Safe inhalation pipe provision (SIPP): protocol for a mixed-method evaluation of an intervention to improve health outcomes and service engagement among people who use crack cocaine in England.

BACKGROUND: Over 180,000 people use crack cocaine in England, yet provision of smoking equipment to support safer crack use is prohibited under UK law. Pipes used for crack cocaine smoking are often homemade and/or in short supply, leading to pipe sharing and injuries from use of unsafe materials. This increases risk of viral infection and respiratory harm among a marginalised underserved population. International evaluations suggest crack pipe supply leads to sustained reductions in pipe sharing and use of homemade equipment; increased health risk awareness; improved service access; reduction in injecting and crack-related health problems. In this paper, we introduce the protocol for the NIHR-funded SIPP (Safe inhalation pipe provision) project and discuss implications for impact. METHODS: The SIPP study will develop, implement and evaluate a crack smoking equipment and training intervention to be distributed through peer networks and specialist drug services in England. Study components comprise: (1) peer-network capacity building and co-production; (2) a pre- and post-intervention survey at intervention and non-equivalent control sites; (3) a mixed-method process evaluation; and (4) an economic evaluation. Participant eligibility criteria are use of crack within the past 28 days, with a survey sample of ~ 740 for each impact evaluation survey point and ~ 40 for qualitative process evaluation interviews. Our primary outcome measure is pipe sharing within the past 28 days, with secondary outcomes pertaining to use of homemade pipes, service engagement, injecting practice and acute health harms. ANTICIPATED IMPACT: SIPP aims to reduce crack use risk practices and associated health harms; including through increasing crack harm reduction awareness among service providers and peers. Implementation has only been possible with local police approvals. Our goal is to generate an evidence base to inform review of the legislation prohibiting crack pipe supply in the UK. This holds potential to transform harm reduction service provision and engagement nationally. CONCLUSION: People who smoke crack cocaine in England currently have little reason to engage with harm reduction and drug services. Little is known about this growing population. This study will provide insight into population characteristics, unmet need and the case for legislative reform. TRIAL REGISTRATION: ISRCTN12541454  https://doi.org/10.1186/ISRCTN12541454.

The recombinant Link module of human TSG-6 suppresses cartilage damage in models of osteoarthritis: A potential disease-modifying OA drug.

OBJECTIVE: To investigate the role of endogenous TSG-6 in human osteoarthritis (OA) and assess the disease-modifying potential of a TSG-6-based biological treatment in cell, explant and animal models of OA. DESIGN: Knee articular cartilages from OA patients were analyzed for TSG-6 protein and mRNA expression using immunohistochemistry and RNAscope, respectively. The inhibitory activities of TSG-6 and its isolated Link module (Link_TSG6) on cytokine-induced degradation of OA cartilage explants were compared. Human mesenchymal stem/stromal cell-derived chondrocyte pellet cultures were used to determine the effects of Link_TSG6 and full-length TSG-6 on IL-1α-, IL-1ß-, or TNF-stimulated ADAMTS4, ADAMTS5, and MMP13 mRNA expression. Link_TSG6 was administered i.a. to the rat ACLTpMMx model; cartilage damage and tactile allodynia were assessed. RESULTS: TSG-6 is predominantly associated with chondrocytes in regions of cartilage damage where high TSG-6 expression aligns with low MMP13, the major collagenase implicated in OA progression. Link_TSG6 is more potent than full-length TSG-6 at inhibiting cytokine-mediated matrix breakdown in human OA cartilage explants;>50% of donor cartilages, from 59 tested, were responsive to Link_TSG6 treatment. Link_TSG6 also displayed more potent effects in 3D pellet cultures, suppressing ADAMTS4, ADAMTS5, and MMP13 gene expression, which was consistent with reduced aggrecanase and collagenase activities in explant cultures. Link_TSG6 treatment reduced touch-evoked pain behavior and dose-dependently inhibited cartilage damage in a rodent model of surgically-induced OA. CONCLUSIONS: Link_TSG6 has enhanced chondroprotective activity compared to the full-length TSG-6 protein and shows potential as a disease modifying OA drug via its inhibition of aggrecanase and collagenase activity.

