A brief review of current treatment options for osteoarthritis including disease-modifying osteoarthritis drugs (DMOADs) and novel therapeutics.

Osteoarthritis (OA) is a chronic disorder caused by degenerative changes in articular cartilage, which are mainly manifests as degeneration of cartilage, subchondral bone remodeling, as well as synovial inflammation. Over the next few decades, OA and its burden will continue to increase worldwide, posing a major public health challenge for the foreseeable future. Treatment for OA includes non-pharmacological, pharmacological, and surgical treatments. Existing conservative treatments and joint surgery can only alleviate the symptoms and cannot be cured, so new therapies for OA are urgently needed. Since advances in the understanding of OA pathophysiology, researchers have identified some potential therapeutic targets against degeneration of cartilage, subchondral bone remodeling and synovial inflammation, enabling development of the disease-modifying OA drugs (DMOADs). Additionally, a number of new technologies are also being investigated for treating OA, such as RNA interference (RNAi), CRISPR/Cas9 and PROTAC. The goal of this review is to describe the current development status of DMOADs and to discuss the potential of emerging therapeutic approaches for treating OA, thus providing a reference for OA treatments.

Grisel's Syndrome After COVID-19 in a Pediatric Patient: A Case Report.

An eight-year-old female presenting with posterior neck pain and torticollis who had been diagnosed with coronavirus disease 2019 (COVID-19) three weeks earlier was radiographed and diagnosed with atlantoaxial rotatory fixation (AARF). Following treatment with non-steroidal anti-inflammatory drugs (NSAIDs), the posterior neck pain improved, and the torticollis was cured. Symptoms returned after two weeks, and computed tomography showed a 3.94 mm atlantodental interval and axis rotation. The patient was diagnosed with AARF relapse; symptoms resolved spontaneously prior to subsequent examination, and no further relapses were observed. This case highlights the need for clinicians to be aware that AARF may develop after COVID-19. Treatment options should be carefully considered.

Design, synthesis and biological evaluation of sulfamethazine derivatives as potent neuraminidase inhibitors.

Aim: The purpose of this study is to design and synthesize a new series of sulfamethazine derivatives as potent neuraminidase inhibitors. Materials & methods: A sulfamethazine lead compound, ZINC670537, was first identified by structure-based virtual screening technique, then some novel inhibitors X1-X10 based on ZINC670537 were designed and synthesized. Results: Compound X3 exerts the most good potency in inhibiting the wild-type H5N1 NA (IC50 = 6.74 µM) and the H274Y mutant NA (IC50 = 21.09 µM). 150-cavity occupation is very important in determining activities of these inhibitors. The sulfamethazine moiety also plays an important role. Conclusion: Compound X3 maybe regard as a good anti-influenza candidate to preform further study.

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Aneuploidy underlies brefeldin A-induced antifungal drug resistance in Cryptococcus neoformans.

Cryptococcus neoformans is at the top of the list of "most wanted" human pathogens. Only three classes of antifungal drugs are available for the treatment of cryptococcosis. Studies on antifungal resistance mechanisms are limited to the investigation of how a particular antifungal drug induces resistance to a particular drug, and the impact of stresses other than antifungals on the development of antifungal resistance and even cross-resistance is largely unexplored. The endoplasmic reticulum (ER) is a ubiquitous subcellular organelle of eukaryotic cells. Brefeldin A (BFA) is a widely used chemical inducer of ER stress. Here, we found that both weak and strong selection by BFA caused aneuploidy formation in C. neoformans, mainly disomy of chromosome 1, chromosome 3, and chromosome 7. Disomy of chromosome 1 conferred cross-resistance to two classes of antifungal drugs: fluconazole and 5-flucytosine, as well as hypersensitivity to amphotericin B. However, drug resistance was unstable, due to the intrinsic instability of aneuploidy. We found overexpression of AFR1 on Chr1 and GEA2 on Chr3 phenocopied BFA resistance conferred by chromosome disomy. Overexpression of AFR1 also caused resistance to fluconazole and hypersensitivity to amphotericin B. Furthermore, a strain with a deletion of AFR1 failed to form chromosome 1 disomy upon BFA treatment. Transcriptome analysis indicated that chromosome 1 disomy simultaneously upregulated AFR1, ERG11, and other efflux and ERG genes. Thus, we posit that BFA has the potential to drive the rapid development of drug resistance and even cross-resistance in C. neoformans, with genome plasticity as the accomplice.

