238), as well as on days 302 to 363 for some groups. With the kinetic method, if ≥10⁵ M. leprae organisms are obtained, growth is considered to have occurred. If growth is obtained at the completion of therapy, the treatment is considered to be inactive. If growth of M. leprae is not obtained at completion of therapy but is soon thereafter, activity is considered bacteriostatic, and if growth is further suppressed, bactericidal activity is considered to have occurred (19).In all control mice, M. leprae growth (≥10⁵ organisms per footpad) was confirmed on day 152 (completion of therapy) and reached levels greater than 10⁶ organisms on days 228 and 338 (Table ​(Table1).1). On the other hand, growth was not found in any of the mice treated with any dosage of R207910, either on day 152 or on day 228, a result demonstrating that all dosage schedules were bactericidal for M. leprae. Furthermore, evidence for prolonged prevention of multiplication and for the bactericidal activity of R207910 (as assessed on days 302 to 363) was obtained for several groups treated once weekly and once monthly. Five weekly doses of R207910 as low as 1 mg/kg (approximately 25 mg/kg per month) were found to be as bactericidal for M. leprae as a single monthly dose of 25 mg/kg.

TABLE 1.

Multiplication of M. leprae organisms in mice

Social Justice in Medical Education: Strengths and Challenges of a Student-Driven Social Justice Curriculum

In the current rapidly evolving healthcare environment of the United States, social justice programs in pre-medical and medical education are needed to cultivate socially conscious and health professionals inclined to interdisciplinary collaborations. To address ongoing healthcare inequalities, medical education must help medical students to become physicians skilled not only in the biomedical management of diseases, but also in identifying and addressing social and structural determinants of the patients'' daily lives. Using a longitudinal Problem-Based Learning (PBL) methodology, the medical students and faculty advisers at the University of Hawai‘i John A. Burns School of Medicine (JABSOM) developed the Social Justice Curriculum Program (SJCP) to supplement the biomedical curriculum. The SJCP consists of three components: (1) active self-directed learning and didactics, (2) implementation and action, and (3) self-reflection and personal growth. The purpose of introducing a student-driven SJ curriculum is to expose the students to various components of SJ in health and medicine, and maximize engagement by using their own inputs for content and design. It is our hope that the SJCP will serve as a logistic and research-oriented model for future student-driven SJ programs that respond to global health inequalities by cultivating skills and interest in leadership and community service.