Analysis of the UK Government's 10-Year Drugs Strategy-a resource for practitioners and policymakers.

In 2021, during a drug-related death crisis in the UK, the Government published its ten-year drugs strategy. This article, written in collaboration with the Faculty of Public Health and the Association of Directors of Public Health, assesses whether this Strategy is evidence-based and consistent with international calls to promote public health approaches to drugs, which put 'people, health and human rights at the centre'. Elements of the Strategy are welcome, including the promise of significant funding for drug treatment services, the effects of which will depend on how it is utilized by services and local commissioners and whether it is sustained. However, unevidenced and harmful measures to deter drug use by means of punishment continue to be promoted, which will have deleterious impacts on people who use drugs. An effective public health approach to drugs should tackle population-level risk factors, which may predispose to harmful patterns of drug use, including adverse childhood experiences and socioeconomic deprivation, and institute evidence-based measures to mitigate drug-related harm. This would likely be more effective, and just, than the continuation of policies rooted in enforcement. A more dramatic re-orientation of UK drug policy than that offered by the Strategy is overdue.

Development, acceptability and feasibility of a personalised, behavioural intervention to prevent bacterial skin and soft tissue infections among people who inject drugs: a mixed-methods Person-Based Approach study.

BACKGROUND: Skin and soft tissue infections (SSTI) among people who inject drugs (PWID) are a public health concern. This study aimed to co-produce and assess the acceptability and feasibility of a behavioural intervention to prevent SSTI. METHODS: The Person-Based Approach (PBA) was followed which involves: (i) collating and analysing evidence; (ii) developing guiding principles; (iii) a behavioural analysis; (iv) logic model development; and (v) designing and refining intervention materials. Co-production activities with target group representatives and key collaborators obtained feedback on the intervention which was used to refine its design and content. The intervention, harm reduction advice cards to support conversation between service provider and PWID and resources to support safer injecting practice, was piloted with 13 PWID by four service providers in Bristol and evaluated using a mixed-methods approach. Semi-structured interviews were conducted with 11 PWID and four service providers. Questionnaires completed by all PWID recorded demographic characteristics, SSTI, drug use and treatment history. Interviews were analysed thematically and questionnaires were analysed descriptively. RESULTS: Published literature highlighted structural barriers to safer injecting practices, such as access to hygienic injecting environments and injecting practices associated with SSTI included: limited handwashing/injection-site swabbing and use of too much acidifier to dissolve drugs. Co-production activities and the literature indicated vein care and minimisation of pain as PWID priorities. The importance of service provider-client relationships and non-stigmatising delivery was highlighted through the co-production work. Providing practical resources was identified as important to address environmental constraints to safer injecting practices. Most participants receiving the intervention were White British, male, had a history of SSTI and on average were 43.6 years old and had injected for 22.7 years. The intervention was well-received by PWID and service providers. Intervention content and materials given out to support harm reduction were viewed positively. The intervention appeared to support reflections on and intentions to change injecting behaviours, though barriers to safer injecting practice remained prominent. CONCLUSIONS: The PBA ensured the intervention aligned to the priorities of PWID. It was viewed as acceptable and mostly feasible to PWID and service providers and has transferability promise. Further implementation alongside broader harm reduction interventions is needed.

Barriers to management of opioid withdrawal in hospitals in England: a document analysis of hospital policies on the management of substance dependence.