Consumer awareness and knowledge regarding use of non-steroidal anti-inflammatory drugs (NSAIDs) in a metropolitan area.

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) have well-known adverse effects, and numerous studies have shown inappropriate behaviors regarding their use. The primary aim of this study was to analyze the knowledge, attitudes, and behaviors regarding the use of NSAIDs simultaneously in one of the largest and most populated areas of Italy, Naples. Methods: From 2021 December 14th to 2022 January 4th, a cross-sectional survey study was conducted among community centers, working places, and universities using a snowball sampling method. For inclusion in the study, the participants were required to be at least 18 years old and residents in the metropolitan area of Naples. Three multiple linear regression analysis (MLRA) models were developed by including variables that could potentially be associated with the following outcomes of interest: knowledge (Model I), attitudes (Model II), and behavior (Model III) regarding the use of NSAIDs. Results: Data were acquired from 1,012 questionnaires administered to subjects evenly divided by gender with an average age of 36.8 years and revealed that only 7.9% of the participants self-admittedly did not take NSAIDs, while approximately half the participants (50%) admitted to occasionally using them. The results showed a statistically significant correlation between attitudes regarding the appropriate use of NSAIDs and less knowledge. The regression analyses indicated that behaviors regarding the appropriate use of NSAIDs were statistically significant in younger respondents, non-smokers, and those without children. These interesting results showed that behaviors regarding the appropriate use of NSAIDs were significantly higher among respondents with less knowledge and more positive attitudes. Conclusion: According to the collected data and statistical analysis results, it is possible to identify factors that can greatly affect inappropriate behaviors regarding the use of NSAIDs and establish targeted prevention programs.

Effect of Terpenes on the Enhancement of Skin Permeation of Lipophilic Drugs: A Systematic Review.

Objectives: The stratum corneum (SC) remains an obstacle to the passage of drugs applied topically. Several investigations have focused on enhancing the penetration of drugs through the SC by integrating permeation enhancers (PE) into the drug formulation. Terpenes are among the PE utilized in formulations and are categorized by the regulatory bodies as generally recognized as safe (GRAS). This study aimed to comparatively analyze the skin permeation enhancing effect of terpenes on lipophilic drugs. Methods: The present study reviewed the effects of terpenes on the permeation of lipophilic small-molecule drugs through the skin using original research published between 2000 - 2022 retrieved from PubMed®. The search phrase used was (lipophilic drug) AND (terpene) AND (permeation enhancer). Results: Terpenes increase the percutaneous permeation of lipophilic small molecule drugs by 1.06 - 256.80-fold. Linear correlation analysis of terpenes' cLog P with enhancement ratio (ER) revealed moderate and strong positive correlations in pig skin (r = 0.21) and mouse skin (r = 0.27), and rat skin (r = 0.41) and human skin (r = 0.67), respectively. Drug cLog P is a poor (r = -0.06) predictor of permeation enhancement. Terpenes with cLog P higher than 2.40 had ER greater than 10. Higher ERs (>30) were recorded for nerolidol, carvacrol, borneol, terpineol, limonene, menthone, pulegone, and menthol among the terpene-chemical penetration enhancers. Conclusion: cLog P of terpene-based chemical permeation enhancers (CPE) is strongly correlated with ER of lipophilic drugs across human skin. Non-polar groups in terpenes and hydrogen bond interactions by terpenes with SC lipid enhance cutaneous drug penetration of lipophilic drugs.

A Feasibility Study on Re-establishing the Bioavailability/Bioequivalence Unit of the Department of Pharmacology and Toxicology, College of Medicine-University of the Philippines Manila.

