The planned number of programs was delivered, but the proportion of study-eligible attendees was lower than predicted. This community-based participatory research approach was largely successful in involving the community served in the development and implementation of the intervention and study.
ObjectivesThe HIV epidemic in India is concentrated in key populations such as people who inject drugs (PWID). New HIV infections are high among young PWID (≤30 years of age), who are hard to engage in services. We assessed perspectives of young PWID to guide development of youth-specific services.SettingWe conducted focus group discussions (FGDs) with PWID and staff at venues offering services to PWID in three Indian cities representing historical and emerging drug use epidemics.ParticipantsPWID were eligible to participate if they were between 18 and 35 years, had initiated injection as adolescents or young adults and knew adolescent PWID in their networks. 43 PWID (81% male, 19% female) and 10 staff members participated in FGDs. A semistructured interview guide was used to elicit participants’ narratives on injection initiation experiences, barriers to seeking harm reduction services, service delivery gaps and recommendations to promote engagement. Thematic analysis was used to develop an explanatory model for service engagement in each temporal stage across the injection continuum.ResultsInjection initiation followed non-injection opioid dependence. Lack of services for non-injection opioid dependence was a key gap in the preinjection initiation phase. Lack of knowledge and reliance on informal sources for injecting equipment were key reasons for non-engagement in the peri-injection phase. Additionally, low-risk perception resulted in low motivation to seek services. Psychosocial and structural factors shaped engagement after established injection. Housing and food insecurity, and stigma disproportionately affected female PWID while lack of confidential adolescent friendly services impeded engagement by adolescent PWID.ConclusionsDevelopment of youth-specific services for young PWID in India will need to address unique vulnerabilities and service gaps along each stage of the injection continuum. Scaling-up of tailored services is needed for young female PWID and adolescents, including interventions that prevent injection initiation and provision of confidential harm reduction services.
Introduction: The HIV epidemic in India is concentrated in key populations such as people who inject drugs (PWID). New HIV infections are high among young PWID (<=30 years of age), who are hard to engage in services. We assessed perspectives of young PWID across three Indian cities representing historic and emerging drug use epidemics to guide development of youth-specific services. Methods: We conducted focus group discussions (FGDs) with PWID (ages 18-35 years) and staff at venues offering services to PWID in three cities (Aizawl and Imphal, Northeast India and Amritsar, Northwest India). A semi-structured interview guide was used to elicit participants narratives on injection initiation experiences, motivating factors and barriers to seeking harm-reduction services, service-delivery gaps, and recommendations to promote engagement. Thematic analysis was used to develop an explanatory model for engagement for each temporal stage across the injection continuum: (a) pre-injection initiation, (b) peri-injection initiation and (c) established injection behavior. Results: 43 PWID (81% male, 19% female) and 10 staff members participated in FGDs. Injection initiation followed non-injection opioid dependence. Lack of services for non-injection opioid dependence was a key gap in the pre-injection initiation phase. Lack of knowledge and reliance on informal sources for injecting equipment were key reasons for non-engagement in the peri-injection phase. Additionally, low risk perception resulted in low motivation to seek services. Psychosocial and structural factors shaped engagement after established injection. Housing and food insecurity, and stigma disproportionately affected female PWID while lack of confidential adolescent friendly services impeded engagement by adolescent PWID. Conclusions: Development of youth-specific services for young PWID in India will need to address unique vulnerabilities and service gaps along each stage of the injection continuum. Scaling-up of tailored services is needed for young female PWID and adolescents, including interventions that prevent injection initiation and provision of confidential harm-reduction services.
Introduction: Work in cancer biology, epidemiology and preclinical models has made it clear that non-steroidal anti-inflammatory drugs (NSAIDs) in general and aspirin in particular can significantly affect the development of several types of cancer, with colon cancer representing the best-studied case. However, NSAIDs have significant side effects that precludes there wide spread use. Notably, there are no chemotherapeutic applications for NSAIDs in humans or animals. In our search for a better NSAID, we developed NOSH-aspirin, a hybrid molecule that releases nitric oxide (NO) and hydrogen sulfide (H2S), two gasotransmitters of physiological relevance. Previously, we reported on the anti-inflammatory properties of NOSH-aspirin and showed that it was in the order of 100,000 to 250,000-fold more potent than aspirin in inhibiting colon cancer cell growth over a 24-72h-time period with negligible cyto-toxicity. Here we report on the effects of NOSH-aspirin alone and in combination with 5-fluorouracil (5-FU) on treatment of established tumors in a xenograft model of human colon cancer. Methods: NOSH-aspirin was synthesized and purified by us. Cell line: HT-29 human adenocarcimoma. Xenografts: Female nude mice (N=20) were implanted s.c. in the right flank with HT-29 (2 x 106) cells; when the tumor volumes reached 60-80 mm3, the animals were randomly divided into 4 groups (N=5/gp) and treated with NOSH-aspirin (po,100 mg/kg body wt/day), 5-FU (ip, 10 mg/kg x 2/week), NOSH-aspirin+5-FU as above, or vehicle (po). Tumor volume and animal weight were recorded every 3 days. After 3 weeks of treatment, mice were sacrificed, tumors excised, weighed, and fixed in 10% buffered formalin for IHC studies. We also weighed the livers and the kidneys. Results: In vitro, NOSH-aspirin and 5-FU inhibited the growth of HT-29 cells with IC50s of 48±3 and 20,000±2000 nM at 24 hr, respectively. In presence of 5-FU at 0.25x, 0.5x, and 1x it's IC50, the IC50s for NOSH-aspirin was reduced to 31±3, 15.5±2, and 0.75±0.2 nM, respectively. In vivo: NOSH-aspirin reduced tumor volume more than 5-FU as a function of time; however, the biggest reduction in tumor volume was in the combination group. Tumor mass at sacrifice in each group was, vehicle (3.2±0.62g), NOSH-aspirin (0.54±0.18g, 83% reduction, P<0.005), 5-FU (1.17±0.37g, 63% reduction, P<0.01), NOSH-aspirin+5-FU (0.17±0.056g reduction 87% reduction P<0.001). NOSH-aspirin had no effect on the weight of the mice whether alone or in combination with 5-FU, there were no overt signs of toxicity. There was a 10% reduction in the weight of animals in the 5-FU group, however, this difference was not statistically significant. There were no differences in liver or kidney masses amongst the groups. Conclusions: NOSH-aspirin has potent anti-cancer properties and demonstrates synergistic properties with 5-FU. It merits further evaluation as a chemotherapeutic agent. Citation Format: Clarissa J. Martinez, Mitali Chattopadhyay, Khosrow Kashfi. NOSH-aspirin and 5-fluorouracil demonstrate synergistic efficacy in a xenograft model of colon cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 793. doi:10.1158/1538-7445.AM2014-793
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