BACKGROUND: People who use illicit opioids are more likely to be admitted to hospital than people of the same age in the general population. Many admissions end in discharge against medical advice, which is associated with readmission and all-cause mortality. Opioid withdrawal contributes to premature discharge. We sought to understand the barriers to timely provision of opioid substitution therapy (OST), which helps to prevent opioid withdrawal, in acute hospitals in England. METHODS: We requested policies on substance dependence management from 135 National Health Service trusts, which manage acute hospitals in England, and conducted a document content analysis. Additionally, we reviewed an Omitted and Delayed Medicines Tool (ODMT), one resource used to inform critical medicine categorisation in England. We worked closely with people with lived experience of OST and/or illicit opioid use, informed by principles of community-based participatory research. RESULTS: Eighty-six (64%) trusts provided 101 relevant policies. An additional 44 (33%) responded but could not provide relevant policies, and five (4%) did not send a definitive response. Policies illustrate procedural barriers to OST provision, including inconsistent application of national guidelines across trusts. Continuing community OST prescriptions for people admitted in the evening, night-time, or weekend was often precluded by requirements to confirm doses with organisations that were closed during these hours. 42/101 trusts (42%) required or recommended a urine drug test positive for OST medications or opioids prior to OST prescription. The language used in many policies was stigmatising and characterised people who use drugs as untrustworthy. OST was not specifically mentioned in the reviewed ODMT, with 'drugs used in substance dependence' collectively categorised as posing low risk if delayed and moderate risk if omitted. CONCLUSIONS: Many hospitals in England have policies that likely prevent timely and effective OST. This was underpinned by the 'low-risk' categorisation of OST delay in the ODMT. Delays to continuity of OST between community and hospital settings may contribute to inpatient opioid withdrawal and increase the risk of discharge against medical advice. Acute hospitals in England require standardised best practice policies that account for the needs of this patient group.

Pharmacy professionals' views regarding the future of NHS patient medicines helpline services: a multimethod qualitative study.

BACKGROUND: Patient medicines helpline services (PMHS) have been established at some National Health Service (NHS) hospitals, to provide patients with post-discharge medicines-related support. However, findings suggest that many PMHS are provided sub-optimally due to a lack of resources. This study sought to examine pharmacy professionals' perceptions of the future of PMHS. METHODS: Participants comprised pharmacy professionals from NHS Trusts in England that provided a PMHS. Invitations to participate in a qualitative survey and then an interview were sent to pharmacy services at all NHS Trusts that provided a PMHS. This resulted in 100 survey participants and 34 interview participants. Data were analysed using Braun and Clarke's inductive reflexive thematic analysis. RESULTS: Two themes were generated: Enhancing value for service users and Improving efficiency. Enhancing value for service users identifies pharmacy professionals' suggestions for improving the value of PMHS for service users. These include providing access methods extending beyond the telephone, and providing patients/carers with post-discharge follow-up calls from a pharmacist to offer medicines-related support. Improving efficiency identifies that, in the future, and in line with NHS plans for efficiency and shared resources, PMHS may become centralised or provided by community pharmacies. Centralised services were considered to likely have more resources available to provide a patient medicines information service compared to hospital pharmacies. However, such a change was perceived to only increase efficiency if patient information can be shared between relevant healthcare settings. CONCLUSIONS: PMHS are perceived by pharmacy professionals as likely to become centralised in the future (i.e., provided regionally/nationally). However, such change is dependent upon the sharing of patients' information between hospitals and the centralised hub/s or pharmacies. To enhance the value of PMHS for service users, providers should consider establishing other methods of access, such as email and video consultation. Considering the uncertainty around the future of PMHS, research should establish the best way to support all patients and carers regarding medicines following hospital discharge.

Sexual health services in community pharmacy for women on opioid substitution treatment: a qualitative study.

BACKGROUND: Women on opioid substitution treatment (WOST) are at heightened risk for the sexual transmission of sexually transmitted infections and blood-borne viruses. This study aimed to explore the opportunities to promote their sexual health in community pharmacies in UK. METHODS: Semi-structured interviews were conducted with 20 WOST and 14 community pharmacists (CPs). A focus group was run with three CPs. Participants were recruited in drug services and a service for sex workers (WOST), and in CP. Data collection took place between October 2016 and September 2017. Data were analyzed using Framework Analysis and directed Content Analysis. RESULTS: CPs could play a role in promoting sexual health among WOST. Sexual health screening, treatment and condom supply were suggested as potential ways of delivering pharmacy-based sexual health services. These services should be actively offered to WOST, delivered in a private space and free of cost. We identified several challenges to overcome in order to design and implement sexual health services for WOST in community pharmacies. CONCLUSIONS: This study highlights the potentially key role CPs can have promoting sexual health and addressing health inequities among WOST. Improvements in pharmacists' training are required in order to address stigma towards WOST, and promote trust and positive rapport. Structural changes are also needed to broaden the services available for this group of women and improve their access to healthcare.