Objectives: The Bioavailability/Bioequivalence Unit (BA/BE Unit) of the Department of Pharmacology and Toxicology, College of Medicine, University of the Philippines Manila which has not been operational since 2012, is due for renewal of its accreditation. To date, there are only three Philippine Food and Drug Administration-accredited laboratories that perform bioequivalence studies in the Philippines. One of the prerequisites of registering specific generic medicines is the conduct of Bioequivalence (BE) studies which are performed to ensure that the generic drug is at par with the innovator drug. Thus, this study aimed to determine the feasibility of re-establishing the BA/BE Unit as a bioequivalence testing center. Methods: The feasibility study done is a qualitative descriptive analysis based on expansive literature review and performance of SWOT analysis within the BA/BE unit. Literatures were selected based on its assessed relevance to the study. The databases checked were PubMed and Google Scholar. The terms used were from the Medical Subject Heading (MeSH) including feasibility studies, therapeutic equivalency, and generic drugs. Literature review was performed on the factors affecting the four types of feasibility studies (market, technical, financial, and organizational). A SWOT analysis of the BA/BE Unit was done through the review of records and documents of previous BE studies and focus group discussion among the BA/BE Unit team members. Results: The BA/BE Unit conducted 24 bioequivalence studies from 2006-2009 and still receives inquiries from drug companies. It implements its QMS throughout the pre-analytical, analytical, and post-analytical stages of the workflow. Its organizational structure consists of qualified professionals with updated GCP and GLP certificates. Because of the adequately equipped facility, lower honoraria for government-employed personnel, and lower expenses for laboratories and in-patient admissions, the cost of conducting a bioequivalence study in the BA/BE Unit will be lower than in other BE centers. Conclusion: Based on the SWOT analysis and market, technical, financial, and organizational considerations, re-establishing the BA/BE Unit as a bioequivalence testing center is feasible.

A comprehensive review of the application of Zr-based metal-organic frameworks for electrochemical sensors and biosensors.

A family of inorganic-organic hybrid crystalline materials made up of organic ligands and metal cations or clusters is known as metal-organic frameworks (MOFs). Because of their unique stability, intriguing characteristics, and structural diversity, zirconium-based MOFs (Zr-MOFs) are regarded as one of the most interesting families of MOF materials for real-world applications. Zr-MOFs that have the ligands, metal nodes, and guest molecules enclosed show distinct electrochemical reactions. They can successfully and sensitively identify a wide range of substances, which is important for both environmental preservation and human health. The rational design and synthesis of Zr-MOF electrochemical sensors and biosensors, as well as their applications in the detection of drugs, biomarkers, pesticides, food additives, hydrogen peroxide, and other materials, are the main topics of this comprehensive review. We also touch on the current issues and potential future paths for Zr-MOF electrochemical sensor research.

Predictors of changes in marijuana consumption in Germany during the covid-19 pandemic.

During the Covid-19 pandemic Germany experienced its first increase in the proportion of heavy cannabis users since 1995. With the expected nationwide decriminalization of cannabis before 2025, we investigate the potential causes for that increase. Data were from the 2021 European Web Survey on Drugs (EWSD) including 762 12-month marijuana users from Germany (72.9% male, mean age = 29.5 years). Both heavy and regular cannabis consumers reported an increase in marijuana consumption during the pandemic, with infrequent users reporting a decrease. Using multinomial logistic regression, we found younger individuals (OR = 0.95 [95% CI = 0.92, 0.98]) and those not pursuing or completing higher education (OR = 1.86 [1.23, 2.81]) had increased use. Additionally, using cannabis to self-medicate (OR = 2.79 [1.56, 4.99]) and purchasing marijuana (OR = 2.26 [1.35, 3.77]) was associated with increased use. We found, relative to infrequent users, both regular (OR = 4.00 [2.39, 6.72]) and notably heavy users (OR = 31.17 [12.10, 80.32]) were more likely to use cannabis to self-medicate. Both regular (OR = 4.09 [2.47, 6.77]) and especially heavy users (OR = 13.53 [6.74, 27.16]) were also more likely to purchase marijuana. Heavy users were also more likely to be past 30-day tobacco users (OR = 5.92 [2.81, 12.45]). We identified the self-reported motivation of using cannabis to self-medicate as well as act of purchasing marijuana as having the strongest relation to being a heavy user and increasing marijuana use during the Covid-19 pandemic.

Nanomedicine And Nanotheranostics: Special Focus on Imaging of Anticancer Drugs Induced Cardiac Toxicity.

