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"Go upstream, young man": lessons learned from the p38 saga.

ABSTRACT: Despite the success of biological therapies in rheumatoid arthritis (RA), orally active small-molecule drugs are desirable. Signal transduction inhibitors have been the focus of intense efforts, with some recent notable successes and failures. p38alpha is a signalling molecule that regulates proinflammatory cytokines, which makes it a logical target for RA. Unfortunately, selective p38alpha inhibitors have limited efficacy. An attempt is made here to put these studies into perspective and offer possible explanations for the failure of p38alpha blockers. Alternative strategies, such as targeting kinases higher in the signalling cascade or using less selective compounds, might be more successful as suggested by the efficacy seen with Syk and JAK inhibitors.

SUBMITTER: Hammaker D

PROVIDER: S-EPMC2911016 | biostudies-other | 2010 Jan

REPOSITORIES: biostudies-other

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"Go upstream, young man": lessons learned from the p38 saga.

Hammaker D D Firestein G S GS

Annals of the rheumatic diseases 20100101

Despite the success of biological therapies in rheumatoid arthritis (RA), orally active small-molecule drugs are desirable. Signal transduction inhibitors have been the focus of intense efforts, with some recent notable successes and failures. p38alpha is a signalling molecule that regulates proinflammatory cytokines, which makes it a logical target for RA. Unfortunately, selective p38alpha inhibitors have limited efficacy. An attempt is made here to put these studies into perspective and offer ...[more]

PMID: 19995751

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Project description:BackgroundSmoking rates are significantly higher among young people experiencing homelessness than in the general population. Despite a willingness to quit, homeless youth have little success in doing so on their own, and existing cessation resources tailored to this population are lacking. Homeless youth generally enjoy the camaraderie and peer support that group-based programs offer, but continuous in-person support during a quit attempt can be prohibitively expensive.ObjectiveThis study aimed to assess the feasibility and acceptability of an automated text messaging intervention (TMI) as an adjunct to group-based cessation counseling and provision of nicotine patches to help homeless youth quit smoking. This paper outlines the lessons learned from the implementation of the TMI intervention.MethodsHomeless youth smokers aged 18 to 25 years who were interested in quitting (n=77) were recruited from drop-in centers serving homeless youth in the Los Angeles area. In this pilot randomized controlled trial, all participants received a group-based cessation counseling session and nicotine patches, with 52% (40/77) randomly assigned to receive 6 weeks of text messages to provide additional support for their quit attempt. Participants received text messages on their own phone rather than receiving a study-issued phone for the TMI. We analyzed baseline and follow-up survey data as well as back-end data from the messaging platform to gauge the acceptability and feasibility of the TMI among the 40 participants who received it.ResultsParticipants had widespread (smart)phone ownership-16.4% (36/219) were ineligible for study participation because they did not have a phone that could receive text messages. Participants experienced interruptions in their phone use (eg, 44% [16/36] changed phone numbers during the follow-up period) but reported being able to receive the majority of messages. These survey results were corroborated by back-end data (from the program used to administer the TMI) showing a message delivery rate of about 95%. Participant feedback points to the importance of carefully crafting text messages, which led to high (typically above 70%) approval of most text messaging components of the intervention. Qualitative feedback indicated that participants enjoyed the group counseling session that preceded the TMI and suggested including more such group elements into the intervention.ConclusionsThe TMI was well accepted and feasible to support smoking cessation among homeless youth. Given high rates of smartphone ownership, the next generation of phone-based smoking cessation interventions for this population should consider using approaches beyond text messages and focus on finding ways to develop effective approaches to include group interaction using remote implementation. Given overall resource constraints and in particular the exigencies of the currently ongoing COVID-19 epidemic, phone-based interventions are a promising approach to support homeless youth, a population urgently in need of effective smoking cessation interventions.Trial registrationClinicalTrials.gov NCT03874585; https://clinicaltrials.gov/ct2/show/NCT03874585.International registered report identifier (irrid)RR2-10.1186/s13722-020-00187-6.

Project description:Preventing new HIV infections, especially amongst young women, is key to ending the HIV epidemic especially in sub-Saharan Africa. Potent antiretroviral (ARV) drugs used as pre-exposure prophylaxis (PrEP) are currently being formulated as long-acting implantable devices, or nanosuspension injectables that release drug at a sustained rate providing protection from acquiring HIV. PrEP as implants (PrEP Implants) offers an innovative and novel approach, expanding the HIV prevention toolbox. Feedback from providers and future users in the early clinical product development stages may identify modifiable characteristics which can improve acceptability and uptake of new technologies. Healthcare workers (HCWs) perspectives and lessons learned during the rollout of contraceptive implants will allow us to understand what factors may impact the roll-out of PrEP implants. We conducted eighteen interviews with HCWs (9 Nurses and 9 Community Healthcare Workers) in rural KwaZulu-Natal, South Africa. HCWs listed the long-acting nature of the contraceptive implant as a key benefit, helping to overcome healthcare system barriers like heavy workloads and understaffing. However, challenges like side effects, migration of the implant, stakeholder buy-in and inconsistent training on insertion and removal hampered the roll-out of the contraceptive implant. For PrEP implants, HCWs preferred long-acting products that were palpable and biodegradable. Our findings highlighted that the characteristics of PrEP implants that are perceived to be beneficial by HCWs may not align with that of potential users, potentially impacting the acceptability and uptake of PrEP implants. Further our data highlight the need for sustained and multi-pronged approaches to training HCWs and introducing new health technologies into communities. Finding a balance between the needs of HCWs that accommodate their heavy workloads, limited resources at points of delivery of care and the needs and preferences of potential users need to be carefully considered in the development of PrEP implants.

Dataset Information

"Go upstream, young man": lessons learned from the p38 saga.

Publications

"Go upstream, young man": lessons learned from the p38 saga.

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