Pharmacy professionals' experiences and perceptions of providing NHS patient medicines helpline services: a qualitative study.

BACKGROUND: Patient medicines helpline services (PMHS) have been established at some National Health Service (NHS) Trusts in England, with the aim of providing medicines-related support to patients after they have been discharged. Addressing an important knowledge gap, this qualitative study sought to examine pharmacy professionals' experiences and perceptions of their PMHS, including perceived benefits of the services, and areas for improvement. METHODS: Invitations to participate were sent to all NHS Trusts within England that were known to provide a PMHS (n = 117). Semi-structured interviews were conducted via telephone with 34 pharmacy professionals who provide a PMHS (female = 76%, male = 24%; predominantly from Acute NHS Trusts, 76%). Interviews were audio-recorded and transcribed verbatim. The RE-AIM framework for evaluating interventions (RE-AIM: Reach, Effectiveness, Adoption, Implementation, Maintenance) informed the development of the interview schedule and the analysis of the data using framework analysis. RESULTS: Two themes were generated from the analysis: Resources, and Perceived benefits. Findings illustrate how providing a PMHS with limited resources (e.g., no specific funding, understaffed) negatively impacts the implementation, maintenance and reach of PMHS, and the ability to evidence their effectiveness. Despite operating with limited resources, PMHS are considered to have many benefits for patients and healthcare organisations (e.g., providing a 'safety net' to patients during the transfer of care period, providing reassurance to patients, helping to optimise patients' medicines, resolving medicines-related errors, reducing the burden upon other services, and providing the potential to improve hospital services based upon the content of enquiries). However, actually establishing the effectiveness and cost-effectiveness of PMHS is challenging due to perceived logistical difficulties of collecting data, and the difficulty measuring hard outcomes (e.g., prevention of readmissions). CONCLUSIONS: PMHS are typically perceived to be under-resourced, although they are considered by pharmacy professionals to have several benefits for service users and NHS Trusts. For those sites that provide a PMHS, we recommend using enquiry data to improve hospital services, and to share ideas for implementing and maintaining a PMHS within a resource-limited context. High-quality research is needed to evidence the effectiveness and cost-effectiveness of PMHS, which may help to secure adequate resources for this service in the future.

Navigating environmental constraints to injection preparation: the use of saliva and other alternatives to sterile water among unstably housed PWID in London.

BACKGROUND: The United Kingdom is experiencing an increase in drug-related deaths and serious bacterial infections among its most vulnerable citizens. Cuts to essential services, coupled with a growing homeless population, create a challenging environment to tackle this public health crisis. In this paper, we highlight an underexplored environmental constraint faced by people living and injecting drugs on the streets. Access to water for injection is restricted in the UK, due to legislative and financial barriers. Austerity measures, such as public toilet closures, further restrict the ability of people made homeless to access clean water and protect themselves from health harms. METHODS: We generated questionnaire (n = 455) and in-depth qualitative interview (n = 32) data with people who inject drugs in London for the Care and Prevent study. Participants provided detail on their life history; drug use, injecting and living environments; health conditions and care seeking practices. FINDINGS: A high proportion of the survey sample reported lifetime history of street homelessness (78%), bacterial infections (65%) and related hospitalisation (30%). Qualitative accounts highlight unsafe, potentially dangerous, injection practices in semi-public spaces. Multiple constraints to sourcing sterile water for injection preparation were reported. Alternatives to sterile water included puddle water, toilet cistern water, whisky, cola soda and saliva. Participants who injected heroin and crack cocaine together unanimously reported adding water at two stages during injection preparation: first, adding water as a vehicle for heroin (which was then heated); second, adding cold water to the heroin mixture prior to adding the crack cocaine. This new finding of a stage addition of solvent may represent an additional risk of infection. CONCLUSION: Currently, harm reduction equipment and resources for safe injecting are not meeting the needs of people who inject drugs who are street homeless or unstably housed. Preparation of injections with non-sterile water sources could precipitate bacterial and fungal infections, particularly when used without the application of heat. It is crucial that water for injection, also skin cleaning, is made available for the unstably housed and that harm reduction messaging is tailored to speak to the everyday realities of people who prepare and inject drugs in public spaces.