Cardiotoxicity, the often-overlooked second leading cause of death in cancer patients, has been associated with certain anticancer drugs. These drugs can induce cardiac damage through various pathways, and their adverse effects on the heart are not fully understood. Cardiotoxicity is a major issue in cancer treatment, particularly with chemotherapeutics, because it can cause cardiac dysfunction such as hypotension, heart failure, and even death. Doxorubicin, 5-fluorouracil, and trastuzumab, all of which are very potent anticancer drugs, are known to cause cardiotoxicity. When it comes to lowering cardiotoxicity and alleviating the harmful effects of chemotherapy medications, nanomedicine has the potential to transport therapeutic molecules. Nanotheranostics offers novel options for identifying and treating cardiotoxicity resulting from a wide range of substances, including anticancer medications. Additionally, theranostics platforms such as micellar systems, carbon-based nanomedicine, solid lipid nanoparticles, polymeric nanoparticles, and liposomes can transport chemotherapeutic medications while minimising their cardiotoxicity. The present level of understanding of the molecular and cellular processes that lead to cardiotoxicity in reaction to both traditional chemotherapy and targeted drug delivery systems is summarised in this article. This review delves into nanomedicine and nanotheranostics, with an emphasis on reducing anticancer medication-induced cardiac toxicity. Nanotheranostics provide potential solutions for early diagnosis and tailored therapy of heart injury by combining diagnostic and therapeutic capabilities into nanomedicine.

Deprescribing antihypertensive drugs in frail older adults.

Antihypertensive drugs are commonly used by older adults because of the high prevalence of cardiovascular disease and its risk factors, and the increased absolute benefit of blood pressure reduction with increasing age. Clinical trials of blood pressure reduction in older adults have generally excluded older adults with multimorbidity, frailty and limited life expectancy. In this population, the benefit-harm ratio of aggressive blood pressure lowering may become unfavourable; a more relaxed blood pressure target may be appropriate; and deprescribing (cessation or dose reduction) of one or more antihypertensive drugs can be considered. Before deprescribing an antihypertensive drug, it is important to consider other indications for which it may have been prescribed (e.g. heart failure with reduced ejection fraction, diabetic nephropathy, atrial fibrillation). Evidence from randomised controlled deprescribing trials indicates that it is possible to deprescribe antihypertensives in frail older people. However, some patients may experience an increase in blood pressure that warrants restarting the drug. There are limited data on long-term outcomes (follow-up in deprescribing trials ranged from 4 to 56 weeks). The risk of adverse outcomes associated with deprescribing, such as withdrawal effects, can be minimised through appropriate planning, patient engagement, dose tapering and monitoring.

One Year of Long-Acting Cabotegravir and Rilpivirine in People With Human Immunodeficiency Virus and Long Exposure to Antiretroviral Therapy: Data From the SCohoLART Study.

Background: The aim of the study was to evaluate the 12-month cumulative probability of treatment discontinuation (TD) in people with human immunodeficiency virus (HIV; PWH) and a long exposure to antiretroviral therapy (ART) switching to long-acting cabotegravir and rilpivirine (CAB/RPV). Methods: SCohoLART is a single-center, prospective, cohort study designed to collect both samples and clinical data from PWH with virological suppression who switched to bimonthly long-acting CAB/RPV. TD occurred at switch to another regimen for any reason including virological failure (VF); VF was defined as HIV RNA levels ≥50 copies/mL at 2 consecutive measurements or a single HIV RNA level ≥1000 copies/mL. Results were reported as median (interquartile range [IQR]) or frequency (percentage). Cumulative probabilities of TD were estimated using Kaplan-Meier curves. Results: We evaluated 514 participants; 467 (90.9%) were male, and their median age (IQR) was 49 (40-56) years. At the time of switching, the median time from HIV diagnosis and the median duration of ART were 14.0 (IQR, 8.8-20.5) and 11.4 (7.9-17.4) years, respectively; before starting CAB/RPV, the median number of antiretroviral regimens was 3 (2-4). During a median study follow-up (IQR) of 13.1 (9.1-15.5) months, 52 PWH (10.1%) experienced TD, including 4 (0.8%) for VF. The 12-month cumulative probability of TD was 11% (95% confidence interval, 8%-14%). The main cause of TD was injection site reaction (15 participants [28.8%]). Conclusions: The 1-year cumulative probability of TD with long-acting CAB/RPV was quite low in this cohort of people with a median exposure to ART of 10 years, in whom injection site reaction was the leading cause of TD. VFs were rare during study follow-up.