Correction to: Navigating environmental constraints to injection preparation: the use of saliva and other alternatives to sterile water among unstably housed PWID in London.

An amendment to this paper has been published and can be accessed via the original article.

Qualitative exploration of the experiences of men who use drugs of obtaining psychoactive medicinal products in Jordan.

In Jordan, almost any medication can be bought from pharmacies. This ready availability is linked with abuse. Previous literature describes medicine abuse from pharmacists' and general public perspectives. Here we investigate experiences of 17 men in addiction treatment in Amman (21-39 years) of obtaining psychoactive medicines. Alprazolam, clonazepam, bromazepam and tramadol were most commonly abused. Psychoactive medicines were obtained from street dealers, but pharmacies were preferred. Regulations appears ineffective; lack of understanding of pharmacists of the abuse potential of some medicines was perceived; 'softening rules' on supply was attributed to cultural and social norms around familiarity.

Synthetic Cannabinoid Receptor Agonists Detection Using Fluorescence Spectral Fingerprinting.

Synthetic cannabinoid receptor agonists (SCRAs), termed "Spice" or "K2", are molecules that emulate the effects of the active ingredient of marijuana, and they have gained enormous popularity over the past decade. SCRAs are Schedule 1 drugs that are highly prevalent in the U.K. prison system and among homeless populations. SCRAs are highly potent and addictive. With no way to determine the dose/amount at the point-of care, they pose severe health risks to users, including psychosis, stroke, epileptic seizures, and they can kill. SCRAs are chemically diverse, with over a hundred compounds used as recreational drugs. The chemical diversity of SCRA structures presents a challenge in developing detection modalities. Typically, GC-MS is used for chemical identification; however, this cannot be in place in most settings where detection is critical, e.g., in hospital Emergency Departments, in custody suites/prisons, or among homeless communities. Ideally, real time, point-of-care identification of SCRAs is desirable to direct the care pathway of overdoses and provide information for informed consent. Herein, we show that fluorescence spectral fingerprinting can be used to identify the likely presence of SCRAs, as well as provide more specific information on structural class and concentration (∼1 µg mL-1). We demonstrate that that fluorescence spectral fingerprints, combined with numerical modeling, can detect both parent and combusted material, and such fingerprinting is also practical for detecting them in oral fluids. Our proof-of-concept study suggests that, with development, the approach could be useful in a range of capacities, notably in harm reduction for users of Spice/K2.

Injecting-related health harms and overuse of acidifiers among people who inject heroin and crack cocaine in London: a mixed-methods study.

BACKGROUND: Venous access is a priority for people who inject drugs (PWID). Damage and scarring of peripheral veins can exacerbate health harms, such as skin and soft tissue infections (SSTI), and promote transitions to femoral and subcutaneous injecting. Brown heroin available in Europe requires acidification for injection preparation. In this paper, we present mixed-methods data to explore our hypothesis of a link between overly acidic injection solutions, venous damage and SSTI risk. METHODS: We present a structured survey (n = 455) and in-depth qualitative interview (n = 31) data generated with PWID in London for the Care & Prevent study. Participants provided life history data and detail on injecting environments and drug preparation practices, including the use of acidifiers. Bivariate and multivariate analyses were conducted using a logistic regression for binary outcomes to explore associations between outcomes and excessive acidifier use. Grounded theory principles informed inductive qualitative analysis. Mixed-methods triangulation was iterative with results comparison informing the direction and questions asked of further analyses. RESULTS: Of the 455 participants, most (92%) injected heroin and/or crack cocaine, with 84% using citric as their primary acid for drug preparation. Overuse of acidifier was common: of the 418 who provided an estimate, 36% (n = 150) used more than ½ a sachet, with 30% (n = 127) using a whole sachet or more. We found associations between acidifier overuse, femoral injecting and DVT, but not SSTI. Qualitative accounts highlight the role of poor heroin quality, crack cocaine use, information and manufacturing constraints in acidifier overuse. Painful injections and damage to peripheral veins were common and often attributed to the use of citric acid. CONCLUSIONS: To reduce injecting-related injury and associated consequences, it is crucial to understand the interplay of environmental and practice-based risks underpinning venous damage among PWID. Overuse of acidifier is a modifiable risk factor. In the absence of structural supports such as safe injecting facilities or the prescribing of pharmaceutical diamorphine, there is an urgent need to revisit injecting paraphernalia design and distribution in order to alleviate health harms and distress among the most marginalised.