Profiling and assessing the risks of image- and performance-enhancing drugs use during the COVID-19 lockdown.

Background: Image and Performance-Enhancing Drugs (IPEDs) can enhance mental and physical capabilities and impact one's overall health. Initially confined in sport environments, IPEDs use has become increasingly widespread in a high-performing society. The present study was aimed at profiling IPEDs use during the COVID-19 lockdown among an international sample of young adults. Methods: A cross-sectional observational study was carried out in eight countries (United Kingdom, Italy, Lithuania, Hungary, Portugal, Spain, Brazil, and Japan) between April and May 2020. The survey questionnaire included validated measurements such as Exercise Addiction Inventory (EAI), Appearance Anxiety Inventory (AAI), and Self-Compassion Scale (SCS) as well as questions about the type of IPEDs, purchasing methods and socio-demographic information. Results: A total of 736 IPEDs users were included in the survey. Their mean age was 33.05 years (±SD = 10.06), and 64.2% were female participants. Overall, 6.8% were found at risk of exercise addiction (EAI >24), 27.6% presented high levels of appearance anxiety, and 24.9% revealed low levels of emotional regulation's self-compassion. Most participants (55.6%) purchased IPEDs through pharmacies/specialized shops, while 41.3% purchased IPEDs on the Internet. Online IPEDs buyers were mainly men who had higher scores on the Exercise Addiction Inventory. One or more IPEDs classifiable as "potentially risky" were used by 66.3% of the sample. Users of "potentially risky IPEDs" were younger and primarily men. They showed higher scores both on the Exercise Addiction Inventory and Appearance Anxiety Inventory. Conclusion: This study profiled users of IPEDs when the most restrictive COVID-19 lockdown policies were implemented in all the participating countries. More targeted post-COVID 19 prevention strategies should be implemented according to the emerged socio-demographic and psychopathological traits and cross-cultural differences emerged. Longitudinal studies will also be needed to determine the long-term effect of the COVID-19 lockdown on IPEDs consumption.

Hydrophobic deep eutectic solvent (HDES) as oil phase in lipid-based drug formulations.

There is increasing pharmaceutical interest in deep eutectic solvents not only as a green alternative to organic solvents in drug manufacturing, but also as liquid formulation for drug delivery. The present work introduces a hydrophobic deep eutectic solvent (HDES) to the field of lipid-based formulations (LBF). Phase behavior of a mixture with 2:1 M ratio of decanoic- to dodecanoic acid was studied experimentally and described by thermodynamic modelling. Venetoclax was selected as a hydrophobic model drug and studied by atomistic molecular dynamics simulations of the mixtures. As a result, valuable molecular insights were gained into the interaction networks between the different components. Moreover, experimentally the HDES showed greatly enhanced drug solubilization compared to conventional glyceride-based vehicles, but aqueous dispersion behavior was limited. Hence surfactants were studied for their ability to improve aqueous dispersion and addition of Tween 80 resulted in lowest droplet sizes and high in vitro drug release. In conclusion, the combination of HDES with surfactant(s) provides a novel LBF with high pharmaceutical potential. However, the components must be finely balanced to keep the integrity of the solubilizing HDES, while enabling sufficient dispersion and drug release.

Acute liver failure with a massive upper GI bleed meeting the criteria of MIS-C.

Multisystem inflammatory syndrome in children (MIS-C) is a known complication of COVID-19. There is still limited knowledge about this condition. Here, we report the case of a previously healthy toddler boy, who presented with acute liver failure and duodenal lesions resulting in severe haematemesis and haemorrhagic shock, requiring intensive care unit care. The patient had persistent transaminitis, a deranged coagulation profile, inflammatory markers were elevated, and laboratory tests were negative for common infectious hepatitis aetiologies as well as COVID-19 Reverse transcription polymerase chain reaction. His COVID-19 antibody was reactive. Upper gastrointestinal endoscopy revealed a Forrest grade III duodenal ulcer. Looking into the constellation of symptoms and laboratory findings a confirmed diagnosis of acute viral hepatitis caused by MIS-C was made. Hence, he was given intravenous methylprednisolone along with intravenous immunoglobulins, after which he improved clinically and transaminitis resolved. The patient was discharged on clinical improvement and was doing fine on follow-up up to 6 months.

Comparison of disease-modifying anti-rheumatic drugs and hyperbaric oxygen therapy in the experimental model of rheumatoid arthritis in rats.

In this study, we wanted to investigate the effectiveness of combining disease-modifying anti-rheumatic drugs (DMARD) with hyperbaric oxygen therapy (HBOT) in reducing inflammation in a rheumatoid arthritis (RA) model using rats. We divided 56 male Sprague-Dawley rats into seven groups and induced RA using complete Freund's adjuvant. Some groups received HBOT, whereas others were given etanercept or leflunomide. We started the treatment on the 10th day after inducing RA and continued it for 18 days. To evaluate the effectiveness of the treatments, we measured paw swelling and used X-rays to examine the joints before and after the treatment. We also analysed the levels of two inflammatory markers, tumour necrosis factor (TNF)-α and interleukin (IL)-1ß, using an enzyme-linked immunosorbent assay. Additionally, we conducted histological analysis and assessed the expressions of anti-IL-1ß and anti-TNF-α antibodies. All the treatment groups showed a significant decrease in arthritis scores, paw swelling and levels of TNF-α and IL-1ß. The X-ray images revealed improvements in joint structure, and the histopathological analysis showed reduced inflammation and collagen abnormalities. Combining DMARD with HBOT had similar effects to individual therapies, suggesting a cost-effective and potentially safer approach for improving outcomes in rats with RA.

Developing evidence-based medication therapy management tools for psychiatric nurses: An evaluative qualitative case study.

RATIONALE, AIMS AND OBJECTIVES: Clinical use of psychotropic medications involves diverse risks, addressable by nursing interventions. The research had a dual purpose: developing an "Evidence-Based Medication Therapy Management Guideline" and a "Medication Administration-Tracking Chart" and evaluating their use through an evaluative case study. METHODS: Evidence-based guideline and chart development and evaluative case study. Initially, Evidence-Based Medication Therapy Management Guideline and Medication Administration Tracking Chart for managing medication in a psychiatric unit were developed. Subsequently, their efficacy was evaluated in a case study involving 10 participating nurses used in the psychiatric unit with 123-bed of a training and research hospital in Turkey. Data was collected through personal forms, interviews, medication charts, and researcher observations, and the analysis employed Merriam's case study method. RESULTS: Three themes (inception, implementation, termination, and sustainers) and 12 sub-themes emerged. Nurses stated that the research tools filled their information gaps, enhancing the medication therapy management process's effectiveness and safety, improving nursing care quality and continuity, and benefiting patient outcomes. Nurses expressed a desire to consistently use the tools in the unit and provided suggestions. CONCLUSION: Nurses highlighted the tools' potential to enhance medication safety, psychiatric care, and patient outcomes. However, their stance on using evidence-based tools revealed an approach/avoidance conflict, balancing benefits and barriers. Experience emerged as a hindrance in embracing evidence-based clinical tools. This study is among the first to comprehensively develop evidence-based medication management guideline and administration-tracking chart for psychiatric nurses globally and in our country. Routine use of the tools is expected to enhance nurses' expertise in psychotropic medication management, leading to improved patient outcomes in medication-related aspects.

Effect of a Smartphone App (S-Check) on Actual and Intended Help-Seeking and Motivation to Change Methamphetamine Use Among Adult Consumers of Methamphetamine in Australia: Randomized Waitlist-Controlled Trial.