Operating a patient medicines helpline: a survey study exploring current practice in England using the RE-AIM evaluation framework.

BACKGROUND: Patient medicines helplines provide a means of accessing medicines-related support following hospital discharge. However, it is unknown how many National Health Service (NHS) Trusts currently provide a helpline, nor how they are operated. Using the RE-AIM evaluation framework (Reach, Effectiveness, Adoption, Implementation, and Maintenance), we sought to obtain key data concerning the provision and use of patient medicines helplines in NHS Trusts in England. This included the extent to which the delivery of helplines meet with national standards that are endorsed by the Royal Pharmaceutical Society (standards pertaining to helpline access, availability, and promotion). METHODS: An online survey was sent to Medicines Information Pharmacists and Chief Pharmacists at all 226 acute, mental health, specialist, and community NHS Trusts in England in 2017. RESULTS: Adoption: Fifty-two percent of Trusts reported providing a patient medicines helpline (acute: 67%; specialist: 41%; mental health: 29%; community: 18%). Reach: Helplines were predominantly available for discharged inpatients, outpatients, and carers (98%, 95% and 93% of Trusts, respectively), and to a lesser extent, the local public (22% of Trusts). The median number of enquiries received per week was five. IMPLEMENTATION: For helpline access, 54% of Trusts reported complying with all 'satisfactory' standards, and 26% reported complying with all 'commendable' standards. For helpline availability, the percentages were 86% and 5%, respectively. For helpline promotion, these percentages were 3% and 40%. One Trust reported complying with all standards. Maintenance: The median number of years that helplines had been operating was six. Effectiveness: main perceived benefits included patients avoiding harm, and improving patients' medication adherence. CONCLUSIONS: Patient medicines helplines are provided by just over half of NHS Trusts in England. However, the proportion of mental health and community Trusts that operate a helpline is less than half of that of the acute Trusts, and there are regional variations in helpline provision. Adherence to the national standards could generally be improved, although the lowest adherence was regarding helpline promotion. Recommendations to increase the use of helplines include increasing the number of promotional methods used, the number of ways to contact the service, and the number of hours that the service is available.

Development of a filter to prevent infections with spore-forming bacteria in injecting drug users.

BACKGROUND: In heroin injectors, there have been a number of outbreaks caused by spore-forming bacteria, causing serious infections such as anthrax or botulism. These are, most likely, caused by injecting contaminated heroin, and our aim was to develop a filter that efficiently removes these bacteria and is also likely to be acceptable for use by people who inject drugs (i.e. quick, simple and not spoil the hit). METHODS: A prototype filter was designed and different filter membranes were tested to assess the volume of liquid retained, filtration time and efficiency of the filter at removing bacterial spores. Binding of active ingredients of heroin to different types of membrane filters was determined using a highly sensitive analytical chemistry technique. RESULTS: Heroin samples that were tested contained up to 580 bacteria per gramme, with the majority being Bacillus spp., which are spore-forming soil bacteria. To remove these bacteria, a prototype filter was designed to fit insulin-type syringes, which are commonly used by people who inject drugs (PWIDs). Efficient filtration of heroin samples was achieved by combining a prefilter to remove particles and a 0.22 µm filter to remove bacterial spores. The most suitable membrane was polyethersulfone (PES). This membrane had the shortest filtration time while efficiently removing bacterial spores. No or negligible amounts of active ingredients in heroin were retained by the PES membrane. CONCLUSIONS: This study successfully produced a prototype filter designed to filter bacterial spores from heroin samples. Scaled up production could produce an effective harm reduction tool, especially during outbreaks such as occurred in Europe in 2009/10 and 2012.