BACKGROUND: Interventions are required that address delays in treatment-seeking and low treatment coverage among people consuming methamphetamine. OBJECTIVE: We aim to determine whether a self-administered smartphone-based intervention, the "S-Check app" can increase help-seeking and motivation to change methamphetamine use, and determine factors associated with app engagement. METHODS: This study is a randomized, 28-day waitlist-controlled trial. Consenting adults residing in Australia who reported using methamphetamine at least once in the last month were eligible to download the app for free from Android or iOS app stores. Those randomized to the intervention group had immediate access to the S-Check app, the control group was wait-listed for 28 days before gaining access, and then all had access until day 56. Actual help-seeking and intention to seek help were assessed by the modified Actual Help Seeking Questionnaire (mAHSQ), modified General Help Seeking Questionnaire, and motivation to change methamphetamine use by the modified readiness ruler. χ2 comparisons of the proportion of positive responses to the mAHSQ, modified General Help Seeking Questionnaire, and modified readiness ruler were conducted between the 2 groups. Logistic regression models compared the odds of actual help-seeking, intention to seek help, and motivation to change at day 28 between the 2 groups. Secondary outcomes were the most commonly accessed features of the app, methamphetamine use, feasibility and acceptability of the app, and associations between S-Check app engagement and participant demographic and methamphetamine use characteristics. RESULTS: In total, 560 participants downloaded the app; 259 (46.3%) completed eConsent and baseline; and 84 (32.4%) provided data on day 28. Participants in the immediate access group were more likely to seek professional help (mAHSQ) at day 28 than those in the control group (n=15, 45.5% vs n=12, 23.5%; χ21=4.42, P=.04). There was no significant difference in the odds of actual help-seeking, intention to seek help, or motivation to change methamphetamine use between the 2 groups on the primary logistic regression analyses, while in the ancillary analyses, the imputed data set showed a significant difference in the odds of seeking professional help between participants in the immediate access group compared to the waitlist control group (adjusted odds ratio 2.64, 95% CI 1.19-5.83, P=.02). For participants not seeking help at baseline, each minute in the app increased the likelihood of seeking professional help by day 28 by 8% (ratio 1.08, 95% CI 1.02-1.22, P=.04). Among the intervention group, a 10-minute increase in app engagement time was associated with a decrease in days of methamphetamine use by 0.4 days (regression coefficient [ß] -0.04, P=.02). CONCLUSIONS: The S-Check app is a feasible low-resource self-administered intervention for adults in Australia who consume methamphetamine. Study attrition was high and, while common in mobile health interventions, warrants larger studies of the S-Check app. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12619000534189; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=377288&isReview=true.

Barriers to, and Facilitators of, Checking Drugs for Adulterants in the Era of Fentanyl and Xylazine: Qualitative Study.

BACKGROUND: Overdose deaths continue to reach new records in New York City and nationwide, largely driven by adulterants such as fentanyl and xylazine in the illicit drug supply. Unknowingly consuming adulterated substances dramatically increases risks of overdose and other health problems, especially when individuals consume multiple adulterants and are exposed to a combination of drugs they did not intend to take. Although test strips and more sophisticated devices enable people to check drugs for adulterants including fentanyl and xylazine prior to consumption and are often available free of charge, many people who use drugs decline to use them. OBJECTIVE: We sought to better understand why people in the New York City area do or do not check drugs before use. We plan to use study findings to inform the development of technology-based interventions to encourage consistent drug checking. METHODS: In summer 2023, team members who have experience working with people who use drugs conducted 22 semistructured qualitative interviews with a convenience sample of people who reported illicit drug use within the past 90 days. An interview guide examined participants' knowledge of and experience with adulterants including fentanyl, xylazine, and benzodiazepines; using drug testing strips; and whether they had ever received harm reduction services. All interviews were audio recorded, transcribed, and analyzed for emerging themes. RESULTS: Most participants lacked knowledge of adulterants, and only a few reported regularly checking drugs. Reasons for not checking included lacking convenient access to test supplies, or a place to check samples out of the public's view, as well as time considerations. Some participants also reported a strong belief that they were not at risk from fentanyl, xylazine, or other adulterants because they exclusively used cocaine or crack, or that they were confident the people they bought drugs from would not sell them adulterated substances. Those who did report testing their drugs described positive interactions with harm reduction agency staff. CONCLUSIONS: New forms of outreach are needed not only to increase people's knowledge of adulterated substances and awareness of the increasing risks they pose but also to encourage people who use drugs to regularly check their substances prior to use. This includes new intervention messages that highlight the importance of drug checking in the context of a rapidly changing and volatile drug supply. This messaging can potentially help normalize drug checking as an easily enacted behavior that benefits public health. To increase effectiveness, messages can be developed with, and outreach can be conducted by, trusted community members including people who use drugs and, potentially, people who sell drugs. Pairing this messaging with access to no-cost drug-checking supplies and equipment may help address the ongoing spiral of increased overdose deaths nationwide.