Class I histone deacetylase inhibition modulates metalloproteinase expression and blocks cytokine-induced cartilage degradation.

OBJECTIVE: To examine the ability of a broad-spectrum histone deacetylase (HDAC) inhibitor to protect cartilage in vivo, and to explore the effects of class-selective HDAC inhibitors and small interfering RNA (siRNA)-induced knockdown of HDACs on metalloproteinase expression and cartilage degradation in vitro. METHODS: A destabilization of the medial meniscus (DMM) model was used to assess the in vivo activity of the HDAC inhibitor trichostatin A (TSA). Human articular chondrocytes (HACs) and SW-1353 chondrosarcoma cells were treated with cytokines and TSA, valproic acid, MS-275, or siRNA, and quantitative reverse transcription-polymerase chain reaction was performed to determine the effect of treatment on metalloproteinase expression. HDAC inhibitor activity was detected by Western blotting. A bovine nasal cartilage (BNC) explant assay was performed to measure cartilage resorption in vitro. RESULTS: Systemically administered TSA protected cartilage in the DMM model. TSA, valproic acid, and MS-275 repressed cytokine-induced MMP1 and MMP13 expression in HACs. Knockdown of each class I HDAC diminished interleukin-1-induced MMP13 expression. All of the HDAC inhibitors prevented degradation of BNC, in which TSA and MS-275 repressed cytokine-induced MMP expression. CONCLUSION: Inhibition of class I HDACs (HDAC-1, HDAC-2, HDAC-3) by MS-275 or by specific depletion of HDACs is capable of repressing cytokine-induced metalloproteinase expression in cartilage cells and BNC explants, resulting in inhibition of cartilage resorption. These observations indicate that specific inhibition of class I HDACs is a possible therapeutic strategy in the arthritides.

Associations between socioeconomic, parental and home environment factors and fruit and vegetable consumption of children in grades five and six in British Columbia, Canada.

BACKGROUND: Regular fruit and vegetable (FV) consumption has been associated with reduced chronic disease risk. Evidence from adults shows a social gradient in FV consumption. Evidence from pre-adolescent children varies and there is little Canadian data. This study assessed the FV intake of school children in British Columbia (BC), Canada to determine whether socio-economic status (SES), parental and the home environment factors were related to FV consumption. METHODS: As part of the BC School Fruit and Vegetable Nutrition Program, 773 British Columbia fifth-and sixth-grade school children (Mean age 11.3 years; range 10.3-12.5) and their parents were surveyed to determine FV consumption and overall dietary intake. Students completed a web-based 24-hour dietary food recall, and a student measure of socio-economic status (The Family Affluence Scale). Parents completed a self-administered survey about their education, income, home environment and perceptions of their neighbourhood and children's eating habits. Correlations and multiple regression analyses were used to examine the association between SES, parental and home environment factors and FV consumption. RESULTS: Approximately 85.8% of children in this study failed to meet minimum Canadian guidelines for FV intake (6 servings). Parent income and education were not significantly associated with child FV consumption but were associated with each other, child-reported family affluence, neighbourhood environment, access to FV, and eating at the table or in front of the television. Significant positive associations were found between FV consumption and child-reported family affluence, meal-time habits, neighbourhood environment and parent perceptions of the healthiness of their child's diet; however, these correlations were weak (ranging from .089-.115). Multiple regression analysis showed that only child-reported family affluence significantly predicted FV consumption (std-ß = 0.096 95% CI = 0.01 to 0.27). CONCLUSIONS: The majority of children in our study were not meeting guidelines for FV intake irrespective of SES, parent perceptions or home environment, making this a population wide concern. An almost trivial socio-economic gradient was observed for the child-reported SES measure only. These results are consistent with several other studies of children. Longitudinal research is needed to further explore individual and social factors associated with FV consumption in childhood and their development over time.

Doping in gymnasiums in Amman: the other side of prescription and nonprescription drug abuse.

This study investigated the abuse of over-the-counter (OTC) products (e.g., proteins, dietary supplements) and prescription drugs (e.g., hormones) in gymnasiums in Amman by random distribution of a structured questionnaire to 375 gym clients (November 2012-February 2013). Data were analyzed using SPSS for Windows (version 17.0). A total of 31 (8.8%) clients admitted to using 21 products (mentioned 71 times) of anabolic steroids and other hormones (e.g., growth hormone and thyroxine) to increase muscular power at the gym or build muscle mass. Abuse of different prescription and OTC drugs among gymnasium clients is present in Jordan, but current methods for controlling the problem are ineffective. Better methods should be developed. The study's limitations are noted.

Facilitators and barriers to community pharmacy PrEP delivery: a scoping review.

INTRODUCTION: Pre-exposure prophylaxis (PrEP) is an effective medication to reduce the risk of acquiring HIV. PrEP is available free of charge in the UK from sexual health clinics. Expanding PrEP delivery to community pharmacies holds promise and aligns with UK government goals to eliminate new cases of HIV by 2030. The aim of this scoping review was to describe the existing evidence about the barriers to and facilitators of community pharmacy oral PrEP delivery, for pharmacists and pharmacy clients, as aligned with the Capacity Opportunity, Motivation Behaviour (COM-B) Model. METHODS: Five bibliographic and five review databases were searched from inception to August 2023. Literature of any study design was included if it discussed barriers and facilitators of community pharmacy PrEP delivery. Trial registrations, protocols and news articles were excluded. RESULTS: A total of 649 records were identified, 73 full texts were reviewed and 56 met the inclusion criteria, predominantly from high-income/westernized settings. Most of the included literature was original research (55%), from the United States (77%) conducted during or after the year 2020 (63%). Barriers to PrEP delivery for pharmacists included lack of knowledge, training and skills (capability), not having the necessary facilities (opportunity), concern about the costs of PrEP and believing that PrEP use could lead to risk behaviours and sexually transmitted infections (motivation). Facilitators included staff training (capability), time, the right facilities (opportunity), believing PrEP could be a source of profit and could reduce new HIV acquisitions (motivation). For clients, barriers included a lack of PrEP awareness (capability), pharmacy facilities (opportunity) and not considering pharmacists as healthcare providers (motivation). Facilitators included awareness of PrEP and pharmacist's training to deliver it (capability), the accessibility of pharmacies (opportunity) and having an interest in PrEP (motivation). DISCUSSION: To effectively enhance oral PrEP delivery in UK community pharmacies, the identified barriers and facilitators should be explored for UK relevance, addressed and leveraged at the pharmacy team, client and care pathway level. CONCLUSIONS: By comprehensively considering all aspects of the COM-B framework, community pharmacies could become crucial providers in expanding PrEP accessibility, contributing significantly to HIV prevention efforts.

cAMP response element-binding (CREB) recruitment following a specific CpG demethylation leads to the elevated expression of the matrix metalloproteinase 13 in human articular chondrocytes and osteoarthritis.

Osteoarthritis is a degenerative joint disease characterized by a progressive and irreversible loss of the articular cartilage, due in main part to the cleavage of type II collagen within the matrix by the enzyme matrix metalloproteinase (MMP)13. Here, we examined the methylation status of MMP13 promoter and report the demethylation of specific CpG dinucleotides within its promoter in osteoarthritic compared to normal cartilage, which correlates with increased MMP13 expression. Of the promoter CpG sites examined, the -104 CpG was consistently demethylated following treatment of human articular chondrocytes with 10 µM DNA-methyltransferase inhibitor 5-aza-2'-deoxycytidine, again correlating with increased MMP13 expression. Methylation of the -104 CpG site resulted in reduced promoter activity in the chondrosarcoma cell line SW1353 as shown by CpG-free luciferase reporter. Using electrophoretic mobility shift assays, we identified CREB as the regulating factor able to only bind to the MMP13 promoter when the -104 CpG is demethylated, and confirmed this binding by chromatin immunoprecipitation. Finally, we demonstrated that CREB induces MMP13 expression only following treatment of SW1353 with 0.5 µM Ca(2+) ionophore A23187. In summary, the -104 CpG is demethylated in osteoarthritic cartilage, correlating with the elevated MMP13 expression and cartilage destruction, providing a highly novel link between epigenetic status and arthritic disease.